Prolonged gene silencing by siRNA/chitosan-g-deoxycholic acid polyplexes loaded within biodegradable polymer nanoparticles

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Recently, small interfering RNA (siRNA) has received much attention for therapeutic applications; however, low transfection efficiency and intrinsic instability limit effective gene silencing. Here we show a new approach based on the incorporation of siRNA/polyelectrolyte complexes into biodegradable poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles to stabilize siRNA within a hydrophobic solid matrix for prolonged gene silencing. To solubilize siRNA in organic media, chitosan oligosaccharides grafted with deoxycholic acids are synthesized and complexed with siRNA, generating a self-assembled polyelectrolyte complex of 123.9 +/- 56.8 nm in diameter. The complex is mixed with PLGA solution and emulsified in water to prepare siRNA-loaded PLGA nanoparticles having a diameter of about 230 nm. The excellent structural stability of the prepared nanoparticles leads to efficient cellular uptake followed by effective gene silencing even in the presence of serum proteins. These results suggest that the encapsulation of siRNA into biodegradable polymer matrix can be an effective means of improving the structural stability of siRNA for prolonged therapeutic efficacy. (C) 2012 Elsevier B. V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2012-09
Language
English
Article Type
Article
Keywords

POLYELECTROLYTE COMPLEX MICELLES; PLGA NANOPARTICLES; LIGHT-SCATTERING; SIRNA DELIVERY; CHITOSAN; CONJUGATE; EFFICIENT; MICROSPHERES; WATER; RNA

Citation

JOURNAL OF CONTROLLED RELEASE, v.162, no.2, pp.407 - 413

ISSN
0168-3659
DOI
10.1016/j.jconrel.2012.07.006
URI
http://hdl.handle.net/10203/104062
Appears in Collection
BS-Journal Papers(저널논문)MS-Journal Papers(저널논문)
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