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Biocompatible, photolumincesnt , partially oxidized porous

silicon nanostructures for slow and controlled delivery of


pharmaceutical payloads
Gopikrishna.j ,NMS 08014

1. Introduction
Silicon is the heart material of a number of electronic and electrical
gadgets which dominates our lives, such as computers iPhones etc. its
incomparable electrical properties had made it to be called as the “steel of
21st century”1

By demonstration of efficient optical properties of porous silicon by


Prof. Canham2 in 1990, novel application of this sort of silicon in
optoelectronics, optics and biophotonics had came into scene.

Again Prof. Canham in 1995 reported the behavior of pSi in a


simulated biological fluid (SBF), in contrast with the expected toxicity pSi
shown a high degree of biocompatibility. This alteration in the toxicity from
the bulk silicon is because of the rapid oxidation of pSi on to silicic acid,
which is a normal constituent of the body. More over this biodegradability
was directly related to the pore size of the pSi films3

There was an active debate about the origin and nature of the
luminescence from pSi particles. Some publications relate the light emission
to Si-O defects in the lattice surface 4, while others argue that the
luminescence is because of quantum confinement effect. The dispute is
almost resolved by a recent paper on Nature Materials, which demonstrated
both mechanisms on a single pSi lattice.5
Depending upon the pore size pSi is classified on to three types, i.e.
microporous, mesoporous and macroporous.6 Adjustable porosity,
biocompatibility, and optical properties are made porous silicon particles an
attractable candidate for biological applications like drug delivery and
imaging.

2. Synthesis of porous silicon nanostructures

Various methods had been reported in literature for the synthesis of


porous silicon nanostructures. The electrochemical etching of single
crystalline silicon wafers in the presence of hydrofluoric acid as electrolyte
solution is the most hailed one by researchers for its reproducibility,
simplicity and controllability.6

A simple anodization setup is only needed for the reaction, with


having positively biased single crystalline silicon wafer and a platinum (or
any other HF resistant conductor) as counter electrode. Ethanolic solution of
aqueous HF is used as electrolyte. Varying the parameters like current
density, type and concentration of the dopent, crystal orientation of the
wafer, and the electrolyte concentration can easily control the pore size7.
Porous silicon formed this way will be hydrogen terminated, having >99%
surface atoms capped with 1-3 atoms of hydrogen to satisfy their
tetravalancy7,8. Only one side of the Si wafer is exposed to the electrolyte
while other side is protected by an ohmic contact6.
Fig I. Schematic of Etch cell used, electro chemical reactions are shown 6.

Although the exact chemistry of the porous Si formation is not well


understood, the anodic reaction can be described as,

Si + 6HF ⇒ H2 SiF6 + H2 + 2H+ + 2e- 8

HF that is normally noncreative to SI-H terminated wafer is made to


be reactive by the supply of holes. The positive bias alleviates the surface Si-
H bonds and lead way to the formation of Si-F bonds. Pore formation occurs
as the Si atoms are removed from the surface in the form of SiF6. The
probability of the hole to accumulate on tip of the pore is large when
compared with that of the pore walls of pre existing pore, hence the reaction
kinetics is fast at the pore tips leading to the propagation of the pores
inwards.9,10
FigII.i. Mechanism of pore formation, the yellow arrow indicates the
etching direction.10

Jin-Ho Park4 et al recently reported a procedure for the preparation of


luminescent porous silicon nanoparticle from (100) oriented P-type doped
single crystalline silicon wafer by electro etching with 200mA/cm2 current in
3:1 (v/v) electrolyte of 48% aqueous HF in ethanol. The freestanding film of
porous silicon were then removed by a current pulse of 4mA/cm2 for 250 s
followed by ultrasonication overnight in DI water and filtration to prepare
nanoparticles. The formed particles were Si-O-Si terminated, ultrasonication
can be done in ethanol instead of DI to avoid oxidation.
Drying is an important part of the synthesis; spontaneous drying can
lead to cracking of the films hence drying under nitrogen flow after repeated
washing with ethanol is recommended.11

As-anodized silicon nanoparticles will be hydrophobic in nature


because of the hydrogen terminated surface, these particles are not
acceptable for in vivo application as they got a higher chance of recognition
by the compliment system leading to their elimination from the host4.
Surface modification of silicon naopartilces with hydrophilic entities or
surface fictionalization can be an attractive alternative.

3. Surface fictionalization.
The surface of as –anodized silicon is hydrogen terminated, (Si-Hx:
x= 1,2,3). The most frequently observed surface impurity is oxygen forming
Si-O-Si bonds rarely carbon is also seen. These impurities are not
accumulated as result of etching process but during the storage of as-
anodized samples for a long time, termed as ageing. Hence not only for any
biological applications but also to ensure stability surface fictionalization is
required7.

