Review

pubs.acs.org/JAFC

Nanoencapsulation, Nano-guard for Pesticides: A New Window for

Safe Application
Md. Nuruzzaman,, Mohammad Mahmudur Rahman,, Yanju Liu,, and Ravi Naidu*,,

Global Centre for Environmental Remediation (GCER), Faculty of Science and Technology, The University of Newcastle, ,
University Drive, Callaghan, NSW 2308, Australia

Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), ATC Building,
The University of Newcastle, Callaghan, NSW 2308, Australia

ABSTRACT: The application of nanotechnology in pesticide delivery is relatively new and in the early stages of development.
This technology aims to reduce the indiscriminate use of conventional pesticides and ensure their safe application. This critical
review investigated the potential of nanotechnology, especially the nanoencapsulation process for pesticide delivery. In-depth
investigation of various nanoencapsulation materials and techniques, ecacy of application, and current research trends are also
presented. The focus of ongoing research was on the development of a nanoencapsulated pesticide formulation that has slow
releasing properties with enhanced solubility, permeability, and stability. These properties are mainly achieved through either
protecting the encapsulated active ingredients from premature degradation or increasing their pest control ecacy for a longer
period. Nanoencapsulated pesticide formulation is able to reduce the dosage of pesticides and human exposure to them, which is
environmentally friendly for crop protection. However, lack of knowledge of the mechanism of synthesis and lack of a cost-
benet analysis of nanoencapsulation materials hindered their application in pesticide delivery. Further investigation of these
materials behavior and their ultimate fate in the environment will help the establishment of a regulatory framework for their
commercialization. The review provides fundamental and critical information for researchers and engineers in the eld of
nanotechnology and especially the use of nanoencapsulation techniques to deliver pesticides.
KEYWORDS: nanoencapsulation, nanotechnology, agriculture, pesticide, pest control, environmental exposure

1. INTRODUCTION humidity, and temperature) inuence the extent of loss during

Nanotechnology is an emerging phenomenon that occupies an
increasingly important position in the latest range of
technologies.1 Over the past decade, it has emerged as having
the potential to revolutionize agricultural practices.2 To date,
various papers have reviewed the application of this technology
in agriculture where multifunctional approaches were ob-
served.18 The potential applications of this technology in
agricultural scenarios include seed treatment, germination, plant
growth and development, pest control, pesticide delivery,
fertilizer delivery, genetic material delivery, toxic agro-chemical
detection, pathogen detection, etc.18 In terms of agrochemical
(pesticides, fertilizers, growth hormones, etc.) delivery, nano-
scale particles have novel properties that can increase the
agrochemicals eciency and make the delivery system
smart.1 Through a smart delivery system, chemicals can be
delivered in a controlled and targeted manner that is similar to
nanodrug delivery to humans.9
Using this technology in pesticide delivery has created many
opportunities for safe application of conventional pesticides.
Commonly used pesticides are greatly limited in their
application due to a number of problems associated with
them. For example, >90% of applied pesticides are either lost in
the environment or unable to reach the target area required for
eective pest control.3,10 Around 2030% of pesticides are lost
through emissions, but this can potentially increase to 50% of
the total amount applied.11 A number of factors including
application technique, physicochemical properties of the
pesticides, and environmental conditions (e.g., wind speed,
application.11,12 The remaining losses are the result of leaching,
evaporation, deposition, being washed away, and degradation
by photolysis, hydrolysis, and microbial activity.13 The major
pathways of pesticide loss are represented in Figure 1. Given
these losses, the active ingredients (AIs) in the pesticide are
removed prior to their application and, therefore, the
concentration at the target area is well below the minimum
eective concentration.
Consequently, to achieve the desired biological response in
terms of pest control within a given period, the precise amount
that inuences nonspecic and periodic application of the
active ingredients is required.1 The repeated and indiscriminate
application of pesticides results in their being used in quantities
greatly exceeding the amount actually required to control the
target pests.3 Not only does the cost of treatment increase as a
result, but such usage ends in unfavorable outcomes either to
plants or to the environment, including soil and water
pollution,1 which ultimately poses dangers to public health.13
Such usage of pesticides increases pest and pathogen resistance,
reduces soil biodiversity and nitrogen xation, raises the
bioaccumulation of pesticides, and kills predators and
pollinators.14 It also destroys the habitats and food sources of
birds.14 Despite these side eects, their utilization is essential if
Received: November 3, 2015
Revised: December 27, 2015
Accepted: January 5, 2016
Published: January 5, 2016

2016 American Chemical Society 1447 DOI: 10.1021/acs.jafc.5b05214

J. Agric. Food Chem. 2016, 64, 14471483
Journal of Agricultural and Food Chemistry
Figure 1. Pathways of pesticide losses and degradation.
Figure 2. Promising nanoencapsulation materials used for pesticide delivery.
agricultural productivity is to be maximized. However, more
knowledge concerning the problems caused by agrochemical
pesticides for public health and wildlife has resulted in
increasingly stringent controls of their use by dierent
regulatory bodies.15
In agriculture, the development of new plant protection
formulations has long been a very active eld of research
because such problems associated with commercial pesticides
must be overcome.16 Researchers are currently designing
formulations similar to conventional formulations, but with
improved features, that is, more soluble, slower releasing, and
not prematurely degradable using the benets of materials at
nanoscale. Nanomaterials used as a pesticide or as a carrier
material have exhibited useful properties such as stiness,
permeability, crystallinity, thermal stability, and biodegradability
over commonly used pesticides.17 The nanocarrier materials
with AIs spread uniformly over the leaves and onto the soil
surface; thus, they are easily taken up by chewing insects.7 They
are also absorbed into the cuticular wax (lipid) layers of insects
via a physiosorption process and break down the water
protection barrier, resulting in insect death from desicca-
tion.18,19 The large surface area of nanopesticides increases the
anity to the target species/groups and reduces the amount of
pesticide required for pest control.20
Nanocarrier materials also protect the AIs from premature
degradation and allow them to be released in a controlled way.1
In this way pesticides can be deliberately applied using
nanodevices through adsorption on nanoparticles, attachment
on nanoparticles, encapsulated with nanomaterials, or trapped
in nanomaterials.3 Recent reviews have already concentrated on
the pesticidal ecacy of nanomaterials and their potential as a
1448
Review
carrier material.4,16,21 The available literature also suggests that
of all the delivery techniques, nanoencapsulation technology is
the most promising because it is much more ecient than any
other. Due to the wide range of potential, progress, and
possibilities of nanoencapsulation technique, this review
considers their utilization in pesticide delivery and their goals.
It is based on the available nanoencapsulation materials and
formulations as well as pest control ecacy and environmental
impact of nanoencapsulated pesticides.
2. NANOENCAPSULATION AND
NANOENCAPSULATION MATERIALS
Nanoencapsulation is the coating of various substances within
another material at various sizes in the nano-range. The
encapsulated material is commonly referred to as the internal
phase, the core material, the ller, or the ll, for instance,
pesticides. The encapsulation material is known as the external
phase, shell, coating, or membrane, for example, nanocapsules.
Attempts have been made to encapsulate commercial pesticides
as well as biocides using nanomaterials to improve their
physical properties and control the widespread use of
pesticides. Nanoencapsulation of pesticides involves the
formation of pesticide-loaded or -entrapped particles having a
diameter within the nano-range. According to the denition of
nanoparticle, this size range should be 1100 nm in at least one
dimension.22 There is still some debate about the particle size
in a colloidal system such as pesticide formulations.16 Recently,
Kah et al.16 reviewed nanopesticides as having a size ranging
between 1 and 1000 nm. Conversely, in the literature, much
evidence was found that the term nano for encapsulated
pesticides referred to a particle size of >100 nm. This may be
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due to the ecacy of their novel small-sized particulate. Grillo
et al.23 reported that the denition of nanoparticles can be
considered to be based on not only their size (<100 nm) but
also their application in medicine or agriculture where their size
may be >100 nm. However, in this review the size of
nanoencapsulated materials has been considered up to 1000
nm. Various nanomaterials have already been used to
encapsulate pesticides such as polymer-based nanomaterials,
solid lipid nanoparticles, inorganic porous nanomaterials,
nanoclays, layered double hydroxides (LDHs), etc.3 These
materials are known as nanoencapsulation materials and
encapsulate the pesticide, forming dierent types of nanoma-
terials, for example, nanocapsules, nanospheres, micelles,
nanogels, liposomes, inorganic nanocages, etc. (Figure 2).
During encapsulation, a multistage delivery pattern can be
observed as some pesticides are absorbed and attached to the
outer surface of the shell.24
2.1. Polymer-Based Nanoencapsulation Materials.
Polymers and polymeric materials have a wide range of
applications in dierent elds. For example, intense research
has been dedicated to the production of nanosized controlled
release drug formulations using dierent biodegradable
polymers.2527 Employing polymeric nanomaterials for pesti-
cide delivery is a recently developed approach.10 Generally, the
active ingredients are encapsulated with polymer, as polymer
nanocomposites (PNC) consist of a polymer that has
nanoparticles or nanollers dispersed within the polymer
matrix.28 Polymers produced by natural sources are environ-
mentally friendly and biodegradable, do not produce any
degradation byproducts, and are comparatively low cost.10 As a
result of these properties, they have proved to be suitable
encapsulation materials for active ingredients. Recently,
amphiphilic block copolymers have drawn researchers
attention in terms of their ability to form various types of
nanoparticles along with polymers. Generally, block copolymers
are obtained by the polymerization of more than one type of
monomer. Typically, the polymers should be contrasting in
nature, that is, one hydrophilic and another hydrophobic. In
this way, the block copolymers sustain their amphiphilic
properties in aqueous solution. Depending on the number of
blocks, the copolymers are known as biblock and triblock
copolymers (Figure 3). Various synthetic and natural polymers,
such as polyethylene glycol, poly--caprolactone, chitosan, and
sodium alginate, as well as the block copolymers have served to
encapsulate a wide range of pesticides through the formation of
dierent nano-range materials (Figure 4).
2.1.1. Nanocapsules. Nanocapsules are vesicular systems
that are made up of a polymeric membrane encapsulating the
Figure 3. Dierent amphiphilic block copolymers with hydrophilic and
hydrophobic blocks. Adapted and modied from ref 29.
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Review
Figure 4. Dierent morphological forms of polymeric nanoencapsu-
lated pesticides (originally adapted from ref 10 and modied).
active compounds as an inner liquid core at the nanoscale
level.26,30 The nanocapsule structure consists of a coreshell
arrangement in which the shell is composed of a polymeric
membrane or coating (Figure 5). The active substances are
usually dissolved in the inner liquid core. The inner core can
also consist of pesticide formulations or polymeric matrix, and
active ingredients may be absorbed by the polymeric shell. In
this way the active substances are encapsulated by nanocapsules
spontaneously during the formation of nanocapsules. Recently,
Ezhilarasi et al.30 documented several nanoencapsulation
techniques for encapsulating food bioactive components
through the formation of polymeric nanocapsules. It was
notable, however, that the techniques are similar to the
synthesis of nanocapsules required for encapsulating pesticides.
Polymeric nanocapsules are widely applied and, subse-
quently, intensied research studies have been conducted for
their eective synthesis. The availability of dierent polymers
and their inherent properties have given researchers the option
for synthesizing nanocapsules through dierent methods. The
most commonly developed strategies are nanoprecipitation,
emulsion diusion, solvent evaporation, double emulsication,
emulsication coacervation, and layer-by-layer deposition
(Figure 6). Nevertheless, various other methods were found
in the literature along with modications of the above-
mentioned methods, for example, melt dispersion, emulsion
polymerization, interfacial polymerization, interfacial deposition
method, solvent displacement technique, emulsion evaporation,
etc.27 However, various synthesizing methods of nanocapsules
have been described elsewhere.26,27,30,31
So far, nanocapsules synthesized using various polymers have
demonstrated their potential as an eective encapsulation
material for pesticides and biocides. A polymer such as
polyethylene glycol (PEG) has been utilized as shell material
for the synthesis of nanocapsules. Using a melt dispersion
method, Yang et al.32 synthesized round-shaped nanocapsules
of PEG loaded with garlic essential oil (Figure 7a). The loading
eciency was inuenced by the optimal ratio of essential oil to
PEG, and the loading eciency reached 80% at the essential oil
to PEG ratio of 10%. The nanocapsules retaining good
dispersion have an average diameter of <240 nm.32 A more
eective pesticide formulation of a neurotoxic organophosphate
pesticide, namely, acephate, was prepared as nanodispersion by
dispersing the nanocapsules.33 These nanocapsules were
synthesized by encapsulating the AIs with PEG-400 having a
particle size that ranged between 90 and 120 nm.33
Similarly, monomers such as methyl methacrylate (MMA)
and styrene (St) proved to be suitable for synthesizing
nanocapsules via the emulsion polymerization process. These
monomers can produce polymers such as polymethylmetha-
crylate (PMMA) and polystyrene or copolymers by the
emulsion polymerization mechanism. The emulsion polymer-
ization technique is suitable for synthesizing nanocapsules
where organic solvents and surfactants are required to prepare
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Figure 5. Dierent coreshell arrangement of nanocapsules: (left) liquid core with well dispersed active ingredients; middle) pesticide suspension as
a core; (right) polymeric matrix as a core material. Adapted and modied from ref 26.
Figure 6. Dierent synthesis methods of polymeric nanocapsules. Adapted from ref 26 and modied.
Figure 7. TEM images of nanocapsules loaded with bioactive
compounds: (a) TEM image of PEG-coated nanoparticles loaded
with garlic essential oil synthesis via melt dispersion method
(reproduced with permission from ref 32); (b) TEM image of
lansiumamide B nanocapsules synthesis via microemulsion polymer-
ization method (reproduced with permission from ref 34; copyright
2012 Chinese Academy of Agricultural Sciences, published by Elsevier
Ltd.).
the emulsion. Furthermore, an initiator (ion or free radical) is
required to facilitate the polymerization reaction. For example,
Yin et al.34 synthesized lansiumamide B nanocapsules (NCLB),
1450
Review
which were prepared by the microemulsion polymerization
method in which sodium dodecyl sulfate (SDS) as an emulsier
and N-amyl alcohol as an auxiliary emulsier were used and
azodiisobutyronitrile (AIBN) served as the initiator. The
natural active ingredient lansiumamide B was isolated from
kernels of Clausena lansium (Lour.), and NCLB were prepared
by encapsulating this active ingredient with MMA and St
(Figure 7b). The nanocapsules average size was 38.50 nm with
a spherical shape and uniform distribution and an encapsulation
eciency of >95%.34 In another investigation, Wu et al.35
synthesized natural pyrethrum-loaded nanocapsules through
microemulsion polymerization technique using the above-
mentioned monomers. They also investigated the eect of
dierent parameters (e.g., emulsier content, monomer to
pesticide ratio) on particle size and stability of the micro-
emulsion. It was reported that a perfect nanocapsule was
formed when the emulsier content was 10.6% and the ratio of
monomer and pesticide was 1:1.35 However, the major
drawbacks of this process are the nonbiodegradable nature of
the polymers, requirement of initiator, and utilization of toxic
organic solvents.27 A polymer such as poly--caprolactone
(PCL) is considered to be a good synthesis material for
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Figure 8. Assembly process of methomyl-loaded shell cross-linked nanocapsule. Reproduced with permission from ref 42. Copyright 2014 Elsevier
B.V.
preparing nanocapsules.36 This polymer is insoluble in water
and degrades slowly, and such properties have made them
suitable for pesticide delivery while remaining harmless to the
environment. Grillo et al.23 prepared nanocapsules using PCL
for encapsulating herbicides such as ametryn, atrazine, and
simazine by employing the interfacial deposition method where
the polymer was preformed in the form of a suspension. They
also prepared utilized emulsion technology for the preparation
of PCL originated nanocapsules to encapsulate the herbicide
atrazine.37 The nanoencapsulated herbicides could control the
target species, and the formulation was safe for nontarget
species. This formulation also remained stable over time and
reduced the mobility of atrazine.37 Such properties exhibited
the potential utilization of nanotechnology in agriculture.
Utilization of natural polysaccharides such as chitosan,
sodium alginate, and starch has become more popular due to
their nontoxic, biodegradable, and biocompatible properties.38
Kumar et al.39 prepared imidacloprid-loaded sodium alginate
nanoparticles by emulsion cross-linking technology. The size of
the pesticide-loaded nanoparticles ranged between 50 and 100
nm, which was conrmed by transmission electron microscopy
(TEM). The entrapment eciency was 98.66%,39 whereas in
an earlier study, Guan et al.40 encapsulated imidacloprid
microcrystals with chitosan and sodium alginate through layer-
by-layer self-assembly technique. This particular technique
oers direct surface modication of nanoengineering particles
in a colloidal system. This is a novel strategy where self-
assembly is achieved by electrostatic interactions between
polymers and sequential adsorption of oppositely charged
polyelectrolytes.41 The copolymers obtained from natural
polymers have also intensied their utilization for synthesis of
nanocapsules in current research. Synthesis of nanocapsules has
become easier due to the self-assembly nature of copolymers
and various synthesis approaches. Copolymers have the ability
to form nanocapsules through the formation of a cross-linking
polymeric network comprising an aqueous inner core. In this
way the hydrophilic pesticides can be easily encapsulated by
aqueous core nanocapsules (ACN).42 For example, Yin et al.43
synthesized nanocapsules from a new type of amphiphilic
photo-cross-linkable carboxymethyl chitosan (Az-CMCS).
Samples of Az-CMCS were obtained by mixing the
carboxymethyl chitosan (CMCS) and azidobenzaldehyde
(Az) where they linked to the amino group in the presence
of light. Later, the hydrophilic pesticide known as methomyl
was loaded into these nanocapsules. The pesticide-loaded
nanocapsules were collected from the solution through the
freeze-drying process. The mechanism of loading pesticide into
shell cross-linked nanocapsules is illustrated in Figure 8. It is
important to note that this process reduces dependence on a
surfactant, which is needed for the self-assembly of polymers.42
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Review
The amphiphilic copolymers can also form nanosize micelles
in aqueous solution, and the water-insoluble pesticides can be
solubilized in the interior region of the micelles. Finally, the
pesticide-loaded nanocapsules are obtained by a dierent
process. For instance, chitosanpoly(lactide) (chitosan-co-
PLA) grafted amphiphilic copolymers were synthesized by
reacting D,L-lactide with chitosan in the presence of triethyl-
amine in dimethyl sulfoxide solution.44 This copolymer
encapsulated the pesticide imidacloprid via the formation of
nanocapsules synthesized by the nanoprecipitation and
emulsion/solvent evaporation processes. In both processes,
copolymer to imidacloprid mass ratio signicantly aected the
particle size as well as encapsulation eciency. The larger
particle size and higher encapsulation eciency were obtained
at a lower mass ratio, where the particle size and encapsulation
eciency declined as mass ratio increased.45 A similar trend
was obtained when the organophosphate pesticide chlorpyrifos
was encapsulated into the nanocapsules synthesized by using
amphiphilic chitosan copolymer (chitosan-co-PLA-DPPE).46
The amphiphilic chitosan copolymers were synthesized by
conjugating the 1,2-dipalmitoyl-sn-glycero-3-phosphoethanol-
amine (DPPE) moiety with the chitosan-co-PLA copolymer. It
was observed that adding DPPE enhanced the loading and
encapsulation eciency of chitosan-co-PLA copolymer. The
readily available copolymer known as poly(lactic-co-glycolic)
acid (PLGA) originated from polylactic acid (PLA) and
polyglycolic acid (PGA) was used for the rst time as a
nanocarrier material in a plant protection system.46 Valletta et
al.47 encapsulated coumarin 6 with PLGA nanoparticles having
an average diameter of 3050 nm. The active compounds were
loaded into the nanocapsules using an osmosis-based method-
ology. In an earlier study, a food bioactive compound,
curcumin, was encapsulated by PLGA using the nano-
precipitation technique.48 The curcumin-loaded PLGA nano-
capsules were obtained by the freeze-drying process, and their
mean particle size was approximately 81 nm. In this synthesis
approach PEG-5000 was employed to stabilize the nano-
capsules.48
Along with copolymers the amphiphilic block copolymers
have also received special attention for synthesizing polymeric
nanocapsules. Memarizadeh et al.49 prepared amphiphilic ABA
triblock linear dendritic copolymers composed of poly(citric
acid) (PCA) as block A and PEG as block B. Utilizing this
copolymer, they directly encapsulated the pesticide imidaclo-
prid using the copolymers self-assembling ability. The average
particle size was 1020 nm but depending on the type of
solvent, time, and concentration, the morphology and size of
the nano-imidacloprid varied from ber-like to globular to
tubular and from 10 nm to several millimeters in size.49
Esmaeili and Saremnia50 synthesized polyester triblock
copolymer polyethylene glycolpolybutyleneadipatepolyethy-
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lene glycol (PEGPBAPEG) to encapsulate the plant extract
in the form of nanocapsules. The nanocapsules shell structures
were built up by the copolymers, and the olive oil served as a
core. The plant extracts were loaded into the nanocapsules
employing the polymer deposition solvent evaporation method.
They found that the nanocapsules size was aected by a variety
of factors, such as the ratio of polymer to oil, concentration of
polymers, and concentration of plant extract.50
2.1.2. Nanospheres. Nanospheres constitute the active
nanocarrier system where the active compounds are uniformly
distributed and embedded into the polymeric matrix.10,30
Although this nanoparticle can be synthesized by implementing
the methods of nanocapsule synthesis, the polymerization
technique plays the key role in the synthesis of this
nanomaterial, for example, emulsion or interfacial polymer-
ization. A schematic diagram of nanosphere synthesis is
presented in Figure 9. For pesticide encapsulation, polymers
Figure 9. Pesticide-embedded nanosphere synthesis.
such as PCL have shown their potential to encapsulate the
pesticides forming nanoparticles. For instance, Forim et al.51
encapsulated azadirachtin using this polymer, preparing nano-
capsules and nanospheres with average diameters of 150 and
200 nm, respectively. In an earlier investigation, Boehm et al.52
prepared nanospheres through nanoprecipitation using this
polymer to encapsulate active ingredients with an average
diameter of 200250 nm. Adding dierent surfactants did not
inuence the loading eciency, but they were found to be
eective for stabilizing the nanospheres containing suspensions
over 2 months.52
2.1.3. Micelles. Micelles are ideal bioactive nanocarriers for
encapsulating pesticides, especially for water-insoluble agents.
The amphiphilic block copolymers, polymers, surfactants, etc.,
play a vital role in the formation of micelles. Because of their
amphiphilic properties, the materials are able to self-assemble to
form spherical micelles in an aqueous solution by keeping
hydrophilic ends as the outer shell and the hydrophobic ends as
the core.46,53 In the case of water-soluble copolymers, the
formation of micelles can be achieved when two methods are
employed. The rst involves the direct dissolution method in
which the copolymers are simply added to the aqueous solution
above their critical micelle concentration. Hydrophobic
pesticides can be trapped in the core during the micelle
formation process. In the second, the lm casting method, lms
of copolymers with pesticides are formed and then these lms
are solubilized again using dierent approaches.54
A number of studies have tried to encapsulate commercial
and biological pesticides into nanomicellar aggregates using
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Review
PEG-originated amphiphilic block copolymers.5561 The
copolymers were synthesized from dierent weight-based
PEGs and various diesters or aliphatic diacids by chemical
and enzymatic methods.61,62 The systems design and synthetic
strategy is very exible and provides a high degree of control
over the polymer structures. This allowed tuning of the
properties of micelle disruption, the critical micelle concen-
tration, and the size of micelles. The polymer weight as well as
critical micelle concentration inuenced the radius of gyration
(Rg) of copolymers.61 The micellar characteristics depend on
the nature of the block copolymers and structures of the
hydrophilic block. The radius of gyration increased when the
size of the hydrophilic segment also increased. Recently, Koli et
al.63 synthesized PEG-based amphiphilic block copolymers
reacting with dierent molecular weights of PEG and 5-
hydroxyisophthalate having a micellar particle size ranging from
26.50 to 85.10 nm. The basic structure of chitosan was also
used for synthesizing novel amphiphilic chitosan derivatives N-
(octadecanol-1-glycidyl ether)-O-sulfate chitosan (NOSCS) to
encapsulate the pesticide rotenone.64 In this scenario,
octadecanol glycidyl ether and sulfate were the hydrophobic
and hydrophilic group sources, respectively. Due to their
amphiphilic properties, NOSCS could form polymeric micelles
by self-assembly in aqueous solution (at a size of 167.7214.0
nm) and rotenone was trapped in the NOSCS micelle solutions
using the reverse micelle method.64 In 2011, Li et al.46
synthesized a copolymer of chitosan in conjugation with
polylactide, namely, chitosan-co-(D,L-lactide) or chitosanPLA.
This copolymer was designed to achieve the amphiphilic nature
of the polymer so that the micelle structure could be easily
formed in aqueous media. The pesticide imidacloprid was
encapsulated within the core of the micelle by the nano-
precipitation method. The pesticide-loaded particle size ranged
from 259.6 to 334.6 nm depending on the weight ratio of
copolymers to imidacloprid.46 Feng and Peng65 prepared
another amphiphilic chitosan derivative, namely, 6-O-carbox-
ymethylated chitosan with ricinoleic acid (R-CM-chitosan), to
encapsulate biocides such as azadirachtin. The particle size of
the encapsulated azadirachtin(R-CM-chitosan) was reported
to be 200500 nm with a loading eciency of up to 56%.
2.1.4. Nanogels. Nanogels are aqueous dispersions of
hydrogel particles formed by physically or chemically cross-
linked polymer networks in the nanoscale size.66 In a drug
delivery system, nanogels have shown their potential as carriers
of the active compounds. This is considered to be
unprecedented for common pharmaceutical nanocarriers
because of their high loading capacity, high stability, and
responsiveness to environmental factors such as ionic strength,
pH, and temperature.6668 Such properties can be furnished as
per requirement based on the polymers and methods used for
preparing nanogels. According to Kabanov and Vinogradov,66
the methods for preparing nanogels are as follows: (i) physical
assembly of interactive polymers; (ii) polymerization of
monomers in a homogeneous phase or in a micro- or nanoscale
heterogeneous environment; (iii) cross-linking of preformed
polymers; and (iv) template-assisted nanofabrication of nanogel
particles.
Nanogels are formed through the controlled aggregation of
interactive polymers due to their self-assembly properties in
aqueous media. Water-soluble or hydrophilic polymers are
modied to create hydrophobic properties, which allow them to
interact with each other electrostatically and/or form hydrogen
bonds among themselves. The nanogels remain in a swollen
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Figure 10. (a) Physical self-assembly of nanogels in aqueous media: (i) aggregation of the hydrophobically modied polymer cholesterolpullulan in
the presence of insulin molecules results in nanogels containing entrapped protein; (ii) mixing of lauryl-modied dextran and a -cyclodextrin
polymer results in the formation of nanogels stabilized through the hostguest binding of the -cyclodextrin and lauryl moieties. (b) Chemical
synthesis of nanogels by copolymerization in colloidal environments: (i) copolymerization of monomers (1) and bifunctional cross-linkers (2) in w/
o microemulsions stabilized by surfactants (3) produces nanogels that can then be transferred into aqueous media after removal of the surfactants
and organic solvent; (ii) copolymerization reactions can also be done in o/w emulsions that can be additionally stabilized by surfactants. Reproduced
with permission from ref 66. Copyright 2009 Wiley-VCH Verlag GmbH.

