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Preparation of cationic lipid layered PLGA


hybrid nanoparticles for gene delivery
ARTICLE in JOURNAL OF CONTROLLED RELEASE AUGUST 2015
Impact Factor: 7.71 DOI: 10.1016/j.jconrel.2015.05.154

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5 AUTHORS, INCLUDING:
Yoshie Arai
CHA University
7 PUBLICATIONS 5 CITATIONS
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Available from: R. Jagathesh Chandra Bose


Retrieved on: 05 January 2016

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Abstracts / Journal of Controlled Release 213 (2015) e8e152

following reasons: (1) the incorporation of nonionic PVP chains


increased the number of non-ionic groups in the polymeric network.
Thus, the synergistic effect of CO (N), CHO and COO groups is
superior to either of the single groups; moreover, PVP is an excellent
dispersant, which enhances dispersion of the reactants and improves
network structure of the hydrogels during reaction. This improved
polymer network is helpful for the uptake and release of DS. As a
result, a higher swelling ratio, encapsulation efciency and cumulative release are observed. (2) When the PVP content is higher than
10 wt.%, the excessive PVP may generate strong hydrogen bonding
interaction with COOH and CHO groups and tangle with the
grafted polymeric chains to form a physical crosslinking, which may
produce more crosslinking points and minimize the network space
for DS, and then stop DS from entering or coming out of the network.

implanted. Blood test and X-ray were performed on 8 and 12 weeks


(Scheme 1), and rat was sacriced for pathological and real-time
polymerase chain reaction analyses. All results demonstrated that the
above composite platform displayed bright prospects for application in
osteomyelitis and bone defect.

Keywords: carboxymethyl cellulose, polyvinylpyrrolidone, multicomponent semi-IPN polymer hydrogel bead, pH-responsive,
controlled release
References
[1] M. Shen, Y.Z. Huang, L.M. Han, J. Qin, X.L. Fang, J.X. Wang, V.C.
Yang, Multifunctional drug delivery system for targeting tumor
and its acidic microenvironment, J. Control. Release 161 (2012)
884892.
[2] W.B. Wang, Q. Wang, A.Q. Wang, pH-Responsive carboxymethylcellulose-g-poly(sodium acrylate) /polyvinylpyrrolidone
semi-IPN hydrogels with enhanced responsive and swelling
properties, Macromol. Res. 19 (2011) 5765.
doi:10.1016/j.jconrel.2015.05.152

Hydroxyapatite and vancomycin composited electrospun


polylactide mat for osteomyelitis and bone defect treatment
Qing Hana,b, Jianxun Dingb,*, Yuhao Zhenga, Xiuli Zhuangb,
Xuesi Chenb, Jincheng Wanga,*
a
Department of Orthopedics, Second Hospital of Jilin University,
Changchun 130041, China
b
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied
Chemistry, Chinese Academy of Sciences, Changchun 130022, China
Corresponding authors.
E-mail addresses: jxding@ciac.ac.cn (J. Ding),
jinchengwang@hotmail.com (J. Wang).
More and more accidents happen with the development of highspeed trafc, which cause a lot of traumas and fractures. There are
considerable numbers of cases which cannot be debrided thoroughly
due to the limited time in emergency rescue and complex structure
of bone. Acute infection and bone defects thus form and interact with
each other, nally leading to chronic and stubborn osteomyelitis and
larger bone defects [1].
In this work, a novel electrospun mat was established from
polylactide (PLA), hydroxyapatite-graft-polylactide (HA-g-PLA) and
vancomycin (Van) to treat osteomyelitis and bone defect. HA in the
electrospun mat can induce bone regeneration, while Van is the most
commonly used antibiotic for the treatment of osteomyelitis along
with bone cement. Both the quantitative tests in liquid medium and
that on solid matrix revealed superior antimicrobial effect of the
electrospun mat on Gram-positive bacterium (i.e., Staphylococcus
aureus) and Gram-negative one (i.e., Escherichia coli) [2]. On this
basis, an osteomyelitis and bone defect model was established by
making a 6 mm 2 mm defect on the proximal end of femur in male
Sprague-Dawley (SD) rat by injecting 104 CFU S. aureus into the femur.
1 week later, debridement was performed and the electrospun mat was

Scheme 1. Schematic process of electrospinning and treatment of osteomyelitis and


bone defect of rat.