There are three methods explained extensively in literature, namely 1)


oxidation of porous silicon surfaces, 2) hydrosilylation by forming Si-C
covalent bonds and 3) thermal deposition of carbon.6

Among the mentioned methods hydrosilylation will be the most


preferred one for this study because it is reported to ensure biocompatibility
to the pSi films6, while oxidation and carbon deposition ensures rapid
biodegradability. For a slow and controlled drug release application
hydrosilylation like PEGlation can be employed.12,13
Fig III. various surface modifications by hydrosilylation13.
Jullian Buriack12 and team from Purdue University USA had reported
three most suitable methods for the surface modification of pSi using
hydrosilylation. Which includes Lewis acid mediated reactions (LAM),
Light induced reactions (LM) and cathode electro grafting (CEG). LM is
difficult to control, while ECG requires sophisticated experiment set up for
the reaction to carry out. On the other way LAM modification can be done in
room temperature in the presence of a Lewis acid like EtAlCl2 under
nitrogen filled environment in a glow box. The same team in 1999 reported
modification of pSi surfaces with alkynes and alkenes using LAM reactions.
Such modified samples were stable even on boiling at PH 12 for 30 minutes.

Naïve surface is H terminated, hydrosilylation in the presence of a Lewis acid as


EtAlCl2 produces alkyl and alkenyl terminated structures12
But the problem associated with hydrosilylation will be the quenching
of luminescence. This quenching effect is depended upon both the length
and complicity of the modifying agent, and also the degree of
hydrosilylation14. The least quenching of 28% was observed in the case of
1- dacane, which is a linear, simple molecule of 10 carbon units.7

Recently L T Canham15 etal reported a method for the partial


hydrosilylation- partial oxidation of pSi nanostructures. In this method a
limited amount of Si-Hx bonds remain even after modification, this can
undergo oxidation in a media with traces of water in it. The Si-O bond
formed by oxidation can induce luminescence while surface modification
will ensure stability.

Fine-tuning such a balance between the stability and luminescence


should be the focus of our current research such that porous silicon based
nanoparticle with luminescent properties, which also can be used for
controlled delivery of pharmaceutical payloads to target cells, could be
developed.

All the chemistry available on the literature is pertaining to the silicon


nano films, surface hydrosilylation of electrochemically etched porous
silicon nanoparticles had not reported. We can expect that the mechanism of
surface modification of silicon nano films will hold good for silicon
nanoparticle as well, but a great deal of optimization is required. Since the
modified surface will enhance the drug attachment, its good to perform the
drug loading step after hydrosilylation. But there is a possibility that the
modifiers will block the pores of silicon, if the partial modification is done
this hindering can be reduced.

4. Loading and controlled release of drugs with porous Si

Attachment of payloads to the carrier can be done in any of the


following three methods. 1) Covalent attachment of drugs- the reaction
kinetics and efficiency will be good but the release of drug from the carrier
will be a problem, moreover newly formed covalent bond may alter the
chemical property of the drug. 2) Trapping by oxidation- upon oxidation the
pore diameter of the pSi will reduce, thus trapping the payload inside, since
oxidation is not desirable in our case this method is not recommended,
nevertheless this reaction will we much efficient in the case of nano films
than naoparticles. 3) Drug loading by physical adsorption- adsorption may
be mere electrostatic, hydrophilic or hydrogen bonding. Changing the
conditions can easily reverse these attractions6. Moreover there will not be
any chemical modification of the drug. These properties make this mode of
attachment most attracting for the current research. Adsorption will depend
more upon the type of drug and the kind of surface modification, hence this
part requires further reading.
The delivery of small molecule inhibitors to alter the de novo
properties of canserous cell lines by nanoparticles is not discussed in
literature. Small molecule inhibitor for AML cell line could be a novel and
applicable payload for the pSi delivery vehicle in discussion.
Analysis
The degree of porosity and pore diameter can be calculated by using
scanning electron microscopy, the relationship between current density,
electrolyte concentration and etching time to the porosity have to be derived
from repeated measurements. Particle size, zeta potential and stabity with
out surface modification can be detected by DLS readings, to be reapeted
after hydrosilylation to understand the effect of modification. Luminescence
and other optical properties can be detected using spectrophotometer and
fluorimetry, there also one can expect a relation between optical properties
and fore mentioned etching parameters. Surface hydrogen passivation,
hydrosilylation and partial oxidation can be demonstrated using FTIR by
observing Si-Hx, Si-C and Si-O-Si bonds respectively. The intensities of the
peaks correspond to the number of bonds present, and hence by comparing
the intensities partial oxidation – partial hydrosilylation can be
demonstrated.
Fluorescent imaging of cell lines of choice can be done after
understanding the optical properties. Drug loading and release studies are
done conventionally by comparing the OD value of both bound and free
payload. Toxicity and in vitro biocompatibility studies have to done with
chosen cell line by using techniques such as MTT assay, FACS, cytogenetic
analysis etc. in vivo biocompatibility can be assessed by in vivo imaging
system after conjugating the particle with a near infrared emitting dye,
followed by biopsy.
In conclusion the basic intention of the current research is to develop a
porous silicon based biocompatible, photo luminescent, partially oxidised
nanoparticle for the slow and controlled delivery of a therapeutic payload to
the target cells.
References
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