condition due to the presence of an ample amount of water,
which facilitates loading of active compounds spontaneously
through electrostatic, van der Waals, and/or hydrophobic
interaction between active compounds and the polymer matrix.
In this way, the active compounds are trapped in the polymer
matrix while stable nanogel particles are formed. For instance,
Akiyoshi et al.69 and Daoud-Mahammed et al.70 investigated
the formation of nanogels and encapsulation of active
compounds (e.g., protein molecules, drug molecules) into it
through the polymers self-assembly (Figure 10a). To obtain
nanogels from polymerization of monomers, a heterogeneous
colloidal environment is required, for instance, an emulsion. In
this process, the monomers interact with each other, and
through copolymerization they encapsulate the active com-
pounds forming micelles. In the cross-linking approach,
polymerization occurs between several polymers leaving a
bioactive cross-linked chain where the active compounds are
entrapped easily (Figure 10b). In their review paper, Kah and
Hofmann21 reported that nanogels may be superior to
nanospheres because they are insoluble in water, and the active
compounds have an easy loading and release prole, whereas
Rigogliuso et al.71 claimed that nanogels tend to imbibe water
when placed in an aqueous environment and their anity to
aqueous solutions facilitates superior colloidal stability. Such
properties also promote the release of active compounds
through diusion, degradation, and ion displacement depend-
ing on level of pH and temperature.66 In addition, aggregation
can be prevented by introducing hydrophilic polymers in their
structure. Such polymers also act as a protective layer around
nanogels and prevent phase separation.
Employing nanogels as a medium to deliver pesticide is a
very recent phenomenon, and only a few studies have been
published on it. From the available literature, it was observed
that nanogels were synthesized from natural polymers, which is
a very good sign for establishing an eco-friendly approach to
pest control with the help of nanotechnology. Abreu et al.72
synthesized nanogels from a mixture of chitosan and cashew
gum to encapsulate Lippia sidoides oil. The essential oil was
loaded into the nanogels via the spray-drying method. They
reported that nanogels demonstrated a high encapsulation
1453
eciency (70%) inuenced by the polymer matrix to oil ratio,
as well as the ratios of polymer in the polymeric matrix. The
average size of the nanogels was in the 335558 nm range.72 In
another analysis, nanogels were prepared from a myristic acid
and chitosan mixture to encapsulate the Carum copticum oil.73
The oil-loaded nanogels exhibited more fumigant toxicity than
the free oil over a longer period. To increase the sustained
release of pheromones for longer periods, nanogels were
prepared from a low molecular mass gelator.74
2.2. Lipid-Based Nanomaterials. Lipid-based nanoma-
terials have been reported as potential delivery systems for
bioactive substances with better encapsulating eciency and
low toxicity.75,76 Lipid-based nanomaterials have great potential
to encapsulate the hydrophilic, hydrophobic, and lipophilic
active ingredients. They regularly facilitate the dispersion of
hydrophobic AIs in aqueous solutions and absorption of the
bioactive compounds through the cuticle of the insect body. Of
the various types of lipid-based nanoparticles, nanoliposomes
and solid lipid nanoparticles have already demonstrated their
ecacy to encapsulate pesticidal active ingredients.
2.2.1. Nanoliposomes. Nanoliposomes are the nanometric
version of liposomes, and they both share similar chemical,
structural, and thermodynamic properties.77 Along with other
applications, nanoliposomes are considered to be very ecient
in encapsulating and delivering bioactive substances to targets
of biological, biochemical, pharmacological, and agricultural
interest.78 With regard to this application, nanoliposomes
provide more surface area, increased solubility, and enhanced
bioavailability of the active compounds compared to liposomes.
They also improve the controlled release system and enable
precision targeting of the encapsulated materials.79 Generally,
nanoliposomes are vesicles consisting of a bilayer lipid with a
watery interior at nanoscale level. Colloidal structures are
formed by the arrangement of lipids, most commonly
phospholipids in an aqueous solution.80 The amphiphilic
nature of phospholipids is the key factor for developing vesicle
structure. When the phospholipids are placed in an aqueous
medium, they form an aggregated complex to defend
hydrophobic tails (acyl chain) from water molecules, whereas
the hydrophilic heads maintain a close association with aqueous
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phase. With sucient energy input, these aggregated
phospholipids rearrange among themselves and form nano-
capsules such as bilayer vesicles or nanoliposomes (Figure 11).
Figure 11. Formation of a nanoliposome.
Without adequate energy the vesicle will not form and, instead,
a at membrane-like structure will develop.81 The energy can
be supplied in various forms to achieve thermodynamic
equilibrium in the aqueous phase; on the basis of these forms
of energy inputs, various preparation methods have been
developed. The methods can be classied as mechanical and
nonmechanical.78 Some common mechanical methods are
sonication/ultrasonication, high-pressure homogenization, ex-
trusion method, microuidization, heating method, colloid mill,
and others, whereas nonmechanical methods may include
reversed-phase evaporation and depletion of mixed detergent
lipid micelles. The various preparation methods of nano-
liposomes were described elsewhere.77,78,82
Addition of other molecules such as sterols into the
nanoliposome bilayers can bring about major changes in their
properties. The most widely used sterol in the manufacture of
the lipid vesicles is cholesterol. It does not play any role in the
formation of the bilayer structure, but it can be impregnated
into the phospholipid membrane in a very high concentration
(Figure 12). For example, cholesterol can be incorporated at
Figure 12. Liposomal molecule and how the cholesterol moiety inserts
into a liposome. Reprinted with permission from ref 83. Copyright
2014 Elsevier B.V.
1:1 or even 2:1 molar ratios to phospholipids such as
phosphatidylcholine. When the optimum level of cholesterol
is present, the membrane defects of liposome can be
minimized, whereas the liposomes are prepared using long
Figure 13. Schematic representation of (a) water-soluble active compounds at the inner core of liposomes and (b) liposomes with the drug
latanoprost incorporated into the lipid bilayer (reprinted with permission from ref 94).
1454
Review
saturated acyl chains such as disteroylphosphatidylcholine or
hydrogenated soy phosphatidylcholine.76 In fact, the cholester-
ols are incorporated into the phospholipid membrane to
increase the shape stability of the liposomal vesicles by
modulating the uidity of the lipid bilayer. The impregnated
cholesterol, rst, prevents the crystallization of the acyl chains
of phospholipids and, second, provides steric hindrance to their
movement, which enhances the shape stability of the
nanoliposomes and reduces the permeability of lipid membrane
to the solutes. Moreover, the cholesterol prevents peroxidation
and acyl-ester hydrolysis of the liposome membrane by drying
the lipidwater interface.84,85 In the absence of stabilizing
agents the liposomes or nanoliposomes structures are not
stable due to their geometrical constraints.
So far, various methods have been investigated to stabilize
the nanosized liposomes to prolong their shelf life. These
include lyophilization, freeze-drying, spray-drying, and super-
critical uid (SCF) technology.8689 Of these methods,
lyophilization proved to be the best one for stabilization.90 In
this case, the phase transition can be avoided by adding
lyoprotectants. Sugars such as monosaccharides, disaccharides,
polysaccharides, or even synthetic saccharides can be used as
lyoprotectants, and among the disaccharides, trehalose proved
to be the most eective.91
Furthermore, coatings with polymers and various parameters
in the synthesis process signicantly aect size, surface charge,
dispersibility, and even encapsulation ecacy. For instance,
Bang et al.92 utilized lecithin (phosphatidylcholine) and
cholesterol for the synthesis of nanosized liposomes to
encapsulate the pesticide etofenprox. Lecithin served as an
amphiphilic compound, and cholesterol acted as a shape
stabilizer during the preparation of nanoliposomes. The
nanoliposomes were prepared by employing an ultrasonic
homogenization technique where the size of prepared lip-
osomes was reduced (up to 150 nm) by elevating the ratio of
lecithin and extending homogenization time (26 min). The
surface charge was positive (10.3 mV), whereas the liposomes
were coated with chitosan (molecular weight, 30000 Da; 0.2%,
w/v), and the low molecular weight chitosan (0.1%, w/v)
coated nanoliposomes had a lower absolute value of zeta-
potential compared to the high molecular weight chitosan
(0.1%, w/v) coated nanoliposomes. The surface charges
changed from positive to negative by a secondary coating
with alginic acid (21.8 mV). The size was also remarkably
changed in the 30 nm range after a secondary coating with
alginic acid (0.1, 0.3, and 0.5%, w/v). However, their pesticide
encapsulation ecacy declined slightly with a larger concen-
tration of chitosan (0.10.5%, w/v).92 In another study, Hwang
et al.93 reported that the size of nanoliposomes varied with the
ratio and molecular weight of coating material (chitosan).
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In terms of encapsulation, nanoliposomes are exible in
nature and able to encapsulate both hydrophilic (or water-
soluble) and hydrophobic or lipid-soluble molecules.80 During
vesicle formation the hydrophilic molecules are trapped along
with aqueous media in the inner core of vesicles (Figure 13a),
whereas the lipophilic molecules are incorporated into
liposomal bilayers (Figure 13b). Utilizing these encapsulation
mechanisms, both the water-soluble and -insoluble active
ingredients can be delivered simultaneously. This may facilitate
the application of multipesticide application (both contact and
systemic), which will combat a wide range of agricultural pests.
However, high costs, low payload, and comparatively faster
release of active ingredients are the disadvantages of this carrier
material.75
2.2.2. Solid Lipid Nanoparticles (SLNs). SLNs were
introduced in 1991 and are considered to be a promising
colloidal carrier material in controlled-delivery systems.95 In the
available literature, SLNs were reported as being a superior
carrier material relative to other nanocarrier materials such as
polymeric nanoparticles, liposomes, nanoemulsions, and nano-
suspensions in colloidal systems.9598 It has been reported that
SLNs can retain the benecial properties of other colloidal
carriers and have no disadvantages in terms of physical and
chemical storage stability, toxicity, loading capacity, production
scale, target-oriented releasing properties, feasibility, etc.96 For
the synthesis of SLNs general ingredients are required, and
these include lipids that are solid at room and physiological
temperatures, surfactant(s)/emulsier(s), and water.98 The
SLN may be either semicrystalline or crystalline, solid lipid
spherical nanostructure substances, which are stabilized by
surfactants.99 The lipid includes triglycerides, partial glycerides,
fatty acids, steroids, and waxes. The choice of emulsiers or
surfactants needed to stabilize the aqueous lipid dispersion
depends on the type of lipid utilized for the synthesis of SLN.
Various emulsiers that dier in terms of charge and molecular
weight can be used, but phospholipids may be one of the best
choices, for example, soybean lecithin or egg lecithin. A
schematic illustration of SLN structure is presented in Figure
14. Initially, the preparation of SLN began with methods
Figure 14. Schematic illustrations of SLN structure. Adapted and
modied from ref 100.
described by Samuni et al.85 To date, various methods such as
high-pressure homogenization, microemulsion, and nano-
precipitation have already been developed for the synthesis of
SLNs and described elsewhere.96,101,102 Of these methods,
high-pressure homogenization is the most commonly imple-
mented technique for large-scale production of SLNs.103 In this
particular technique two main processes are implemented as
either hot homogenization or cold homogenization. Both
methods have the same initial preparation, which includes
dispersion or dissolving or solubilization of the active
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Review
compound in the melted lipid.97 In the hot homogenization
method, a hot O/W emulsion is obtained by dispersing the
active compound loaded melted lipid into an aqueous
surfactant solution. Generally, the lipids are melted at 510
C above their melting point and passed through a high-
pressure homogenizer after dissolving or dispersing the active
compounds at the same temperature for successful emulsion
preparation. The SLNs are formed after this emulsion has been
cooled. The cooling process that leads to recrystallization of
lipid results in active compounds being trapped in the solid
lipid.
Recrystallization can also be initiated by lyophilization.95
Lyophilization is generally a promising technique to improve
the chemical and physical stability of SLNs. In the hot
homogenization process, hydrophilic active compounds are lost
to the water phase and not able to be incorporated into the
solid matrix. To overcome such problems, the cold
homogenization process can be employed. It is similar to the
hot homogenization process in that active compounds are
dispersed into the melted lipid. However, before dispersing into
aqueous surfactant solution, the melted lipids are solidied
through cooling and ground with a mortar mill. Usually, the
obtained milled lipid microparticles are dispersed in cold
surfactant solution and then homogenized at low temperature
to obtain the SLNs. The solid state of the matrix minimizes the
partitioning of active compounds to the water, but if the phase
separation occurs during the cooling process, then the active
compound enriched-shell may form, whereas the active
compound enriched-core may be obtained if the active
compounds start to precipitate rst. On the basis of the
preparation strategies and nature of formulation components,
three types of distributions of active compounds can be
observed in the SLNs, that is, homogeneously distributed into
lipid matrix or concentrated either to shell or to the core lipid
of SLNs (Figure 15).
Figure 15. Structural models for the incorporation of bioactive
components into SLNs. Adapted and modied from refs 76 and 95.
The active compound loading capacity of SLNs is aected by
various factors such as solubility of active compounds in the
melting lipid, chemical and physical structures of solid lipid
matrix, and the polymeric state of lipid material.76 The
solubility of active compounds can be increased by introducing
the solubilizers as mono- and diglycerides. Such a mixture of
glycerides with dierent fatty acids exhibits amorphous zones
processed with various chain lengths and degree of
unsaturation, which enhances the solubility of active com-
pounds and increases their loading capacity. The chemical
properties of lipid and especially crystallinity are also important
in the loading of active compounds, which can be enhanced by
utilizing such lipids to form highly crystalline particles with
perfect lattice. The crystallization process of lipids plays an
eective role in stabilizing SLN suspensions, and the
crystallization process of lipids in nanoparticles is dierent
compared to bulk lipid material. In nanoparticles the lipids are
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recrystallized at least partially in form, whereas bulk lipids are
recrystallized preferentially in form and rapidly transform
into form. Basically, the -crystalline form of nanolipid is
unstable and alters to a more stable form.104 Fathi et al.76
reported that for the production of stable SLN suspensions
delaying the polymorphic transition from to form is
required. This delay can be achieved by changing the surfactant
or fat types that crystallize prior to lipid phase.105107 Awad et
al.108 reported that polymorphic transformation from to
form can be retarded by adjusting the heating or cooling rates.
Achieving physical stability in colloidal suspension of SLNs
requires specic surface charge as well as storage at low
temperatures.109 The charged nanoparticles are prevented from
being aggregated due to electric repulsion. The surface charge
can be measured by zeta-potential and optimized by changing
the surfactant composition. Steric stability with a zeta-potential
value of >89 mV is required for their proper stabilization.
However, the application of SLNs in pesticide delivery is not
well managed and still in its infancy. Only a few studies were
found in which the pesticidal active ingredients were
successfully loaded into the SLNs. For example, Lai et al.110
prepared SLN-based pesticide formulations by applying the
high-pressure homogenization technique. The ecological
pesticide Artemisia arborescens L. essential oils were loaded
into lipid as Compritol 888 ATO and stabilized by surfactants
such as Poloxamer 188 or Miranol Ultra C32.110
2.3. Porous Inorganic Nanomaterials. The search for an
appropriate carrier material or encapsulation with suitable
properties for controlled release is a persistent theme in
pesticide application.111 In recent years the synthesis of
inorganic porous nanomaterials with interesting hierarchical
morphologies has attracted much attention because of their
potential application in a wide range of industrial and biological
pursuits. When nanotechnology was rst introduced to the
pesticide industry, research focused on producing nanosized
pesticide formulations through coatings with biodegradable
polymers. However, these polymer-coated nanopesticides suer
from various limitations such as poor thermal and chemical
stability, rapid elimination by the plant enzyme system, and
degradation of some polymers, resulting in the formation of
acidic monomers and decreased pH value within the polymer
matrix.112 Currently, their utilization is increasing gradually due
to a number of available sources, easy to modify surfaces, and
easier synthesis techniques, such as the self-assembly of
amphiphilic copolymers. In comparison to polymeric nano-
encapsulated materials (organic nanomaterials), inorganic
nanoencapsulation materials oer a nontoxic, biocompatible,
and stable alternative and have been used for controlled-release
applications.113 On the basis of the available literature, it
emerged that of the inorganic nanomaterials, porous materials
are the most signicant in terms of encapsulating bioactive
compounds. In terms of pesticide delivery, porous silica
nanoparticles are the most prominent as encapsulating
materials among the porous nanomaterials.
2.3.1. Porous Silica Nanoparticles. The synthesis of silica-
based porous materials began with the successful production of
mesoporous silica nanoparticles (MSNs), known as MCM-
41. So far, the synthesis of dierent porous silicas has advanced
rapidly for drug delivery due to their controllable morphologies,
mesostructures, and porosities, high level of biocompatibility,
and ease of fuctionalization.114 Depending on their surface
structure and interior design, porous silica nanoparticles are
grouped as mesoporous silica nanoparticles (MSNs) and
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Review
porous hollow silica nanoparticles (PHSNs or HSNs). The
pesticides are encapsulated by the MSNs or HSNs without
forming any noncovalent binding between the active
compounds and silica (SiO2) nanoparticles. This process
involves the adsorption of active compounds within the
mesopores of silica nanoparticles. To deliver the pesticide as
part of this process, the synthesis of porous silica is rst