Keywords: antimicrobial, electrospun mat, hydroxyapatite, vancomycin,


tissue engineering
Acknowledgments
This work was nancially supported by the National Natural
Science Foundation of China (81171681, 51303174, 51321062,
51233004 and 51390484).
References
[1] S. Stewart, S. Barr, J. Engiles, N.J. Hickok, I.M. Shapiro, D.W.
Richardson, J. Parvizi, T.P. Schaer, Vancomycin-modied implant
surface inhibits biolm formation and supports bone-healing in
an infected osteotomy model in sheep, J. Bone Joint Surg. Am. 94
(2012) 14061415.
[2] F. Zheng, S. Wang, S. Wen, M. Shen, M. Zhu, X. Shi,
Characterization and antibacterial activity of amoxicillin-loaded
electrospun nano-hydroxyapatite/poly(lactic-co-glycolic acid)
composite nanobers, Biomaterials 34 (2013) 14021412.
doi:10.1016/j.jconrel.2015.05.153

Preparation of cationic lipid layered PLGA hybrid nanoparticles


for gene delivery
Rajendran J.C. Bosea,b, Jong-Chan Ahna, Arai Yoshiea, Seah Parka,
Hansoo Parkb,*, Soo-Hong Leea,*
a
Department of Biomedical Science, CHA University, Gyeonggi-Do 463840, Republic of Korea
b
School of Integrative Engineering, Chung Ang University, Heukseok-dong,
Dongjak-gu, Seoul, Republic of Korea
Corresponding authors.
E-mail addresses: jaisangi14@cau.ac.kr (R.J.C. Bose), heyshoo@cau.ac.kr
(H. Park), soohong@cha.ac.kr (S.-H. Lee).
Recently, hybrid nanoparticles (NPs) consisting of various
materials and systems have been investigated to enhance delivery
and efcacy of DNA and RNA [1]. Among them, lipidpolymer hybrid
nanoparticles (LPHNPs) comprising a polymer core and lipid/lipid-

Abstracts / Journal of Controlled Release 213 (2015) e8e152

PEG shell are one of the versatile carriers due to their complementary characteristics of both polymeric nanoparticles and liposomes
[2]. In this study, we fabricated protamine incorporated cationic
DOTAP lipid layered PLGA hybrid nanoparticles (LPHNPs) as a gene
delivery system by convenient double emulsion solvent evaporation
method and examined the effect of lipid concentration on the
properties of LPHNPs (i.e. size). DLS results conrmed relatively
monodisperse LPHNPs with a Z-average size of 153 nm and low
polydispersity (PDI-0.07) and TEM result conrmed the structure of
a hydrophobic PLGA core and cationic lipid shell (Fig. 1). The zeta
potential shifted from a negative value ( 24 mV) to a positive value
(+60) with the incorporation of cationic lipid on the surface of
PLGA, which was probably induced by the hydrophobic interaction
between lipids and PLGA. We also found that the size and surface
charge of LPHNPs increased with the increase of cationic lipid
concentration indicating easy modulation of the surface properties of
LPHNPs. Long term stability of those complexes was also observed.
Additionally, transfection and viability of HEK 293 cells treated with
LPHNPs/DNA complexes with different concentrations were evaluated by ow cytometry. In all concentrations, LPHNPs/DNA complexes
exhibited strong transfection efciency while maintaining high cell
viability, suggesting LPHNPs as an excellent and versatile gene
delivery system.