required.
For the synthesis of MSNs, the amphiphilic surfactant
provides the basic structure on which the deposition and
condensation of SiO2 take place. The mesoporous structures in
the SiO2 are obtained by removing these surfactants (Figure
16). Various factors such as the amount of starting materials
Figure 16. Schematic of silica nanosphere formation. CPB,
cetylpyridinium bromide; TEOS, tetraethyl orthosilicate. Reprinted
with permission from ref 115. Copyright 2010 Wiley-VCH Verlag
GmbH.
and their ratio signicantly aect pore sizes, particle sizes,
morphologies, and porous structure of MSNs. The amount of
pesticide loading generally varies according to the structural
properties of MSNs. For example, Popat et al.114 loaded
pesticides such as imidacloprid into the pores of dierent
MSNs (namely, MCM-41, SBA-15, IBN-1, and MCM-48) by
simply suspending the MSNs nanoparticles in the imidacloprid
solutions for 24 h. Their investigation found that pore sizes,
morphologies, and mesoporous structures of these MSNs
aected their adsorption capacities (mg g1) of imdacloprid
(Table 1). Mesoporous silica nanoparticles with a three-
dimensional (3D) open network structure displayed a better
adsorption capacity than the two-dimensional structure where
the increased surface area enhanced pesticide loading into the
3D mesoporous structure.114 Pesticides can also be loaded into
the pores of MSNs through deposition. A pesticide can be
deposited by suspending the MSNs into the pesticide solution
following the solvent evaporation process. For instance,
Wanyika116 encapsulated a fungicide, namely, metalaxyl, by
suspending MSNs in the aqueous suspension of the pesticide
where the active compounds were deposited into the MSNs
through evaporating aqueous solvent after loading the pesticide
solution into the MSNs.
On the other hand, the templating method is the most widely
implemented method for decorating the mesoporous silica
nanoparticles with a hollow structure.117 A wide range of hard
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Table 1. Physicochemical Characteristics of Dierent Types h via SFDL, whereas 14 days was required to load only 25% wt
of Mesoporous Silica Nanoparticles and Their Adsorption with the simple immersing method.122
Capacities of Imidacloprid (Data Taken from Reference The pesticidal active compounds can also be encapsulated by
114) the porous silica nanoparticles during synthesis of HSNs.
Dierent soft templates including emulsion droplets are utilized
SBET DP VP adsorption capacity
type of MSN (m2 g1) (nm) (cm3 g1) (mg g1) to decorate the porous silica with a hollow structure. Generally,
the pesticides are dissolved into the water phase or oil phase
MCM-41 1020 2.4 1.03 3
MCM-41-Imi 754 2.0 0.50
during synthesis and then directly encapsulated into the hollow
SBA-15 505 6.5 0.84 4
interior during synthesis. Qian et al.24 encapsulated tebucona-
SBA-15-Imi 415 5.1 0.75
zole (fungicide) into the porous hollow silica nanospheres
IBN-1 919 11.0 0.86 7
during synthesis through the formation of miniemulsion, where
IBN-1-Imi 700 10.2 0.70
the emulsion droplets functioned as a soft template for the
MCM-48 1250 2.0 1.35 16
synthesis of HSNs. In addition, surface functionalization of
MCM-48-Imi 650 1.8 0.50
HSNs can be an eective tool for improving adsorption
capacity where the active compounds are absorbed by the
templates as well as soft templates have been used to generate surface of silica nanoparticles.124
hollow interior structures, whereas other additives such as 2.4. Clay-Based Nanomaterials and Layered Double
surfactants, swelling agents, or even codirecting agents play the Hydroxides (LDHs). The use of clays in agricultural and
signicant role of organizing the pore channel in the silica environmental scenarios is well-known and contributes to the
shell.118,119 In this process, initially a coreshell structure welfare of human and living organisms. Nanoclays are
develops where the template acts as the core and the shell is considered to be economically viable materials and provide
formed by condensation of silica over the core materials. great opportunities for developing multifunctional nanocarrier
Finally, HSNs are achieved by eradicating these templates and materials and their applications in life and material sciences. In
additive materials (Figure 17). For this reason the process is agricultural applications, the eects of clay materials and LDHs
are similar. Due to higher layer charge densities, strong
electrostatic forces are produced between the brucite-type
sheets and anions, which prevent LDHs from swelling and
resulting in more stable particle size than the clay minerals.125
Furthermore, several studies have investigated clay nano-
particles, indicating that functionalization of clay nanoparticles
Figure 17. Procedures for preparing porous hollow silica nano- with dierent polymers and surfactants is essential to
particles. Reprinted with permission from ref 120. Copyright 2005 manipulate the electrostatic interactions between chemical
Society of Chemical Industry. Published by Wiley and Sons. loading and the clay particles.126 In contrast, due to the positive
charge of LDHs, anionic compounds can be intercalated into
the layers of LDHs.
also known as the sacricial templating method. HSNs have a 2.4.1. Clay Nanomaterials. Nanoclays are ne-grained
vast empty space, which provides a higher loading capacity materials belonging to the wider group of minerals commonly
compared with MSNs.117 HSNs act as carrier materials for both described as naturally occurring aluminum silicates or hydrous
oil-soluble and water-soluble pesticides, and loading eciency silicates with sheet-like structures. The sheet-structured
depends on their morphological features. The pesticide loading hydrous silicates are generally termed phyllosilicates,127 which
ecacy can also be increased by improving the loading are very important because they build the structure of
methods. For example, Chen et al.121 synthesized HSNs individual clay minerals. The phyllosilicates constituted a
using the hard template as nano-CaCO3, which had a particle layered structure of two types of sheets, specically tetrahedral
size of around 100 nm and a pore size of 4.5 nm. Later they silicate and octahedral aluminum. The diversity of clay minerals
encapsulated both oil-soluble and water-soluble pesticides, depends on the arrangement of these sheets in the layer.
namely, avermectin and validamycin, respectively, in Depending on this arrangement, clays can be categorized as 1:1
HSNs.120,122 The pesticide avermectin was loaded into the type of clay (e.g., kaolinite), 2:1 type of clay (e.g.,
HSNs by employing the simple immersion method, and the montmorillonite), and 2:1:1 type of clay (e.g., chlorite). The
amount of pesticide loadings reached 58.3% (w/w).120 1:1 type of clay layer consists of one tetrahedral sheet and one
Pesticide loading by simple immersion takes longer to reach octahedral sheet, and the 2:1 type consists of two tetrahedral
the point of adsorption saturation; for example, for avermectin sheets along with one octahedral sheet, forming a sandwich-like
this process took 2 weeks. This was due to the tiny nanosized structure. The 2:1:1 type of clay is formed when one octahedral
pore in the shell of silica nanoparticles. It is expected that the sheet is added to the 2:1 type of clay. The thickness of the
open pore network and hollow interior of PHSNs will facilitate layers of primary clay particles is in the nanometer range, and
the transport of vapors and gases through the entire volume of consequently clay and clay minerals may be regarded as
the material, and pressure can be an important variable that will nanomaterials of geological and pedological origins, although
enhance the adsorption.123 On the basis of this mechanism, Liu their length varies in the millimeter range.128 For instance, the
et al.122 loaded the pesticide validamycin using the supercritical thickness of the elementary layers of smectites can vary from
uid drug loading (SFDL) process. It was observed that this 0.96 to 1.50 nm but by a few tenths to hundreds of nanometers
process improved the loading capacity and decreased the in length and width.129 However, the thickness of the
adsorption saturation period compared to the simple elementary layers varies from clay to clay minerals. The clay
immersion method. At a weight ratio of validamycin to layers are attracted by each other and may be joined together in
PHSNs of 2:1, 36% wt of validamycin was loaded within 9 a clay crystallite due to van der Waals force, interlayer cations,
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electrostatic force, or hydrogen bonding,130 leaving an
interlayer space that is known as the gallery (Figure 18). The
Figure 18. Structure of sodium montmorillonite (2:1 type) of clay
minerals. Adapted and modied from ref 131.
active compounds are mainly encapsulated into this interlayer
space or gallery. The penetration of active compounds into the
interlayer space is also known as intercalation.132
In several ways, the clay materials can interact with organic
compounds such as cation exchange, ligand exchange, hydro-
phobic interaction, hydrogen bonding, protonation, cation
bridging, and water sorption technique.133 The intercalation of
active compounds is aected by several parameters such as
exchangeable cations, distance between interlayers, and
existence of water molecules between the layers.134 Addition-
ally, the clay minerals can be modied in various ways (Figure
19). The modications of clay minerals can enrich them with
Figure 19. Dierent modied clays: (a) organoclay; (b) polymerclay
nanocomposite; (c) pillared clay; (d) heat-treated clay; (e) acid-
treated clay.
advanced properties such as specic surface area, porosity,
hydrophilic character, and charge density. Such properties may
embellish their capacity to intercalate or encapsulate the active
molecules into the interlayers more eectively.
Clay minerals can be modied as organoclay by replacing the
interlayer inorganic exchangeable cations of layered silicates
with organic cations through ion exchange reactions. Organic
cations penetrate into the interlayer space and form stable
organicinorganic compounds due to the bonding mechanism,
for example, electrostatic force between the organic cations and
charged clay layers. The van der Waals attractions between
adjacent organic species themselves along with the silicate
surface also enhance their stability.135 Extensive studies have
shown that replacement of natural inorganic interlayer cations
with selected organic cations enhanced their organophilicity
and sorptive capability and expanded the interlayer space.
Organic quaternary ammonium (R4N+X) containing alkyl,
phenyl, benzyl, and pyridyl groups is the most commonly used
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Review
cation in this process.136 Depending on the interaction between
the clay and active compounds, dierent R groups are selected
to modify these clays. To achieve proper organophilic
properties, at least 12 carbons containing the alkyl chain are
required, and this will favor the expansion of the interlayer
space.135 For example, in montmorillonite the interlayer space
expanded 23 nm while modied with dierent alkyl-
ammonium.137 The maximum expansion or swelling occurs
when the organic liquids possess high polarity and high
organophilic characteristics. In the case of low-polar hydro-
carbons the inlayer spaces expand through utilizing small
amounts of polar compounds such as alcohol, esters, or
aldehyde. With this mechanism a wide range of organic
compounds is intercalated into the organoclay minerals. The
expanding interlayer spaces also facilitate the intercalation of
neutral organic compounds due to their organophilic environ-
ment.135
The clay or organoclay minerals can also be modied with
polymers forming polymerclay nanocomposites. Depending
on the state of layered silicates, polymerclay nanocomposites
are formed as conventional nanocomposites, intercalated
nanocomposites, and exfoliated nanocomposites (Figure 20).
Figure 20. Three idealized structures of polymer/layered silicate
composites with their WAXD patterns and TEM images. Reprinted
with permission from ref 138. Copyright 2006 Indian Academy of
Sciences.
X-ray diraction (XRD) patterns and associated basal spacing
can give an idea about the state of nanocomposites. In a
conventional nanocomposite the polymers are unable to enter
the interlayer space and the basal spacing remains unchanged.
However, when the polymers are intercalated, the basal spacing
increases. In the case of exfoliated nanocomposites the XRD
fails to determine the basal space. However, the formation of
polymerclay nanocomposites is inuenced by their prepara-
tion methods. Chen et al.139 reported that exfoliated nano-
composites are mainly synthesized via the in situ polymer-
ization and solution method, whereas it is easier to synthesize
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intercalated nanocomposites with the melt processing method.
For instance, a molten low-polar polymer such as polystyrene
can be directly intercalated into the alkyl-ammonium modied
smectites.140 Coexisting exfoliated and intercalated nano-
composites can also be observed.
Some other methods of polymerclay nanocomposite
formation may be covulcanization, solid state intercalation,
solgel, emulsion, supercritical CO2 uid methods, and
others.139 When the polymers are derived from a natural
source such as starch, cellulose, or their derivatives, such as
chitosan and gelatin, the composites are termed bio-nano-
composites. The biopolymers are considered to be eco-friendly
polymers and can be used as an alternative to conventional
polymers for environmental application. They are able to
synthesize the nanocomposites similarly to conventional
polymer. For example, Chevillard et al.141 prepared new
pesticide formulations combining Ethofumesate (model
pesticide) and polymerclay nanocomposites via the bi-vis
extrusion process. The nanocomposites were designed with
wheat gluten and three montmorillonites (MMT), that is,
unmodied MMT (HPS) and two surfactant-modied MMTs
(C30B and D72T). In their investigation, well-dispersed
nanoclays were observed in TEM pictures (Figure 21), which
indicated that wheat gluten was able to interact with modied
and unmodied MMT, and a well-intercalatedexfoliated
nanocomposite structure was formed.141
Figure 21. TEM pictures of wheat gluten-based materials containing
Ethofumesate lled with unmodied MMT (WG-HPS-E) and
organically modied MMMT (WG-C30B-E and WG-D72T-E).
Reprinted with permission from ref 141. Copyright 2012 Elsevier
Science B.V.
The hydrophilic properties of the clay minerals surface can
be achieved through hydration of exchangeable cations and in
the presence of SiOH clay mineral groups. When water is
absent, the clay minerals have a higher anity to the
hydrophobic compounds.138 The hydrophilic surface of the
clay minerals can become hydrophobic during the modication
of clay minerals as pillared clay with a suitable pillaring agent.
Both the inorganic and organic compounds can be used as a
pillar. The pillared clays can be prepared according to a simple
procedure of replacing exchangeable cations (Ca2+ or Na+) into
the interlayer space with large polyoxocations of a multivalent
metal such as Al, Si, Cr, or Zr in which the platelets are
separated from each other by hydroxy-oxides pillars. In this
way, the pillared clays possess a porous structure with a high
surface area.142 In their analysis, Gerstl et al.142 prepared
pillared clay modifying the sodium montmorillonite with
Al(OH)x, and the herbicide alachlor was successfully loaded
into the interlayer of pillared clays.
The clay materials can also be modied with heat treatment
or acid treatment. Bojemueller et al.143 investigated the
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morphology of thermally modied bentonite and its interaction
with pesticide. They found that the mesopore (diameter = 2
50 nm) volume of calcinated bentonite increased above 450 C,
whereas the micropore volume decreased. They also mentioned
that pesticide molecules interact with aluminum ions or
oligomeric hydroxoaluminum cations, which enriched at the
edges of the silicates due to the heat treatment.143 The
depopulation of octahedral sheets and amorphous silica was
observed, whereas clay minerals were treated with acid.
Increased surface area, high porosity, and acidic characters
were also noted in acid-treated clay minerals. In their
investigation, Fernandez-Perez et al.144,145 obtained better
pesticide formulations of diuron and carbofuran when natural
and acid-treated bentonite were incorporated into the
formulations. The properties of modied clays and sub-
sequently their applications strongly depend on the structural
arrangement of those nanohybrid materials and the mecha-
nisms involved in the clayorganic interactions. Despite their
availability in nature, utilization of commercially available
surface-modied clay minerals and in particular montmor-
illonite is common in application-based research. In their
review paper, Majeed et al.127 documented several commer-
cially available clay minerals along with surface modiers.
Various methodologies have been established for synthesizing
clay materials such as the solgel method, microemulsion
method, layer-by-layer deposition method, sonication techni-
que, and others.148 Nevertheless, both natural and synthetic
clay nanoparticles suer from crystalline impurities and require
time-consuming preparation to remove them. However, more
investigation is required on how to improve synthesis
procedures. The properties of clay minerals can be modied,
and they may synthesize more clay nanomaterial eectively
with improved features and morphology. Such clay nanoma-
terials may ourish when they are applied to pesticide delivery
in the near future. For instance, Lvov et al.147 derived halloysite
clay nanotube with an average diameter of 50 nm, length of 500
nm, and a 20 nm diameter hollow inner core (Figure 22).
Halloysites are economically viable and on the basis of toxicity,
biocompatibility, and availability, they are a promising nano-
material compared to carbon nanotubes.146 However, their
application as a nanoencapsulation material for pesticide
delivery requires further investigation.
2.4.2. Layered Double Hydroxides. LDHs are natural and
synthetic materials of anionic lamellar compounds made up of
positively charged brucite-type layers of mixed metal
hydroxides.149,150 Their positively charged layer structure
exhibits a variety of stacking faults that generate many dierent
polytypes, which are characterized by a wide chemical
composition range.125 The hydroxide ions connect with each
other and play the key role of forming innite two-dimensional
nanosheets with a thickness of around 1 nm and a lateral size
ranging from sub-micrometer to several tens of micrometers.
The hydroxide ions remain at the vertexes of the shared
octahedral where the metal cations occupy the central position
(Figure 23). The generic formula of LDHs has been
represented in the literature as [M2+1xM3+x(OH)2][An]x/n
zH2O, where M2+ and M3+ denote cations such as M2+ = Mg2+,
Zn2+ or Ni2+ and M3+ = Al3+, Ga3+, Fe3+, or Mn3+; An is a
nonframework charge compensating inorganic or organic
anions, for example, CO32, NO3, Cl, SO42, or RCO2;
and x is the mole fraction of M3+.150152 LDHs are considered
to be multifunctional nanomaterials153155 and have several
attractive features, for instance, tunable properties in layer
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Figure 22. (a, b) TEM images of halloysite nanotubes dispersed in water. SEM image of (c) layer-by-layer nanocoating with (PEI/halloysite)3
multilayer (top view) and (d) halloysite nanotube coated with PEI/PSS + (PEI/7 nm silica)2 shell. Reprinted with permission from refs 146 and 147.
Copyright 2002 Elsevier. (e) SEM cross-section view of the PEI/PSS/PEI + (halloysite/PEI)2 + (PEI/silica/PEI/halloysite)3 multilayer and (f)
TEM image of the halloysite G tubule cross section. Reprinted with permission from ref 147. Copyright 2002 Elsevier.

Figure 23. Schematic representation of the structure of layered double

hydroxides (LDHs). Reproduced from ref 150 (open access journal).

charge density, particle size, and morphology.150 They also

possess good biocompatibility and low toxicity. Along with
these features, their easy synthesis methods have drawn
attention to their use as a nanocarrier material in drug delivery
systems.150 To date, various methods have been developed for
synthesizing nanosized LDH sheets or platelets based on
delamination or top down and controlled nucleation or
bottom up approaches.151 However, size, shape, and
morphological features with corresponding synthesis methods
have been reported elsewhere.154,156 Several methods have also
been established for loading active compounds or biomolecules
into the interlayers of LDH nanosheets, which can be expressed
as LDHnanohybrids/nanocomposites.150,152,157 Some of the
more promising routes are depicted in Figure 24. Dierent
drug-loading methods used for encapsulating or intercalating
the drugs for the synthesis of drugLDH nanohybrids/
nanocomposites have advanced their utilization in agriculture,
especially in agrochemical delivery systems.
The development of controlled/slow-release pesticide
formulations utilizing LDHs is a recent phenomenon. Their
high buering capacity, high water retention ability, acid-
neutralizing potentials, and high anity to ubiquitous carbonate
ions may facilitate the preparation of complete and controlled-
1460
Figure 24. Dierent ways to incorporate active compounds into LDH
nanomaterials. Adapted and modied from refs 152 and 157.
release intercalated pesticide formulations. The soil compatible
nature of LDHs makes them good candidates for pesticide
delivery and serves as a matrix for encapsulating or entrapping
the pesticide. In their investigation, Cardoso et al.158
intercalated anionic herbicides 2,4-D, MCPA, and picloram
into MgAl-LDH using three dierent routes as direct synthesis
(SD) by the coprecipitation method, regeneration method
(RE), and ion-exchange method (IE). The basal spacing
obtained from powder X-ray diraction (PXRD) patterns of
LDHherbicide complexes indicated their structural dier-
ences synthesized via dierent methods (Table 2). The basal
spacing may vary depending on the surface charge density.
However, the amounts of intercalated pesticide were similar for
each synthesis method.158 LDHs were also found to be eective
for encapsulating the natural bioactive compound. Park et al.159
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Journal of Agricultural and Food Chemistry
Table 2. Basal Spacing () of LDHHerbicide Complexes
Prepared with Three Dierent Methods (Data Taken from
Reference 158)
synthesis method
direct synthesis regeneration ion exchange
sample (DS) (RE) (IE)
2,4-DLDH 19.02 19.36 19.42
MCPALDH 18.43 19.19 19.24
picloramLDH 16.72 16.44 16.35
evaluated the potential of LDHs as an encapsulated material for
a natural antibiotic, cinnamate, which also serves as a fungicide.
Cinnamate was intercalated using the coprecipitation method,
where the intercalated amount was 42 wt %.159
2.5. Other Nanoencapsulation Materials. Besides the
above-mentioned nanoencapsulation materials, other nanoma-
terials have the potential to be eective carriers for pesticide
delivery, for instance, poly(citric acid) grafted carbon nano-
tube.160 On this theme, nanoencapsulation materials used for
drug delivery and bioactive food ingredients indicated their
potential to be eective carriers for pesticide delivery as well.
Some potential nanoencapsulation materials are polymer-
somes,161 nanostructured lipid carriers,75,76,97 niosomes,162
dendrimers,163 and inorganic porous materials such as porous
nano-CaCO3,164,165 nano-zeolite,166 and so on.
3. NANOENCAPSULATED PESTICIDE FORMULATIONS
Pesticide formulation is a complex term indicating a mixture of
dierent materials such as active ingredients, solvents, surface
active ingredients, and stabilizers. Of these materials, the active
ingredients are responsible only for controlling target pests,
whereas other materials such as dierent organic solvents,
surface active ingredients (stickers or spreaders), and stabilizers
help maintain their solubility and stability and improve their
pesticidal activity (http://npic.orst.edu/topicfact.html). The
materials other than active ingredients are collectively known
as inert ingredients. Conventional pesticides are formulated as
follows: emulsiable concentrates (ECs), ready-to-use low-
concentrate solutions (RTU) and ultralow-volume concentrates
(ULV), suspension concentrates (SC), soluble concentrates
(SL), microencapsulates (ME), soluble powders (SP or WSP),
wettable powders (WP), water-dispersible granules (WG),
dusts (D), pellets (PE), granules (GR), tablets (TA), baits
(BA), gels (GE), dry owables (DF), aerosol (A), etc.167 On
the basis of the nature and properties of these formulations,
they are applied directly or processed as a solution, suspension,
or emulsion prior to their application.
Safer and more convenient pesticide formulations are basic
requirements, and this remains a controversial issue. Seaman168
reviewed the trends in the formulation of pesticides and noted
that ECs and WP are no longer accepted by farmers and
registration authorities. Conversely, suspension concentrates
are now commonly used in practice. The author also asserted
that water-dispersible granules and emulsions in water are
receiving increasing attention, as capsule suspensions and
polymeric surfactants work better and more safely in favorable
cases, allowing microencapsulation to occur.168 Because the
droplet sizes are larger, microencapsulated pesticides retain
poor stability after dilution, and the controlled release of
pesticides is aected by their wide shell thickness.16,169 In
recent years, pesticides have been formulated more eciently
with the help of nanotechnology. Such formulations have much
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better potential than microencapsulation. Currently, intensive
research studies are developing a variety of nanoencapsulated
pesticide formulations such as microemulsions, nanoemulsions,
and nanosuspensions to avoid the disadvantages of available
commercial pesticides. So far, several commercial brands of
encapsulated pesticide formulations (Primo MAXX, Banner
MAXX, Subdue MAXX, Apron MAXX, etc.) are commercially
available on the market manufactured by some world-leading
pesticide companies such as BASF, Bayer Crop Science, and
Syngenta.16 In the previous section we noted dierent
nanoencapsulation materials that were successfully used to
encapsulate the active ingredients. In this section, we focus on
dierent liquid-based or colloidal nanopesticide formulations in
which the active ingredients have been formulated in the
nanoscale range through encapsulation using dierent surface
materials.
3.1. Microemulsion. In pesticide formulation, micro-
emulsions are considered to be optically transparent or
translucent dispersions of pesticides either in water or in oil
and solubilized by additives such as surfactant. This system
belongs to the isotropic solution of two immiscible liquids,
where they are dispersed and stabilized by the interfacial lm of
an appropriate surfactant or mixture of surfactants with droplet
sizes smaller than 100 nm.170173 Various size ranges have been
reported in the literature, and microemulsions consist of three
basic components: oil, surfactants, and water.174 Mixtures of
these components can be arranged in dierent ways and form
various phases such as water continuous, oil continuous, or
bicontinuous phases (Figure 25). These phase formations
Figure 25. Schematic representation of the three most commonly
encountered microemulsion microstructures: (a) oil-in-water; (b)
bicontinuous; (c) water-in-oil microemulsion. Reprinted with
permission from ref 175. Copyright 2012 Elsevier B.V.
depend on their composition, especially with reference to
concentration, nature, arrangement of the molecules, and
environmental condition.176 Generally, the term used is
microemulsion (O/W microemulsion) when the oil phase is
dispersed into the water phase, whereas the term reverse
microemulsion (W/O microemulsion) is employed to indicate
opposite phase dispersion. No high-energy input is required for
forming a microemulsion; rather, the microemulsions are
formed spontaneously by the action of appropriate surfactants
or emulsiers when these phases are brought into contact
under gentle stirring.177,178 The surfactants are amphiphilic in
nature and comprise a polar headgroup and an apolar tail
region. When surfactants are introduced into immiscible
mixtures of oil and water, the surfactant molecules can locate
at the oil/water interface and may form a monolayer by
dissolving hydrophobic tails in the oil phase and the hydrophilic
head groups in the aqueous phase. On the basis of this
mechanism, in recent times microemulsion preparations using
block copolymers have drawn attention for their utility as
alternative types of surfactants. In addition, cosurfactants have
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been commonly implemented in microemulsion techniques.
Cosurfactants are also amphiphilic in nature and able to
improve the partitions to an appreciable extent in the surfactant
interfacial monolayer or microemulsion region.178 Several
molecules function as a cosurfactant, for example, nonionic
surfactants, alcohols, alkanoic acids, alkanediols, and alkyl
amines.176 For instance, Zhao et al.179 used methanol as a
cosurfactant during the preparation of a microemulsion
formulation of cyhalothrin. Microemulsions are thermodynami-
cally stable, and this depends on a particular range of
compositions and environmental conditions.180 Determining
the best proportions of each ingredient is a challenging task,
and there is no general theory for predicting microemulsion
structure in a particular system of oil, water, and surfactant.172
Nevertheless, in several investigations, pseudoternary or tertiary
phase diagrams have been constructed to determine the
acceptable concentration ratio of dierent phases.173,181183
In the ternary system of microemulsions, two immiscible phases
(water and oil) are present with a surfactant (Figure 26). The
Figure 26. Hypothetical pseudoternary phase diagram of an oil/
surfactant/water system emphasizing the microemulsion and emulsion
phases. Existence elds are shown where conventional micelles, reverse
micelles, or water-in-oil (w/o) microemulsions and oil-in-water
microemulsions are formed along with bicontinuous microemulsions.
At very high surfactant concentrations two phase systems are observed.
Reprinted with permission from ref 175. Copyright 2012 Elsevier B.V.
increased isotropic monophasic area in the phase diagram gives
an idea of acceptable concentrations of dierent phases.173 The
concentration of the dispersed phases should be small enough
relative to the continuous phase to avoid droplet interactions,
as well as bicontinuous phase formation.
Microemulsion has the potential for encapsulating both
hydrophilic and hydrophobic active compounds.184 Pesticides
are loaded into the dispersed phase of microemulsion
formulations, and phases are determined depending on the
nature of pesticides. For example, Feng et al.183 prepared a
microemulsion formulation of chloropyrifos dissolved in ethyl
acetate (acting as oil phase). A microemulsion system is also a
prospective medium for the delivery of natural pesticidal
essential oils. In one study, for instance, Xu et al.182 prepared an
O/W microemulsion of neem oil using a mixture of neem oil,
emulsier system, and water. Microemulsion formulations of
pesticides are much more ecient than conventional pesticide
formulations such as emulsions, ECs, and WP. Compared to
other formulations microemulsion formulations provide better
stability, low viscosity, and better permeability and solubility as
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well as formulations free of toxic organic solvents (e.g., xylene,
toluene).178 Despite these advantages, however, this system
suers from some problems such as requiring large amounts of
surfactants, low pesticide active ingredient concentration, and
instability of the preparation and diluted system during
storage.172,173 Moreover, it is prone to disintegration when
changes occur in environmental conditions.185
3.2. Nanoemulsion. In recent years various pesticides have
been encapsulated using nanoemulsion technology to avoid the
disadvantages of microemulsion. There are no dierences in the
basic structure of microemulsion and nanoemulsion, even the
size of droplets overlap with each other, but the signicant
dierences are equilibrium status and amount of surfactant
being used.75 As microemulsions, nanoemulsions are also a
mixture of two or more immiscible liquid phases; perhaps the
simplest example of this is oil and water, but it exists in a
nonequilibrium colloidal system.186 In a nanoemulsion, one
liquid is dispersed as small spherical droplets into another liquid
but required a lesser amount of surfactants (510%) than the
microemulsions (20%).21 The term nanoemulsions is also
reported as mini-emulsions, ultrane emulsions, and sub-
micrometer emulsions by Song et al. (ref 187 and references
therein). Mason et al.186 tried to dierentiate between these
terms on the basis of droplet size. Song et al.187 preferred the
term nanoemulsion to suggest droplets nanoscale size range,
typically from 20 to 200 nm. This is concise and avoids
confusion with the term microemulsions. In his review paper,
McClements176 focused on the dierences and similarities
between nanoemulsions and microemulsions. The author
reported that the most fundamental way of dierentiating
them depends on their stability mechanism.175 Basically,
microemulsions are thermodynamically stable, whereas nano-
emulsions are thermodynamically unstable rather than kineti-
cally stable.175 To achieve kinetic stability, high-energy inputs
are required.186 High energy can be applied by using a high
shear stirrer, high-pressure homogenizers, microuidizers, and
ultrasound generators.188 These high-energy input methods are
suitable for small-scale production scenarios, but may be
dicult to scale-up for large commercial agrochemical interests.
Research analyses were conducted to develop reproducible low-
energy emulsication or self-emulsication methods such as
spontaneous emulsication method and phase inversion
temperature (PIT) method, which have been discussed
elsewhere.189191 For example, Porras et al.172 prepared W/O
nanoemulsions using a low-energy emulsication method and a
magnetic stirrer operating at approximately 700 rpm at 35 C
with droplet sizes as small as 30 nm.
However, the formation of nanoemulsions that remain stable
over a signicant period of time is an important yet challenging
property. The precise mechanisms by which nanoemulsions
form and how properties can be controlled remain the subject
of intensive basic research. Nanoemulsions have much better
gravitational separation and aggregation compared to conven-
tional emulsions.185 The other physicochemical mechanisms
that break down nanoemulsions are Ostwald ripening,
occulation, and coalescence. A number of factors must be
controlled to make a stable nanoemulsion formulation; for
example, appropriate composition of the components, order of
the addition of components, and application of the shear or
surfactants in a manner that eectively ruptures droplets.186 In
nanoemulsion the dispersed phase should fulll some other
requirements. Molecules should be insoluble in the continuous
phase to avoid Ostwald ripening. The LSW (Lifshitz-Slezov and
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Wagner) theory expresses the Ostwald ripening rate through
the equation (eq 1):172,192
drc3 8C( )VmD
= =
dt 9RT (1)
where rc = the critical radius of the system at any given time,
C() = the bulk phase solubility, = the interfacial tension, Vm
= the molar volume, D = the diusion coecient in the
continuous phase, = the density of the liquid (continuous
phase), R = the gas constant, and T = the absolute temperature
It was reported that nanoemulsions generally exhibit good
stability without phase separation during weeks when droplet
size slightly increases with time.193 This may be due to the
breakdown of the process known as coalescence. If coalescence
is the driving force for instability, the droplet size changes over
time, as per the following equation (eq 2)172
1 1 8 molecules into solid particles with a bottom-up process.199
= 2 t
r 2
r0 3 (2)
where r = the average droplet size after t, r0 = the value at t = 0,
and = the frequency of rupture per unit of surface of lm.
The continuous phase should have a signicant excess of
surfactants that allow the new surface area to be rapidly coated
with nanoscale droplets, thereby inhibiting the shear-induced
coalescence. Stability also depends on applying a suitable
stabilizer and surfactant used in the formulation. The utilization
of a surfactant may strengthen the droplets and ensure the
nanoemulsion systems kinetic stability during storage. Droplet
size is a function of the ratio of oil and surfactant weights in an
oil-in-water nanoemulsion system. The initial water concen-
tration for dierent oil/surfactant ratios also aects the droplet
size. Wang et al.192 reported that more stable nanoemulsions
were obtained with higher surfactant concentrations. Some-
times a mixture of surfactants provides better stability than the
single surfactant. The emulsiers or surfactants act as a shear,
which breaks down a dispersible liquid into small droplets
(typically a few nanometers in size). This process is known as
emulsication, where surfactants reduce the surface tension and
precipitation is no longer likely to occur. Nanoemulsions are
good candidates for delivering poorly water-soluble active
ingredients. However, both hydrophilic and hydrophobic
pesticides can be dispersed and encapsulated by preparing
nanoemulsion formulations that increase the bioavailability of
active ingredients.
3.3. Nanosuspension. Briey, nanosuspensions are the
dispersion of solid nanoparticles in a liquid. Nanosuspension
also refers to the term nanodispersion.16,194 To date, intensive
work has been done on preparing and investigating suspension
formulations in drug delivery, but only a few studies have been
published on pesticide formulations. Nanosuspension is mainly
a sub-micrometer colloidal dispersion of the drug particle that is
stabilized by surfactants, or a polymer, or a mixture of both.195
In agriculture, this technology facilitates the dispersal of poorly
water-soluble solid pesticides (powder, dust, nanocapsules, etc.)
in aqueous media while maintaining their stability. As a result,
the bioavailability of pesticides can be increased. Although
nanosuspensions are not truly linked to nanoencapsulation, it
plays a vital role in the delivery of nanoencapsulated pesticides,
especially those that are poorly soluble in water. This may be an
eective route for those microemulsion and nanoemulsion
formulations from which nanocapsules or dry nanoparticles
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loaded with pesticides can be obtained, resulting in longer
stability.
For example, Elek et al.196 synthesized nanopowders of the
pesticide novaluron by directly converting O/W micro-
emulsions containing pesticide and volatile solvents into
powders where the pesticides were encapsulated with sodium
dodecyl sulfate (SDS). The nanopowder was redispersed in
water as a nanoemulsion formulation after drying, where the
particle size was 200 nm by DLS and 30100 nm viewed by
cryo-TEM.196 Similarly, Zeng et al.197 prepared a nano-
suspension of -cypermethrin by dispersing encapsulated AIs
in water. Recently, Saini et al.198 prepared a nanosuspension
formulation of a newly reported pesticide, pyridalyl, in which
the nanocapsules of alginate-pyridalyl were synthesized via the
O/W emulsication process.
Moreover, nanosuspensions can be obtained either by
reducing the particle size of larger crystals to the nanosize via
a top-down approach or by the precipitation of dissolved
With these processes, the pesticides are directly dispersed as
suspension formulations in the nanosize range where the
pesticides are encapsulated as nanomicelles (Figure 27). Strom
Figure 27. Nanosuspension synthesis process (adapted from ref 200).
et al.194 prepared nanodispersion formulations of several
pesticides such as triazole, spinosad, and atrazine using the
wet milling process. The stability of a nanosuspension is
remarkable because it protects against Ostwald ripening.
Stabilizers play a vital role in maintaining adequate stability in
a nanosuspension. Verma et al.201 investigated the stability of
indomethacin under dierent stress conditions. They reported
that an increase in the particle size was attributed to Ostwald
ripening, but an increase in the amount of micellar solubilized
active compound had no signicant eect on the ripening
rate.201 The increased stabilizer concentration reduced the
particle size due to interference of the stabilizer layer at the
interface with both dissolution and growth at the nanoparticle
interface.
4. GOALS OF NANOENCAPSULATION AND THEIR
OUTCOMES
A successful modern crop protection chemical should have
several properties, including the ability to remain active or
survive in the spray environment (sun, heat, rain); to be taken
up into the target organism (e.g., fungus, insect) eectively; to
resist the defense of the pest and pathogen; to remain benign to
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Figure 28. Goals of nanoencapsulation in pesticide applications (reproduced from ref 204).
plants, humans, and other mammals; to preferably possess a
new mode of action; and, nally, to provide economic
returns.202 Currently, available pesticides and biocides are
unable to maintain these properties, resulting in repeated
application, increased production costs, and ultimately the
environment being more polluted. Nanoscale carriers or
nanoencapsulation materials can enhance the bioavailability of
active substances and reduce toxicity, improving the timed
release of active substances and enabling the precise targeting of
active substances by encapsulating the bioactive compounds.203
Nanoencapsulation technology has been introduced in crop
protection chemicals to achieve either of these outcomes, or
being nanosized, which reduces the amount being applied
(Figure 28). So far, several studies have investigated the
outcomes of nanoencapsulation for achieving the goals of a
successful pesticide formulation (Table 3). Although the goals
of nanoencapsulation are inter-related, the major goals can be
expressed as
increased controlled-release properties of the pesticide,
increased solubility of active ingredients,
protection against premature degradation, and
increased stability of the pesticide.
4.1. Controlled Release of Active Ingredients. The
undesirable environmental eects resulting from applying
conventional pesticide formulations to control pests have
made people more wary of using controlled-release (CR)
technology for pesticides.216 CR formulations regulate the
supply and release of AIs required for eective pest control.224
In this way, CR formulations reduce the amount of pesticides
being applied; that is, smaller concentrations of such chemicals
are being introduced into the environment.224 The application
of nanotechnology in the production of CR formulations and
the search for an appropriate carrier material for active
substances for controlled release are very important research
areas.16
4.1.1. Controlled-Release Mechanisms. Conventional pes-
ticide formulations contain AIs that get released immediately
after application. As a consequence, these ingredients are short-
lived and diminish from the system rapidly. For this reason,
such a releasing system of AIs may be termed as rapid release.
Consequently, to maintain their period of optimum availability
(POA) required for eective pest control, repeated applications
are required. In contrast, in terms of nanoencapsulated
pesticides, the release of bioactive ingredients from the
encapsulation materials can be mechanized in two ways, that
is, sustained release and delayed release (see Figure 29).
Sustained release is a mechanism whereby nanoencapsulation
materials are engineered so that active ingredients are
constantly released. In this system the half-release time (t1/2)
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and POA of AIs are extended. As a result, the nanoencapsulated
pesticides can control pests for a longer period of time.
Depending on the nature and properties of nanoencapsulation
materials as well as AIs, various types of releasing systems are
found in sustained release such as diusion, dissolution,
erosion, swelling, and ion exchange. On the other hand, in
delayed release, the active ingredients are released after a
certain period, which may be termed lag time. Once the
release starts, it is no longer obstructed and total release of
active ingredients persists over a given period of time. Such a
type of release is also known as burst release.
4.1.2. Factors Aecting Controlled Release. Controlled
release of AIs is aected by the physical properties of
nanoencapsulation materials. Several variables such as types
of nanoencapsulation materials, shape and dimensions, poly-
morphism, shell thickness, porosity, encapsulation eciency,
and amount of encapsulate load, related to nanoencapsulation
materials, signicantly aect the controlled-release system.
Controlled release of AIs is also inuenced by their release
environment. The physicochemical properties of nanoencapsu-
lation materials depend on several release environmental factors
such as pH, ionic strength, and temperature. Several studies
have already been carried out to synthesize controlled-release
nanoencapsulated pesticide formulations using various nano-
encapsulation materials or colloidal formulations (described
earlier). However, factors that inuence the controlled release
of nanoencapsulated AIs are described in more detail below.
4.1.2.1. Controlled Release of AIs from Polymer-Based
Nanoencapsulation Materials. Researchers from India have
developed controlled-release formulations (CRFs) for a
number of commercial pesticides and biocides by encapsulating
them using PEG and PEG-originated amphiphilic copoly-
mers.55,57,58,60,61 CRFs of dierent pesticides were developed in
the form of nanomicellar aggregates. Shakil et al.61 investigated
the controlled release of carbofuran from nanomicellar
aggregates. They reported that the release half-life of carbofuran
in aqueous media ranged from 7.5 to 55.0 days depending on
the polymer matrix, whereas for a commercial granule pesticide,
it was only 3.2 days. The maximum concentration of AI was
obtained between 21 and 49 days from encapsulated pesticides,
whereas in the case of commercial carbofuran, the maximum
concentration was found on the seventh day and after that the
AI content decreased rapidly. In the case of the molecular
weight of polymers, carbofuran release was faster from PEG-
600-based formulations than from PEG-1800-based formula-
tions.61 This outcome indicates that the release of AIs can be
adjusted by changing the molecular weights of polymers.
Similar results were reported in the investigation of release
kinetics of encapsulated imidacloprid,55 -cyuthrin,58 and
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 Table 3. Improved Properties of Nanoencapsulated Commercial Pesticides and Biocides
Sl nanoencapsulation
no. encapsulation material pesticide/biocide material/form improved features achieved due to nanoencapsulation refs
Commercial Pesticides
A Synthetic Polymer/Polyesters
1 polyethylene glycol (PEG) carbofuran nanomicelles applications of the AI can be optimized to achieve insect control for the desired period depending on the matrix of the 61
originated block copolymers polymer used
imidacloprid nanomicelles in water, release of AI was faster in commercial formulation than in the developed CR formulations 55
imidacloprid nanomicelles CR formulations of imidacloprid exhibited significantly better control of pests compared to its commercial formulations 205
-cyfluthrin nanomicelles slow release of the AI compared to commercial pesticide formulations and application rate of -cyfluthrin can be 206
optimized to achieve insect control at the desired level and period
carbofuran nanomicelles under field conditions, developed CR formulations of carbofuran have exhibited greater potential for effective 59
management of pests than the commercial formulation
thiram nanomicelles slow-releasing properties have been achieved due to encapsulation, and their applications can be optimized to achieve 56
disease control for the desired period
thiamethoxam nanomicelles more time is required for releasing 50% of the active ingredients in sandy loam soil than for commercial formulations 60
acephate nanocapsules nanoencapsulated acephate retained greater functional integrity over time and was more efficacious than commercial 207
formulations
Journal of Agricultural and Food Chemistry

2 PCAPEGPCA triblock imidacloprid nanocapsules dosage of pesticide and environmental risk significantly decreased due to nanoencapsulation of imidacloprid 49
copolymers
3 poly(-caprolactone) (PCL) AI aanospheres better stability of nanospheres was obtained in an aqueous suspension over 2 months 208
4 polyacrylate (PAL) emamectin nanoparticle photostability and insecticidal effects of the novel emamectin benzoate formulation increased and were better than those 209
benzoate conjugation of the commercial pesticide formulation
B. Natural Polymer/Polysaccharides

1465
1 chitosan-co-(D,L-lactide) imidacloprid nanomicelles sustained release of imidacloprid was achieved 46
2 alginate/chitosan paraquat nanoparticles release profile of the herbicide was altered as was its interaction with the soil, indicating this system could effectively 210
minimize the problems caused by paraquat
3 sodium alginate imidacloprid nanocapsules exhibited less cytotoxicity but retained better pest efficacy over plain imidacloprid 40
4 biocopolymers of methomyl nanocapsules insecticidal activity of methomyl-loaded nanocapsules against armyworm larvae was significantly superior to the original, 43
azidobenzaldehyde and even 100% over 7 days
carboxymethyl chitosan
C. Lipid-Based Nanomaterials
1 Compritol 888 (lipid) -cyhalothrin solid lipid nanoparticles reduced toxicity to aquatic fish (Brachydanio rerio) and daphnia (Daphnia magna) by factors of 10 and 63, respectively, 211
(SLNs) compared to the traditional emulsifiable concentrate
2 chitosan coated lipid entofenprox liposomes better pest control efficacy was observed for a longer period 93
3 chitosan-coated beeswax (solid deltamethrin SLNs chitosan-SLNs demonstrated ability to protect deltamethrin against photodegradation 212
lipid)
4 corn oil (liquid lipid) and beeswax deltamethrin nanostructured lipid higher payload, slower release rate, and higher photoprotection were obtained due to incorporation of corn oil compared 213, 214
(solid lipid) carriers to SLN
D. Porous Nanomaterials
1 silica tebuconazole porous hollow silica slower release of the active ingredient was noted in water under different conditions 24
nanospheres
2,4-D and picloram mesoporous silica slower release of the active ingredient was achieved up to 26 days for 2,4-D and up to 30 days for picloram 215
nanospheres
imidacloprid mesoporous silica release of imidacloprid from these nanoparticles was found to be controlled over 48 h 114
nanosparticles
metalaxyl mesoporous silica slower release of metalaxyl was exhibited from mesoporous silica nanospheres in soil than the free metalaxyl 116
nanospheres
Review

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 Table 3. continued
Sl nanoencapsulation
no. encapsulation material pesticide/biocide material/form improved features achieved due to nanoencapsulation refs
E. Clay and LDHs
1 bentonite, kaolinite, and fullers carbofuran nanocomposites adding clay particles in the formulations reduced the release of active ingredients 216
earth with polymer
2 montmorillonites and wheat gluten ethofumesate nanocomposites slow-releasing properties were achieved due to clay/pesticide interactions 217
F. Microemulsions
1 oil phase, surfactants, and water novaluron O/W microemulsions enhanced solubility was observed 196
2 oil phase, surfactants, and water permethrin microemulsion better pest control efficacy than commercial permethrin 218
G. Nanoemulsions
1 oil phase, surfactants, and water -cypermethrin O/W nanoemulsion sprayed solution of nanoemulsion formulation exhibited better stability than commercial microemulsion of - 192
cypermethrin
2 oil phase, surfactants, and water triazophos O/W nanoemulsion stability of triazophos improved and was protected from hydrolysis by being incorporated into the nanoemulsion system 187
3 oil phase, surfactants, and water glyphosate O/W nanoemulsion results of pot experiment indicated slightly better efficacy than the commercial formulation popularly known as 219
Roundup
H. Nanosuspensions
Journal of Agricultural and Food Chemistry