Fig. 1. TEM images of lipid polymer nanoparticle and size graph with undersize curve
(upper), the zeta potential of bare PLGA and LPHNPs (scale bar50 nm).

e93

Biodegradable poly(ethylene glycol) methyl ether acrylate-bpoly(l-lysine)-b-poly(l-histidine) triblock copolypeptides for


non-viral gene delivery
Renjith P. Johnsona, Saji Uthamanb,c, Johnson V. Johna, Hye Ri Leea,
In Kyu Parkb,c, Il Kima,*
a
BK21 PLUS Center for Advanced Chemical Technology, Department of
Polymer Science and Engineering, Pusan National University, Pusan
609-735, Republic of Korea
b
Department of Biomedical Science, Chonnam National University
Medical School, 160 Baekseo-ro, Gwanju 501-746, Republic of Korea
c
BK 21 PLUS Center for Creative Biomedical Scientists, Chonnam
National University Medical School, 160 Baekseo-ro, Gwanju 501-746,
Republic of Korea
Corresponding author.
E-mail addresses: rpj111@pusan.ac.kr (R.P. Johnson),
ilkim@pusan.ac.kr (I. Kim).
The development of biodegradable cationic polymers for gene
delivery is desirable to circumvent the drawbacks of the viral vectors
[1]. Additionally, degradable polymers have the potential to overcome cellular toxicities that are related to the high charge densities
of the polycationic delivery system [2]. Therefore, to produce a
biocompatible delivery vehicle, we have designed novel biodegradable triblock copolymers consisting of repeating units of poly(ethylene glycol) methyl ether acrylate (PEGA) conjugated to cationic
poly(l-lysine) (p(Lys)) and poly(l-histidine) (p(His)) with different
chain lengths [p(PEGA)30-b-p(Lys)100-b-p(His)n] (n = 25, 50, 75,
100) via the combination of reversible addition fragmentation
transfer polymerization, ring opening polymerization of -amino
acid N-carboxyanhydrides and click cycloaddition reactions.
PEGA was used to impart steric stabilization properties onto the
polymer/pDNA complexes, and to improve the endosome-disrupting
capability, p(His) of various chain lengths were introduced. In order
to check the ability of the polymer to deliver nucleic acids, plasmid
DNA was condensed into polyplex with an average particle size
between 150 and 200 nm and with a surface charge of 445 mV. The
polymer exhibited very low in vitro cytotoxicity and demonstrated
efcient transfection along with intracellular gene expression
capability (Fig. 1). Thus, the present approach towards the synthesis
of block copolymers provides a means for developing versatile gene
delivery vectors harbouring the ideal requirements of low cytotoxicity, good stability, and high transfection efciency.

Keywords: smart nanodelivery, self-assembly, cationic lipids, therapeutic


delivery system
Acknowledgments
This research was supported by the National Research Foundation
of Korea (NRF-2012M3A9B4028569 and NRF-2013R1A2A1A09013
980).
References
[1] B. Mandal, H. Bhattacharjee, N. Mittal, H. Sah, P. Balabathula,
L.A. Thoma, G.C. Wood, Coreshell-type lipidpolymer hybrid
nanoparticles as a drug delivery platform, Nanomed.
Nanotechnol. 9 (2013) 474491.
[2] Q. Zhong, D.M. Chinta, S. Pamujula, H. Wang, X. Yao, T.K.
Mandal, R.B. Luftig, Optimization of DNA delivery by three
classes of hybrid nanoparticle/DNA complexes, J. Nanobiotech. 8
(2010) 6.

Fig. 1. Conceptual diagram of pDNA gene delivery using p(PEGA)30-b-p(Lys)100-bp(His)n.

doi:10.1016/j.jconrel.2015.05.154

Acknowledgements
This work was supported by the Fusion Research Program for Green
Technologies through the National Research Foundation of Korea

Keywords: cationic block copolymers, gene delivery, polypeptide,


polyplex

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