1 Eudragit S100 (polymer) AI nanosuspension enhanced penetration into the plant was observed; it was due to smaller particle size than the classical suspension 208
2. PAA-b-PBA, PVP and PVOH bifenthrin nanosuspension controlled and efficient release of bifenthrin was observed from polymeric stabilized suspension 220
3 microemulsion -cypermethrin nanosuspension particle size was increased, but no influence over composition was observed 197
Biocides
A. Synthetic Polymer/Polyesters
1 polyethylene glycol (PEG) garlic essential oil nanocapsules encapsulation materials reduced volatilization of essential oils and retained 80% pest control efficacy over 5 months 32

1466
azadirachtin-A nanomicelles in water, the rate of release of encapsulated azadirachtin-A from nanomicellar aggregates was reduced by increasing the 57
molecular weight of PEG, which controlled half-release time (t1/2) of 3.05 to 42.80 days
lansiumamide B nanocapsules in pot experiment, nanoencapsulated lansiumamide B showed higher nematicidal activity compared to only lansiumamide 34
B, where LC50 values of 2.1407 and 19.3608 mg L1, respectively, were observed after 24 h of treatment
B. Natural Polymer/Polysaccharides
1 amphiphilic chitosan derivatives rotenone nanomicelles solubility of rotenone increased (up to 26.0 mg mL1), which was about 13000 times greater than that of free rotenone in 64
water (about 0.002 mg mL1)
azadirachtin nanomicelles azadirachtin was protected by the carriers from rapid degradation and released over the course of 11 days into the 65
environment
2 chitosan and cashew gum Lippia sidoides oil nanogels slower and sustained release of Lippia sidoides oil was noted in in vitro release profiles, whereas more effective larvicidal 72
efficacies were obtained compared to the pure L. sidoides oil
3 gelator methyleugenol nanogels evaporation of pheromone significantly slowed and remained stable in open ambient conditions 74
(pheromone)
4 myristic acid and chitosan Carum copticum oil nanogels nanogels exhibited more fumigant toxicity than the free oil over a longer period of time to control store grain pest 73
C. Lipid-Based NPs
1 Compritol 888 ATO (lipid) Artemisia solid lipid nanoparticles physical stability was obtained as the solid lipid nanoparticles reduced the rapid evaporation of essential oils 110
arborescens L. (SLNs)
essential oil
D. Porous Nanomaterials
1 silica avermectin porous hollow silica release of avermectin can be controlled by adjusting pH and temperature; UV-shielding properties were improved when 120, 221
nanoparticles shell thickness was adjusted
(PHSNs)
validamycin PHSNs controlled-release formulations were prepared 122
Review

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Journal of Agricultural and Food Chemistry Review

refs

159

182

222
181

223
acaricidal activity demonstrated by neem oil microemulsion was effective against Sarcoptes scabie var. cuniculi larvae in

better stability of capcicin loaded nanoemulsion was obtained due to electrostatic interactions of the polymers
considered to be a green pesticide due to its controlled-release and nature compatibility properties

Figure 29. Releasing patterns of active ingredients from nano-

improved features achieved due to nanoencapsulation

encapsulation materials (adapted and modied from ref 76).

thiamethoxam60 from nanomicellar aggregates. The half-release

time (t1/2) of -cyuthrin varied from 5.09 to 7.9 days, and
POA ranged from 14 to 20.5 days for dierent formulations.58
In contrast, t1/2 of thiamethoxam and imidacloprid ranged from
3.56 to 6.07 days and from 2.32 to 9.31 days, respectively.55,60
In another investigation, Kumar et al.57 investigated the eects
larvicidal efficacy increased when droplet size decreased

of dierent polymers (commercial PEG, modied PEGs with

dierent molecular weights, and polyvinyl chloride (PVC)) on
superior larvicidal efficacy compared to bulk oil

the controlled release of encapsulated azadirachtin. Their study

concluded that t1/2 of encapsulated azadirachtin from modied
PEGs varied from 3.05 to 42.80 days, whereas the t1/2 values
from commercial PEG, PEG-1800, and PVC were 3.05, 21.36,
and 42.80 days, respectively.57 This nding indicated that not
F. Microemulsions
E. Clay and LDHs

G. Nanoemulsions

only the molecular weight of PEGs but also the types of

polymers aect the release of pesticides from encapsulation
materials. In this way, the application rate of pesticides can be
optimized to achieve insect control at the desired level and
period by adjusting the release rate of AIs, changing the types,
proportions, and molecular weights of the polymers. In all of
vitro

these investigations, sustained release of AIs was observed

where the AIs were released by the diusion process. The
releasing behavior through a diusion process from polymeric
nanohybrid of C-LDHs

device or carrier materials has been explained elsewhere.225

nanoencapsulation
material/form

4.1.2.2. Controlled Release of AIs from Lipid-Based

Nanoencapsulation Materials. Lipid-based nanoencapsulation
microemulsion

nanoemulsion
nanoemulsion

nanoemulsion

materials such as nanoliposomes are thermosensitive in nature

and can undergo a phase transition (Tc) upon heating at
temperature lower than their melting point (Tm). In fact, the
phospholipid ingredients of liposomes are responsible for such
properties.77 At this temperature, the lipid bilayer loses the
pesticide/biocide

ordered packing structure and the interfacial rheological

eucalyptus oil

properties of liposomes are dramatically changed. The uidity

cinnamate

neem oil

neem oil

of the bilayer increases, which makes them very susceptible to

capcicin

mechanical stresses, causing disintegration of lipid layers and

releasing the entrapped compounds.78 In this way the phase
transition temperature is very important for releasing the AIs
nonionic surfactant Tween 20 and

above a xed temperature. For example, lipids such as 1,2-

sodium alginate and chitosan
encapsulation material

dipalmitoyl-sn-glycero-3-phosphocholine have a phase transi-

tion temperature between 41 and 43 C, and the AIs trapped in
Tween 80 and SDBS

this lipid are released at this temperature.226 The phase

Tween 80 and water
Table 3. continued

transition temperature of phospholipids as well as lipid bilayers

can be changed by tuning or adjusting several parameters such
as polar headgroup, acyl chain length, degree of saturation of
water

the hydrocarbon chains, and nature and ionic strength of the

LDHs

suspension medium.77 Taylor et al.78 reported that Tc can be

lowered by decreasing the chain length and by unsaturation of
no.
Sl

1
2

the acyl chains as well as the presence of branched chains and

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Journal of Agricultural and Food Chemistry
strong head groups. Such thermosensitivity can also be
achieved by incorporating specic polymers into the bilayer
of nanoliposomes or coating them with polymers. In terms of
thermosensitivity, the water solubility of a polymer depends on
temperature and should have a critical temperature. Above this
temperature the polymer becomes water-insoluble and
destabilizes the liposome by interacting with the membrane,
resulting in AIs being released.227 Similarly, the release of AIs
from nanoliposomes stimulated by the structural properties of
pH-sensitive polymers remains at the vesicles outer layer.228
For instance, Cho et al.229 prepared a pH-sensitive polymer
liposome complex using unsaturated poly(methacrylic acid-co-
stearyl methacrylate), phosphatidylethanolamine, and oleic
acid, which destabilize the liposome in the acidic state and
release encapsulated active molecules. Therefore, a burst-
releasing pattern of the bioactive compounds is mostly
observed in nanoliposomes due to their thermosensitive and
pH-sensitive nature. Although this trait is suitable for drug
delivery to specic cells, it hinders their application in pesticide
delivery. To overcome this limitation, the liposomes are
generally coated with polymers to achieve sustained release of
AIs, where their release is aected by the molecular weight and
concentration of polymers being used. As an example, CRFs of
entofenprox were prepared as nanoliposomes where nano-
chitosan was used as a coating material.92,93 The released
amount of AIs was controlled by the molecular weight and
concentration of chitosan.93
In terms of SLNs, both burst and sustained releasing patterns
are observed. The releasing patterns depend on the entrapment
of active compounds in the nanoparticles. Fathi et al.76 noted
that burst release of active compounds occurs when the active
compounds are trapped at the outer shell of the solid lipid
nanoparticles, whereas sustained releasing patterns are observed
when the active compounds are trapped at the inner core of
SLNs or homogeneously distributed throughout the SLNs.
They also noted that if the active compounds are trapped at the
core of SLNs, the active compounds release is controlled by
the diusion process. On the other hand, their release is
controlled by the dissolution process when the active
compounds are homogeneously distributed in the SLNs.76
4.1.2.3. Controlled Release of AIs from Porous Silica
Nanomaterials. Porous inorganic nanoparticles such as PHSNs
have also been employed for preparing a CRF of pesticide while
the pesticides were loaded into the inner core of the porous
structure.120,122 The release of AIs from PHSNs can be
controlled by adjusting the pH of the medium and temperature.
Wen et al.120 reported that the release of avermectin increased
with raised pH of the medium and temperature. Similar results
were obtained for the pesticide validamycin.122 During
encapsulation of these pesticides with PHSNs, it emerged
that the release of AIs was very fast in the rst few minutes, but
the release rate became much slower after several hundred
minutes.120,122 Such release properties are very interesting in
terms of immediate pest control as well as the continuous
suppression of the pests.
The pesticides are loaded on dierent parts of the PHSNs
(external surface, pore channels, and in the wall of the inner
core), and the amount of pesticides absorbed at the external
surface dissolves quickly. On the other hand, a signicant
amount of pesticides remains inside the inner core, resulting in
pesticide residues. Qian et al.24 examined the release kinetics of
tebuconazole (used as a fungicide) from porous hollow silica
nanospheres and the factors related to loading ecacy and
1468
Review
controlled-release behaviors. They found that factors such as
pH, temperature, and size of the nanospheres signicantly
aected the release behaviors of tebuconazole from tebu-
PHSNs, and the release of free tebuconazole from tebu-PHSNs
occurred through diusion-controlled mechanism. Similarly,
mesoporous silica nanoparticles (MSNs) were eective carrier
materials for controlled release of AIs. The release prole of AIs
depends on the type of mesoporous structure and surface area
of particles. Popat et al.114 investigated the controlled release of
imidacloprid from various types of MSNs. They concluded that
the highest adsorption capacity of imidacloprid occurred in the
MSNs with a 3D open network structure and high surface area.
Release of imidacloprid from these nanoparticles was found to
be controlled over 48 h where, initially, the release was
controlled by the diusion process and later by the dissolution
process. Due to such a releasing prole and high water
solubility, 40% of the AI was released within the rst few
hours.114 When metalaxyl was loaded into MSNs, a delayed and
sustained release of metalaxyl was also observed.116
4.1.2.4. Controlled Release of AIs from Clays and LDHs.
Clays and LDHs can potentially serve as a matrix for
developing CRFs of agrochemicals.125 Generally, clays are
modied using dierent surfactants, and the ecacy of clays
depends on the concentrations and types of polymers or
surfactants used for modication along with their types.
Controlled release of nanoclays was engineered by surface
coating with dierent polymers, which played a signicant role
in the modication of electrostatic interaction between the
chemical load and clay particles.126 Choudhary et al.216
prepared controlled-release pesticide formulations of carbofur-
an using carboxymethyl cellulose (CMC) with clay such as
bentonite, kaolinite, and Fullers earth. In a comparison study
between commercial granules and CRFs of CMCclay, it was
found that the release kinetics of carbofuran in soil was faster
than that of CMCclay-based formulations. The half release
(t1/2) values were 4.79, 16.08, 17.07, and 21.32 days for
commercial granules, CMCkaolinite, CMCbentonite, and
CMCFullers earth, respectively, but the POA reached its
maximum for CMCbentonite (43.97 days).216 They also
investigated the ecacy of clay materials, preparing the
formulation with CMC and CMCclay separately, where the
t1/2 value and POA of CMC were less than those for CMC
clay-based formulations. These results indicated that slow
releasing properties are enhanced when clay materials are added
to the polymer matrix. Similar results were obtained by
Chevillard et al.,141 where the controlled release pesticide
formulations of Ethofumesate were prepared with wheat gluten
and clay particles, specically montmorillonites (MMT). They
reported that the release of Ethofumesate slowed for all wheat
gluten-based formulations compared to commercial products,
but the slow release eect increased in the presence of
hydrophobic MMTs. Temperature played a signicant role in
the release patterns because the activation energy of diusion
improved when the temperature increased.141
In agricultural applications, LDHs exhibit similar eects on
clay, and their structure oers more interesting features such as
accommodation and the controlled release of various active
anionic agro-substances, high buering capacity, high water
retention ability, and acid-neutralizing potential.125 Park et
al.159 prepared CRFs of cinnamate encapsulated with LDHs.
The release patterns of AIs were found to be diusion-
controlled as well as a simple ion exchange process. The initial
release of cinnamates was 40% within 1 h; after that, the release
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slowed, and >80% release into the solution was observed within
3 days. The release of AIs was rapid due to the ion exchange
process230,231 and, subsequently, a slow and steady release was
obtained due to the diusion process.159 Several medium
properties also inuence the release, such as pH, temperature,
buer conditions, or the presence of electrolytes.232
4.2. Enhanced Solubility. Poor solubility is one of the
major problems concerning pesticides, and it restricts their
ecient use. Such pesticides are available in the form of dust,
emulsiable concentrates (EC), and emulsions.194 Emulsiable
concentrates still occupy a major portion (28%) of the total
number of formulations listed in the pesticide manual published
in 2007.233 Due to their poor solubility in water, pesticides
suer more during spraying; very often, AIs in these
formulations accumulate at the bottom of a sprayer tank.
Larger droplet sizes of these AIs are mainly responsible for poor
stability after dilution. To maintain their stability and proper
dispersion, organic solvents (such as xylene, toluene) are used
in pesticide formulations, but this leads to increased cost and
creates dermal toxicity in handlers.233
Improving the properties of poorly water-soluble pesticides is
a foremost area of research. So far, remarkable progress has
been made to enhance poorly soluble drugs by producing a
nanosuspension drug delivery system.234 Solubility can be
enhanced through nanonization. The saturation solubility
increases with decreasing particle size according to the
OstwaldFreundlich eq (eq 3) (also known as the Gibbs
Thomson and Kelvin equation):
S(d ) V cumulative release of AIs from emulsion formulations was
= exp m
S0 RTd (3)
S(d) is the solubility (mol kg1 H2O) of crystals with inscribed
diameter d (m) at temperature T (K), molar volume Vm (m3
mol1), and surface free energy (surface tension) (mJ m2). R
is the gas constant (8314.5 mJ mol1 K), and S0 is the solubility
of the bulk material (d ).
With all other factors kept constant, solubility increases with
smaller particle size. However, for solubility S(d) to dier
signicantly from solubility S0 of the bulk material (i.e., the ratio
S(d)/S0 1), the exponential term needs to be much smaller
than 1. This occurs only with a particle size in the nanorange.
This aforementioned phenomenon is another demonstration
for the transformation of the physicochemical properties of
materials on the nanoscale. Similarly, other nanoencapsulated
pesticide formulations such as microemulsion and nano-
emulsion have also been prepared to avoid the disadvantages
of available commercial pesticides. Micro- or nanoemulsions
can also improve the pesticides solubility and bioavailability.6
Furthermore, it was suggested the nanosized aqueous
dispersion formulation enhanced the solubility of pesticides.
Nanosized aqueous dispersions or nanosuspensions eliminated
the need for organic solvents and provided a process for
stabilizing formulations of two or more immiscible pesticides.
The supercial solubility of poorly water-soluble pesticides can
be increased through encapsulation with additives such as
surfactants and polymers or by means of nanoparticulate
formation with changing solid structures.235 Lipid-based
nanoencapsulation materials can also be used to solubilize
water-insoluble lipophilic active compounds.76
4.3. Protection against Premature Degradation.
During their application conventional pesticides enter the
environment in several ways such as degradation, volatilization
1469
Review
or evaporation, and leaching.236 Yet a modern pesticide should
have the ability to survive in the spray environment.202 At
present, several pesticides are sensitive to UV light and have a
very short life; for example, avermectin (6 h)221 is volatile in
nature or tends to be leached down. To protect liable pesticides
from photodegradation, the microencapsulation technique was
introduced.237 The shell of the microcapsules is usually very
thick and compact, which inhibits the proper release of AIs
from capsules. Consequently, the nanoencapsulation technique
was introduced to solve the disadvantages of the micro-
encapsulation technique. Nanoencapsulation is such an eective
technology that it has the ability to protect pesticides from
premature degradation, maintaining their eective release.221
PHSNs were reported as acting like a shield that protected
the photosensitive pesticide avermectin as well as maintaining
its apposite release.169,221 Besides other factors (pH, temper-
ature), shell thickness of PHSNs signicantly aected the
loading eciency, UV-shielding property, and controlled
release of avermectin from PHSNs.169 UV-shielding eciency
rose and the release property slowed with increasing shell
thickness. PHSNs with a shell thickness of 15 nm and a pore
diameter of 45 nm increased the shelf life of avermectin up to
30 days.221 Generally, most biocides are essential oils extracted
from dierent plant parts, which are volatile in nature.
Nanoencapsulation materials were found to be eective for
reducing volatilization and releasing the active components in a
controlled way. Lai et al.110 investigated the ability of SLN to
prevent the rapid evaporation of the incorporated Artemisia
arborescens L. essential oil. They reported that at 35 C, the
double the formulations of SLN after 48 h. In another analysis,
polymeric nanocapsules of PEG loaded with garlic essential oil
reduced the volatility of active components and retained their
availability for a longer time.32
Clay materials can serve as an eective tool for protecting the
unstable pesticides against volatilization and photodegrada-
tion.125 In an earlier study, organoclay formulations exhibited
their potential to protect herbicides from photodegradation and
volatilization while maintaining their herbicidal activity.238 It
has been suggested that the reversible binding of the pesticide
on clay minerals is a feasible solution for reducing their leaching
into the environment via air and water.125 Leaching of AIs was
signicantly reduced with fungicides, namely, tebuconazole,
encapsulated in core/shell nanoparticles prepared from
amphiphilic copolymers of gelatin grafted with methyl
methacrylate.239
4.4. Increased Stability. Nanoencapsulation materials can
support AIs to achieve both physical and environmental
stability. The physical stability of AIs is required for long-
term storage and their successful application, whereas environ-
mental stability is required for eective pest control. The
nanoencapsulated pesticide formulations exhibited better
stability over time due to steric and electrostatic interaction
of dierent phases in the colloidal system. Conventional
pesticide formulations showed poor stability and disintegrated
during storage. The nanobased pesticide formulations have
exhibited their potential to remain stable for a longer storage
period. Wang et al.192 prepared nanoemulsion formulations of
-cypermethrin stabilized by polymeric surfactants. The
formulations exhibited good stability, even after 24 h of
dilution in comparison to commercial microemulsion, due to
the steric interaction between the polymeric inner surfaces with
pesticides. The electrostatic interaction between several
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polymers showed better eciency in stabilizing the nano-
emulsion formulation than the single polymers.222 Strom et
al.194 used milling technologies in the presence of grinding
media (polymer beads) and surface active agents to obtain
stable nanosuspensions of various fungicides and insecticides
with particle sizes of around 148314 nm.
The eects of dierent stabilizing polymers have been
investigated during nanosuspension formulation preparation of
the poorly water-soluble pesticide bifenthrin using a ash
nanoprecipitation process.220 It was reported that pesticide
formulations encapsulated with PAA-b-PBA, PVP, and PVOH
were most stable over time, having an average particle radius
distribution of 97171 nm, and the concentration and type of
stabilizers signicantly aected the size and stability of
formulations.220 On the other hand, although the average
particle radius distribution was 7080 nm with pluronic, PS-b-
PEO and PEG-b-PCL, macro-phase separation was observed
after 7 days.220 Although not focusing on agriculture, Anjali et
al.240 reported the nanoemulsion formulation of the articial
polymer-free nanopermethrin served as an eective larvicide
that was stabilized by plant-extracted natural surfactants.
Controlled-release properties and protection against pre-
mature degradation ultimately enhance the environmental
stability of AIs. For example, the stability of avermectin
increased from 6 h to 30 days through encapsulation with
PHSNs. The encapsulation materials permitted a controlled
release of AIs and protected them from UV light.221
Phytochemicals such as secondary metabolites and essential
oils have already shown their ecacy in pest control, but they
are nonpersistent in water and soil. Essential oils are usually
unstable in nature and evaporate as well as degrade rapidly in
the presence of air, light, moisture, and high temperature.
Nanoencapsulation of such essential oils has enhanced their
stability while maintaining their pest control ecacy for a long
period of time. To improve environmental stability, eective
maintenance, and bioavailability, lanssiumamide B was
encapsulated in the form of nanocapsules.34 The nanocapsule
suspensions were kept at 54 and 0 C and, after 14 days,
encapsulation eciency declined slightly at 54 C but did not
change at 0 C, indicating their good stability.34 Other studies
of nanoencapsulation discovered it was signicantly related to
increasing pesticides eectiveness. Boehm et al.208 investigated
the encapsulation ecacy of Eudragit S100 polymer. They
concluded that the nanosphere formulation prepared by
Eudragit S100 polymer was not eective in terms of controlled
release of AIs because the encapsulation rate was only 3.5%.
However, their penetration in the plant was enhanced due to
the particle size (135 nm) being smaller than the classical
suspension.208 In their review paper, Tadros et al.191 stated that
nanoemulsions enhance the wetting and spreading and
penetration ability of the droplets due to their low surface
tension of the whole system as well as low interfacial tension of
emulsion droplets. In another study, Song et al.187 observed
that the hydrolysis of organophosphorous insecticides such as
triazophos is pH-dependent and easily hydrolyzed in basic
solutions. To protect the insecticide from being hydrolyzed, a
nanoemulsion formulation was prepared where the eect of
surfactants was prominent in basic conditions to prevent the
hydrolysis compared to acidic or neutral pH.
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5. PEST CONTROL EFFICACY OF
NANOENCAPSULATED PESTICIDES
It is expected that the nanoencapsulated pesticides should have
better pest control ecacy over commercially available
pesticides, nonencapsulated pesticides, or microencapsulated
pesticides. Judging by the available literature, nanoencapsulated
pesticides have already exhibited better pest control ecacy
than commercially available pesticides or those without
encapsulated active compounds. Pest control ecacy refers to
dierent aspects based on the nano-guard properties of
nanoencapsulated materials. Nanoencapsulation materials
allow the release of active ingredients in a controlled way,
resulting in the retention of pest control ecacy over a longer
period than commercial formulations. Various CRFs have
already been prepared using dierent nanoencapsulation
materials, and their release behavior has been described in
the previous section. On the other hand, several investigations
have observed the pest control ecacies of those nano-
encapsulated CRFs.
For controlling stored-grain pests, repeated application of
pesticides or biocides is required due to their fast releasing
characters as well as shorter POA. Nanoencapsulated CRFs
were found to be an eective tool to control stored-grain pests.
Loha et al.206 evaluated the pest control ecacy of nano-
encapsulated CRFs of -cyuthrin on the mortality of
Callosobruchus maculatus. They developed CRFs by encapsulat-
ing -cyuthrin with PEG originated amphiphilic copolymers in
the form of nanomicelles. The bioecacy data of these CRFs
with commercial 025 SC indicated that on the rst day of
application the EC50 (eective concentration for 50% mortal-
ity) of commercial -cyuthrin (0.51 mg L1) was much lower
than the CFRs (97.24, 85.46, 59.89, and 37.32 mg L1 for
polymers having PEG-600, PEG-1000, PEG-1500, and PEG-
2000, respectively). After that, the EC50 of commercial -
cyuthrin increased rapidly. Interesting features were noted
among the dierent CRFs. The lowest EC50 of CRFs having
PEG-600 and PEG-1000 (1.89 and 1.03 mg L1, respectively)
were observed on the 7th day of application, whereas for CRFs
having PEG-1500 and PEG-2000 (2.20 and 1.1.58 mg L1,
respectively) on the 14th day of application. The EC50 values of
commercial -cyuthrin on the 7th and 14th days of
applications were 43.24 and 129.21 mg L1, respectively.206
Another study examined the release pattern of -cyuthrin
from these formulations in water.58 It emerged that the
releasing rate of commercial -cyuthrin was higher than the
CRFs and resulted in the lowest POA. Of the CRFs, the POA
increased with increasing carbon chain of PEG, that is, the
order of POA is PEG-2000 (20.5 days) > PEG-1500 (18.0 day)
> PEG-1000 (15.8 days) > PEG-600(14 days) > commercial
025 SC (1.4 days).58 However, the function of hydrophilic
segment of PEGs was not clearly stated. Basically, -cyuthrin
is not persistent because once it is in the water, it disappears
rapidly because it has poor water solubility and extremely high
adsorption anity to organic material. That is why commercial
-cyuthrin degrades rapidly in water and minimum POA was
observed. On the third day, EC50 values of CRFs having PEG-
600 and PEG-1000 were higher than the CRFs having PEG-
1500 and PEG-2000, which indicates longer polymeric chain
absorbed more -cyuthrin within the shell of micelles. This
caused faster release that was initially responsible for lower
EC50. On the other hand, a longer polymeric chain enhanced
shell thickness and reduced the diusion release rate, resulting
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in delayed EC50 as well as increased POA. These results suggest
that depending on the polymer matrix used, the application rate
of -cyuthrin can be optimized to achieve insect control at the
desired level and period, as the hydrophilic segment inuences
the active compounds release. Overall, the developed
formulations retained their ecacy for longer periods than
the commercial -cyuthrin. Similar results were also observed
during the bioecacy investigation of CRFs of carbofuran
against the root-knot nematode (Meloidogyne incognita)
infecting tomato plant (cv. PusaRuby).59 In both pot and
eld conditions, the developed formulations with PEG-600 and
PEG-900 showed better response at dierent concentrations
than commercial carbofuran in controlling the penetration as
well as further development of second-stage juveniles (J2s) of
M. incognita on tomato root system. In contrast, developed
formulations with PEG-900 exhibited better ecacy than the
formulation with PEG-600.59
In a study, Choudhary et al.216 evaluated the bioecacy
CRFs of carbofuran against M. incognita. The CRFs were
prepared by encapsulating carbofuran with commercially
available rosin and NaCMC. Release of carbofuran was faster
from commercial formulations than with new CR formulations.
In addition, the rate of release declined due to the introduction
of clay (bentonite, kaolinite, and Fullers earth) materials to the
biodegradable clay materials. The half-release (t1/2) values of
dierent CRFs along with commercial formulations ranged
between 4.79 and 25.11 days, and the POA of carbofuran
ranged from 15.10 to 43.97 days, where the lowest value was
observed in commercial formulations. The orders of release of
rate, t1/2 values, and POA of dierent formulations were
(release rate) commercial granule 3G > rosin-yellow >
CMC > CMCkaolinite > CMCbentonite > rosin-
black > CMCFullers earth;
(half-release (t1/2) values) commercial granule 3G <
rosin-yellow < CMC < CMCkaolinite < CMC
bentonite < CMCFullers earth < rosin-black;
(POA) commercial 3G < CMC < rosin-black < CMC
Fullers earth < CMCkaolinite < rosin-yellow < CMC
bentonite.
The mean EC50 of the commercial formulation at 7 days after
treatment (DAT) was the lowest compared to CRFs, but at 35
DAT the mean EC50 was quite high when compared to those of
CRFs. The CRFs performed better than commercial for-
mulations in preventing the penetration and multiplication of
nematodes. Bioassay studies revealed that the CRFs of
carbofuran are able to combat nematodes eectively for longer
periods than commercial formulations.216
The pest control ecacy of nano- and non-nano-
pyriuquinazon was investigated by Kang et al.241 on Myzus
persicae (green peach aphid). The nano-pyriuquinazon
pesticide formulations were prepared by encapsulating
pyriuquinazon with polymeric chitosan at dierent concen-
trations. It was found that the best lethal eciency of
pyriuquinazon appeared at 2 days post-treatment, whereas
the nano-pyriuquinazon was eective after 14 days of
treatment.241
In their eld study, Adak et al.205 investigated the bioecacy
of nanoencapsulated CRFs of imidacloprid against major pests
of soybean, namely, Melanagromyza sojae (stem y) and
Bemisia tabaci (white y). Amphiphilic polymers synthesized
from polyethylene glycol and aliphatic diacids were used to
encapsulate the imidacloprid as a micellar aggregation. The
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micellar size of synthesized polymers ranged from 127.5 to 354
nm, and the encapsulation eciency varied from 75.02 to
97.9%. The results of their study showed that the CRFs manage
insects better than commercial formulations at lower dose and
do not leave any terminal residues in crops and soil.205 In
another study, Yin et al.34 obtained a similar result during their
evaluation of nematicidal ecacy of nanocapsules loaded with
lansiumamide B (NCLB) against Bursaphelenehus xylophilus
and second-stage juveniles of M. incognita. After 24 h of
treatment, the lethal concentration required for 50% mortality
(LC50) values of NCLB were reported to be 2.1407 and
19.3608 mg L1 for B. xylophilus and M. incognita, respectively,
whereas LC50 values of lansiumamide B and other nematicide
ethoprophos were much higher than the NCLB.34
Yang et al.32 investigated the insecticidal activity of
nanocapsules of garlic essential oil against Tribolium castaneum
(adult red our beetle). At a similar concentration (640 mg
kg1), nanoencapsulated garlic essential oil showed better pest
control ecacy than free garlic essential oil.242 The pest control
ecacy of the encapsulated garlic essential oil remained >80%
after 5 months, whereas it was only 11% for free garlic essential
oil.32 In another study, the relative control ecacy of
nanocapsules loaded with natural pyrethrin and abermectin
pesticide was >80% after 45 days.242 Thus, nanoencapsulation
materials reduce the volatilization of natural compounds and
retain their pest control ecacy for a longer period of time.
In an earlier study, Casanova et al.243 evaluated the
bioactivity of nanoemulsion of nicotine against Drosophila
melanogaster by assessing the lethal time (LT50). Nicotine
carboxylate nanoemulsion was prepared using a series of fatty
acids (C10C18) and surfactant known as Tween 80. The oil-
in-water nanoemulsion showed a monomodal size distribution
with mean particle size of 100 nm. For the smallest fatty acid
emulsion used, capric acid (C10), the best encapsulation
eciency was observed, but it had the lowest bioactivity. These
results were explained in terms of the insecticide being less
bioavailable in its active form due to the increased stability of
the organic salt formed between the insecticide and the fatty
acid. It is necessary to consider the acidbase interaction
between nicotine and appropriate fatty acids when preparing an
eective nicotine insecticide emulsion.243 This experiment
highlights the necessity of developing dierent kinds of possible
assemblies between the active compounds and the matrix, and
extensively studying the interactions in nanoscale formulations,
where sometimes nontrivial outcomes might be unexpectedly
observed.
In vitro insecticidal activity of pyridalyl nanosuspension was
evaluated by Saini et al.198 to control the larva of Helicoverpa
armigera (tomato fruit and shoot borer) compared to technical
materials and commercial formulations. Compatibility of
pyridalyl with sodium alginate was conrmed, and a
formulation was obtained by optimizing various parameters.
Remarkable insecticidal activity was indicated by pyridalyl
nanosuspension. The pyridalyl nanosuspension was found
eective in controlling the pest comparatively at lower dose
than the technical materials and commercial formulations. The
LC50 value of pyridalyl nanosuspension was 40 g L1, whereas
LC50 values of the technical material and commercial product
were 90 and 250 g L1, respectively. Bioassay results obtained
using the leaf dip method showed that the nanoformulation was
2.26 times more eective against H. armigera as a stomach
poison than the technical product and 6.25 times more than
commercial formulations. With the topical method, the LC50
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values obtained were 80, 150, and 250 g L1 for the
nanoformulation, technical material, and commercial formula-
tions, respectively.198 These results suggested that nano-
suspension is a viable alternative to commercial formulations
because it is eco-friendly and introduces much less pesticide
into the environment.
The spinosad insecticide excites the insect nervous system,
and its eciency depended on particle size. When particle size
of the spinosad nanosuspension applied to spider mites was 404
nm, the LC50 was 15 mg L1, which further decreased to 11 mg
L1 for 372 nm, 7.6 mg L1 for 332 nm, and 4 mg L1 for 163
nm.194 Adak et al.55 also reported that high solubilization power
and low critical micelle concentration of PEG-originated
amphiphilic copolymers may increase the ecacy of
formulations.
The studies cited above stated that nanoencapsulation
technology provides better pest control ecacy to active
ingredients than commercial formulations. CRFs prepared
through encapsulating the active ingredients by nanomaterials
increase the POA, control the target pest for a longer period,
and reduce the doses of pesticides required for eective pest
control. Several factors such as particle size, shape, morphology,
and type of nanoencapsulation material as well as their
encapsulation capacity signicantly aect pest control eciency
of nanoencapsulated pesticides. However, several studies
concluded that although the nanoencapsulated pesticides
retained their pest control ecacy for longer, initially their
release capacity was very poor, which may be one of the major
problems with regard to controlling a pest immediately. To
overcome this issue, application of both nanoencapsulated and
nonencapsulated pesticides was recommended by Kah and
Hofman.21
Nonencapsulated pesticides should control the pest imme-
diately at a minimum concentration, whereas the nano-
encapsulated pesticides will sustain their pest control ecacy
for a longer time. As a result, frequent application of pesticides
will not be required to kill pests, and this will reduce the
amount of pesticides application in the environment. This will
also reduce the costs of pesticides and labor, which nally
benet farmers. However, more research is required in this eld
to develop such pesticides, which will be able to control the
pest immediately, as well as retain their ecacy over a longer
period. For example, Hwang et al.93 prepared CRFs of
etopfenprox as a liposome. They reported that the pest control
ecacy of etofenprox against Spodopter litura lasted longer
when they encapsulated this as a liposome rather than as a
commercial pesticide. They also reported that the initial pest
control ecacy of liposomes was similar to the commercial
pesticide (100% mortality was observed). However, after a
certain period (13 days), the commercial pesticide lost ecacy
while the liposome-containing pesticide retained pest control at
>50% ecacy.93
6. NANOENCAPSULATED PESTICIDES REDUCE
EXPOSURE TO HUMANS AND THEIR
ENVIRONMENTAL IMPACT
6.1. Ways of Human Exposure to Nanoencapsulated
Pesticides. Introducing nanoencapsulated pesticides in
agricultural practices may pose new risks as well as benets
to people and the environment.16 The impact of nano-
encapsulated pesticides is still unclear, as most studies have
investigated the controlled-release behavior or sought to
improve their properties against premature degradation. Only
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a few studies were found related to their pest control ecacy
and fate in the environment. Thus, evidence of human exposure
to nanoencapsulated pesticides was dicult to nd, and no
single study examined human exposure to nanoencapsulated
pesticides.244 It is expected that human exposure to nano-
encapsulated pesticides will follow the same path as commercial
pesticides. In their review paper, Damalas and Eleftherohor-
inos245 analyzed exposure, safety issues, and risk assessment
indicators of commercial pesticides. They stated that human
exposure to commercial pesticides generally occurs through
occupational exposure in the case of agricultural workers in
open elds and greenhouses, workers in the pesticide industry,
and exterminators of house pests.245 It is very clear that people
who mix, load, transport, and apply formulated pesticides are at
the risk of greatest exposure due to the nature of their work,
resulting in possible acute and dangerous intoxications.246
However, irrespective of whether the occupation involves the
use of pesticides, the presence of such chemicals in the
workplace constitutes potential and sustained occupational
exposure. In some situations, exposure to pesticides can occur
from accidental spills of chemicals, leakages, or faulty spraying
equipment, resulting in direct or indirect skin contact through
clothing contamination. Solid or powdery pesticides may
generate dust while pesticide-containing bags, cans, or bottles
are being opened and loaded into the application equipment,
resulting in exposure to the face and eyes, as well as respiratory
hazards. The exposure of workers increases when they do not
pay attention to the instructions on how to use the pesticides
and, particularly when they ignore basic safety guidelines on
how to use personal protective equipment and fundamental
sanitation practices, such as washing hands after pesticide
handling or before eating. Nevertheless, exposure of the general
population to pesticides occurs mainly through the food chain,
that is, eating food and drinking water contaminated with
pesticides. In addition, considerable exposure to pesticides can
occur when living close to a workplace that uses pesticides or
even when workers bring home contaminated articles.247,248 On
the basis of the types of human exposure to commercial
pesticides, it can be assumed that the major routes of human
exposure to nanoencapsulated pesticides are
direct and indirect contact with nanoencapsulated
pesticides such as dermal adsorption.
direct inhalation of nanoencapsulated pesticides or air
contaminated with nanoencapsulated pesticides; and
exposure through the food chain, that is, eating food and
drinking water contaminated with nanoencapsulated
pesticides.
6.2. Human Health Concerns Linked to Nanoencapsu-
lated Pesticides. Although the methods of human exposure
to nanoencapsulated pesticides are expected to be the same as
those for commercial pesticides, in terms of nanosize only, their
application is a major health issue. Nanoparticles are as small as
1
/5000 the width of a human hair. Such small particles are able to
pass through the skin of living organisms, especially when it has
been damaged. Mortensen et al.249 investigated the skin
penetration of quantum dot (QD) nanoparticles in a murine
model and the eect of ultraviolet rays. They reported that QD
nanoparticles worked their way between the corneocytes of the
stratum corneum and penetrated deep into the epidermis and
dermis of an in vivo model exhibiting UVR penetration
exacerbation. They also reported that UVR induces an outside-
in barrier defect, likely due to a loss of epidermal calcium
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Figure 30. Cross section of human skin showing the dierent layers and appendages (adapted and modied from ref 255).
gradient and resultant stratum corneum lipid disruption. Thus,
due to the accelerated epidermal proliferation and dier-
entiation UVR, skin repair response did not prevent QD
nanoparticles from breeching the skin barrier. It is very
important to note that QD nanoparticle penetration strongly
depends on the condition of the skin and the characteristics of
the QD nanoparticles. The penetration of QD nanoparticles
did not attain the drastic levels seen in some ex vivo
nanoparticle tissue studies, even with mechanical exing
associated with normal animal motion.249
Not only dermal adsorption but also exposure of such tiny
materials via inhalation or the oral route has drawn attention as
the particles can accumulate in the lymph system, the liver, the
nervous system, and in other areas of the body.250 Hillyer and
Albrecht251 investigated the gastrointestinal uptake of nano-
particles in mice. They discovered that a smaller particle size
was correlated with a higher uptake in the small intestine.
6.3. Do Nanoencapsulated Pesticides Reduce Human
and Living Beings Exposure to Pesticides? Generally,
several factors aect exposure during the handling and
application of pesticides, such as the types of pesticide
formulations, weather conditions, frequency and duration of
handling, and general hygiene behavior of workers during
pesticide use.245 Applying nanoencapsulation technology in
pesticide formulations is revolutionary and has potential in
agricultural practices in terms of employing pesticides safely.
Dierent organic solvents are utilized for the preparation of
commercial pesticide (nonencapsulated) formulations to make
them stable, whereas nanoencapsulated pesticides disperse
properly in aqueous media without any organic solvents.3 Thus,
nanoencapsulated pesticides allow the organic solvent-free safe
application of pesticides.
From the perspective of dermal exposure of nanoencapsu-
lated pesticides, Alvarez-Roman et al.252 reported that such
exposure to nanoparticles depends on the properties of
nanocarrier materials, especially their solubility and biodegrad-
ability. They also reported that lipophilic non-biodegradable
carrier materials enhanced penetration through the skin and
accumulated preferentially in the follicular opening.252 Another
investigation found that penetration of nanoparticles such as
QD nanoparticles depends strongly on the skins condition and
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the characteristics of the QD nanoparticles249 It was reported
that nanoparticles such as TiO2 and ZnO that are used in
commercial sunscreens exhibit limited penetration in layers
below the lower stratum corneum and that the skin penetration
characteristics can be altered by using surface coatings on the
nanoparticles to make them waterproof.249 Researchers at the
University of Bath found that even the smallest nanoparticles
cannot pass through the skin barrier.253 A study by Campbell et
al.254 employed laser scanning confocal microscopy to observe
whether uorescently tagged polystyrene beads in the scale of
20200 nm were absorbed into the skin. They reported that
the minimal uptake was independent of contact time (up to 16
h) and nanoparticle size being tested. The nanoparticles could
not penetrate beyond the most supercial layers, corresponding
to a depth of 23 m, of the stratum corneum (the outermost,
1520 m skin layers, see Figure 30). Therefore, the
nanoparticles failed to reach the viable cells of the epidermis
or beyond.254
Inhalation exposure to pesticides is very sensitive as the
pesticides are readily absorbed by the human body, especially
the lungs. So far, various controlled-release pesticide
formulations have been prepared by encapsulation using
nanomaterials. Such nanomaterials (e.g., biodegradable poly-
mers) have also been investigated for the controlled release of
drug delivery. Due to their slow release properties,
encapsulation materials will release the pesticide in a controlled
way into the human body, which will reduce health risks
compared to nonencapsulated pesticides. The frequency and
duration of pesticide handling, on both seasonal and lifetime
bases, aect exposure. For instance, the exposure of an
individual farmer who applies a pesticide once a year is lower
than that of a commercial applicator who normally applies a
pesticide on many consecutive days or weeks in a season.246
General hygiene behavior of workers during pesticide use can
also have a substantial impact on exposure.256 The proper use
and maintenance of protective clothing are considered
important practices associated with reduced chemical expo-
sures. Furthermore, workers who avoid mixing and spraying
during windy conditions can reduce their exposure to
pesticides.
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Weather conditions at the time of application, such as air,
temperature, and humidity, may aect the chemical volatility of
the product, the perspiration rate of the human body, and the
use of personal protective equipment.246,257 Wind considerably
increases spray drift and resultant exposure to the applicator.
The amount of pesticide that is lost from the target area and the
distance that the pesticide moves will increase as wind velocity
increases; therefore, greater wind speed will generally cause
more drift. In addition, low relative humidity and high
temperature will cause more rapid evaporation of spray
droplets between the spray nozzle and the target than high
relative humidity and low temperature. In contrast to
commercial pesticides, nanoencapsulated pesticides reduce
exposure in such weather conditions by reducing volatilization
and increasing stiness, permeability, thermal stability, and
solubility.17
It is notable that the food chain is one of the major ways
through which humans can be exposed to nanoencapsulated
pesticides, especially non-biodegradable nanoencapsulation
materials. For example, metals/metalloids such as arsenic are
accumulated in the human body via the food chain and potable
water.258,259 In some investigations, the bioavailability of
inorganic nanoparticles was noted, particularly their ability to
accumulate in the human body via the food chain. To ensure
the good quality of food reaching consumers, nanoencapsulated
pesticides should be designed in such a way that they remain
free from residual eects. In a eld test with soybean, Adak et
al.205 evaluated the terminal residues of PEG-coated nano-
imidacloprid formulations utilized for seed treatment. They
reported that the accumulation of the pesticide on the soybean
seeds and soil at harvest was below the detection level of the
instrument.205 In an earlier study, similar investigations were
conducted by Guan et al.260 using chitosan-coated nano-
imidacloprid formulations on soybean leaves and soil. Their
results showed that the nal residues of imidacloprid in both
leaves and soil were 10 times lower than the permitted
maximum residue level of imidacloprid established by the
FAO/WHO.260 None of these studies investigated the fate or
residual eect of encapsulated materials in the plant or soil.
Transportation of nanoencapsulated pesticides and their release
behaviors from nanoencapsulated materials are very important
for identifying their probable fate and accessibility in the human
body via the food chain.
6.4. Environmental Impacts of Nanoencapsulated
Pesticides. Conventional pesticide formulations suer from
multigate problems due to their widespread, repeated, and
random application, which cause major impacts in the
environment. Therefore, a precise pest management system is
required to reduce the toxicity of pesticide application and
minimize any environmental hazard. The damage done by
available pesticides has necessitated the search for new pesticide
alternatives to reduce their usage. Therefore, technological
development is always a burning issue in the pesticide industry.
Of the latest technologies, encapsulation of pesticides or
pesticidal active ingredients with nanomaterials was found to be
the most eective. Nanoencapsulation technology has the
advantages of safer handling and more ecient use of pesticides
with less exposure to the environment, guaranteeing eco-
protection. They facilitate the eco-protection system to
pesticides by, rst, reducing the amount required for eective
pest control and, second, enhancing their sensitivity to target
and nontarget organisms.
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6.4.1. Reducing the Amount of Pesticide Use and
Residues. Nanoencapsulated pesticides showed better environ-
mental stability, controlled release, targeted activity, and
physical stability than other formulations. Various nano-
encapsulated formulations such as nanoemulsions also have
the capacity to increase the solubility and permeability of
pesticides.192 Nanoencapsulation materials can potentially
protect the AIs from immature degradation such as
volatilization, photolysis, and rapid evaporation. Some
pesticides are highly mobile in nature and are lost through
leaching and drainage, which eventually causes water pollution.
Nanoencapsulation materials minimize such losses by releasing
AIs in a controlled way. Slow-releasing properties as well as
encapsulation of AIs with hydrophobic nanomaterials can also
be eective tools to prevent any losses from drainage or runo.
The dispersion of hydrophobic pesticides in aqueous media can
be enhanced by nanoencapsulation, allowing a controlled
release of active compounds, which reduces the problems
associated with drifting and leaching. Such protection
mechanisms reduce the exposure of pesticides to the environ-
ment and retain their activity for a longer period of time.
Ultimately, the POA of AIs increases and enables them to
combat pests for longer periods by supplying the AI in a
controlled way at the optimum level. As a result, the
requirement for repeated and indiscriminate applications of
pesticides is reduced.58 Nanoencapsulated pesticides have also
exhibited better pest control ecacy at lower dose compared to
commercial formulations. A nanoencapsulated pesticide pos-
sesses higher surface area and, depending on the particle size,
the pesticide doses can be reduced.194 The biological activity of
AIs can also be reduced by soil sorption. As a result, signicant
amounts of pesticide remain as residues in the soil, but the
residue amount increases with continuous application of
pesticides. The level of residual toxicity is inuenced by their
shelf-lives, chemical stability, and bioavailability to the plant and
living beings. However, the development of new pesticide
formulations obtained from encapsulation with nanomaterials is
the possible solution to minimize the residual toxicity.
6.4.2. Less Toxicity to Nontarget Organisms. The non-
selective nature and residual availability of pesticides are major
concerns about pesticide formulations. With such properties
they are very toxic to nontarget organisms.261 It is expected that
nanoencapsulation technology will design a pesticide formula-
tion in a way that is safe for nontarget organisms, including
handlers, and will be toxic only to target pests. Nano-
encapsulation materials provide better interaction and a
modied mode of action at a desired target site of the plant
or pest due to its tunable controlled-release system and larger
surface area.262 As a part of smart delivery systems, nano-
encapsulation materials support pesticide active compounds in
being more selective without hindering access of the bioactive
compounds to the target pathogen.263 Pradhan et al.207
investigated the biosafety of PEG-encapsulated acephate on a
murine model and in vitro cytotoxicity in a human broblast
cell line. They did not nd any kind of abnormality, which was
indicated on the basis of parameters of acute oral toxicity and in
vitro cytotoxicity. In the case of pest control ecacy,
nanoencapsulated acephate acted excellently against a broad
spectrum of agriculturally harmful pests, both in vitro and in
vivo.207 In another analysis, pyrethroid insecticides such as -
cyhalothrin are known to possess high and unwanted toxicity
that aects aquatic organisms. Nanoencapsulation technology
proved to be eective in reducing such toxicity while retaining
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Table 4. Some Promising Botanical Pesticides and Their Mode of Action (Reproduced with Permission from References 265
(Copyright 2006 Annual Reviews), 266, 267 (Copyright 2000 Wiley), and 268 (Copyright 2014 Elsevier))

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insecticidal activity.211 Kumar et al.40 prepared a nano-
encapsulated formulation of imidacloprid coated with sodium
alginate. In their study, they found that nanoencapsulated
pesticide formulation showed less cytotoxicity while retaining
better pest ecacy over plain imidacloprid. Recently, improved
herbicide formulations were developed where the active
compounds were encapsulated with polymeric nanocap-
sules.38,261 Such a pesticide formulation performed better in
controlling the target species, whereas their genotoxicity tests
demonstrated less toxicity than the free herbicides.38,261 They
also reported that nanoencapsulation materials can modify the
properties of pesticidal compounds and reduce toxicity to
nontarget organisms.23 Therefore, nanoencapsulated pesticides
are biosafe and more eective compared to their commercial
counterparts with reported toxicity. Nanoencapsulation tech-
nology has great potential, but more investigation is required to
make pesticides more eco-friendly.
6.5. Nanoencapsulated Green Pesticides as a Safe
Application of Pesticides. The utilization of plant derivatives
is not a novel phenomenon for controlling agricultural pests.
The practice of using plant derivatives as pesticides began in
ancient times.264,265 Plant derivatives used for pest management
are considered to be attractive alternatives to synthetic chemical
pesticides because they pose little threat to the environment
and to peoples health. For example, azadirachtin is deemed
nontoxic to mammals, sh, and pollinators; the oral acute LD50
to rat is >5000 mg kg1, whereas its half-life is approximately 20
h.265 This explains why plant derivatives such as essential oils,
extracts, and isolated active compounds (biochemicals) having
pest control ecacy can be termed green pesticides or botanical
pesticides. However, some botanical pesticides have been
deemed toxic to humans, and subsequently their utilization has
been drastically reduced. For instance, nicotine, an alkaloid
obtained from leaf extracts of Nicotiana tabacum, is a well-
known insecticide, but its utilization has declined due to
extreme toxicity (acute oral LD50 to rat is 50 mg kg1) and
rapid dermal absorption in humans.266 Some promising
botanical pesticides and their modes of action are listed in
Table 4. Such pesticides constitute a major aspect of
biopesticides.265 Although such types of plant products are
considered safe for humans, generally, they are either unstable
or suer from premature degradation, for instance, high
volatility, thermal decomposition, etc.268 Because of such
properties, until now, their application is not up to the level
of commercial synthetic pesticides. Considering the benets of
botanical pesticides to humans and the environment, new
formulations with improved features in potency and stability
constitute a major research area in the pest management
industry.
The utilization of nanotechnology and especially the
widespread application of nanoencapsulation materials in a
drug delivery system have drawn attention to the selection of
safe materials for enhancing botanical pesticide formulations.
Recently, de Oliveira et al.268 reviewed an application of
nanotechnology for encapsulating botanical insecticides. They
noted that, except for a few botanical active compounds, their
utilization is limited to entomological concerns. Biochemicals
derived from other types of biopesticides can also be used for
strengthening the safe application of pesticides. In their review
paper, Copping and Menn267 mentioned other sources of
biopesticides such as micro-organism- and insect-derived
compounds.
1476
Review
So far, a number of investigations have commented on the
improved features of nanoencapsulated biopesticides (Table 3).
More importantly, the development of less harmful plant
protection products through nanoencapsulation was the focus
of most research. The types of nanoencapsulation materials
used were similar to those employed for drug delivery in
humans. Considering the environmental risk factors, the
nanoencapsulation materials that originated from biodegradable
polymers were quite promising in the formulation of less
harmful biopesticides. In recent years, biologically originated
biodegradable materials (beeswax, corn oil, lecithin, cashew
gum, etc.) were also used to prepare less harmful biopesticides
by encapsulating bioactive compounds, forming various nano-
materials.72,212,213 On the other hand, nanoencapsulation
materials such as amorphous silica nanoparticles were declared
safe for humans by the World Health Organization (WHO)
and U.S. Department of Agriculture,269 whereas nanoclays
already exist in the earth. It is expected that the wide ranges of
nanoencapsulation materials and encapsulation approaches are
able to simplify the synthesis of nanoencapsulated biopesticides.
The widespread application of dangerous biopesticides can be
overcome through nanoencapsulation, which may begin a new
era in which pesticides required for eective pest control in
agriculture are environmentally safe.
7. SUMMARY AND FUTURE TRENDS
The indiscriminate usage of agrochemicals, especially pesticides,
has drawn scholarly attention as they pollute the environment
and pose a danger to living beings. Nanotechnology is a recent
approach that is becoming increasingly important for delivering
pesticides and their safe application. Of all the various types of
nanotechnology related to pesticide delivery, this review
analyzed and presented the importance, ecacy, and trends
inherent in the nanoencapsulation technique. Dierent nano-
encapsulation materials have already shown their potential,
promising results and applications by encapsulating the
available pesticides and biocides. Among them, polymer,
porous silica, clay, and LDH-based nanomaterials were found
to be very important. Further studies are required to
understand the compatibility between the pesticides and
encapsulation materials as well as the encapsulation mechanism
of pesticide formulations. Of the wide potential applications of
nanoencapsulation techniques for pesticide delivery, developing
a slow-releasing property with enhanced solubility, perme-
ability, and stability is the main focus of current research. These
properties will be achieved through either protection of the
encapsulated active ingredients from premature degradation or
increasing their pest control ecacy for a longer period.
The controlled-release properties of nanoencapsulation
materials to release the AIs to the target area using autosensing
power need further investigation. Although complete features
(e.g., synthesis, ecacy, and their fate) related to these
nanomaterials are rarely found and promising nanoencapsu-
lated pesticides are at a very early stage of development, it is
expected that this technology will reduce, rst, the dosage of
pesticides needed for crop protection and, second, human
exposure to pesticides. A major contribution that is expected to
emerge from the auspicious results of green pesticides is the
application of nanoparticles to encapsulate and stabilize
bioproducts, which will reduce environmental hazards.
However, more studies will be required to establish common
synthesis procedures for a particular group of pesticides and to
assess the fate of nanoencapsulation materials. The main
DOI: 10.1021/acs.jafc.5b05214
J. Agric. Food Chem. 2016, 64, 14471483
Journal of Agricultural and Food Chemistry
challenges associated with nanoencapsulated pesticides are
whether they will be able to compete with existing formulations
in terms of both cost and performance or otherwise.
AUTHOR INFORMATION
Corresponding Author
*(R.N.) Phone: +61 2 4913 8705. E-mail: ravi.naidu@crccare.
com.
Funding
Md.N. is grateful to the University of Newcastle for the
University of Newcastle Postgraduate Research Scholarship
(UNIPRS) and to the Cooperative Research Centre for
Contamination Assessment and Remediation of the Environ-
ment (CRC-CARE) for scholarship funding. We acknowledge
the University of South Australia for the logistic and fellowship
supports to Md.N.
Notes
The authors declare no competing nancial interest.
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