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The development and mechanism studies of cationic chitosan-modified biodegradable PLGA nanoparticles for efficient siRNA drug delivery
Pharmaceutical research
  • Xudong Yuan
  • Bruhal Shah
  • Naimish K. Kotadia
  • Jian Li
  • Hua Gu
  • Zhiqian Wu, Philadelphia College of Osteopathic Medicine
Document Type
Article
Publication Date
1-1-2010
Abstract

Purpose: In order to improve siRNA delivery for possible clinical applications, we developed biodegradable chitosan-modified poly(D,L-lactide-co- glycolide) (CHT-PLGA) nanoparticles with positive surface charge, high siRNA loading, high transfection efficiency and low toxicity. Methods: CHT-PLGA nanoparticles were prepared, and siRNA was loaded by emulsion evaporation method with poly(vinyl alcohol) (PVA) as emulsifier. siRNA loading efficiency, particle size, and Zeta potential of nanoparticles were measured. Gel retardation and protection assays were conducted to determine the loading and binding of siRNA in the formulation. Cell transfection was performed to study in vitro siRNA silencing efficiency. XTT assay was used to evaluate the cytotoxicity. Results: It was found that the nanoparticle diameter and positive Zeta potential increase as the chitosan coating concentration increases. CHT-PLGA nanoparticles showed excellent siRNA binding ability and effective protection of oligos from RNase degradation. siRNA-loaded nanoparticles were successfully delivered into the HEK 293 T cell line, and the silencing of green fluorescence protein (GFP) expression was observed using fluorescent microscopy and flow cytometry. In addition, the cytotoxicity assay revealed that CHT-PLGA nanoparticles had relatively low cytotoxicity. Conclusion: This study suggests that biodegradable cationic CHT-PLGA nanoparticles possess great potential for efficient and safer siRNA delivery in future clinical applications.

Comments

This article was published in Pharmaceutical research, Volume 27, Issue 7, Pages 1285-1295.

The published version is available at http://dx.doi.org/10.1007/s11095-010-0103-0.

Copyright © 2010 Springer.

Citation Information
Xudong Yuan, Bruhal Shah, Naimish K. Kotadia, Jian Li, et al.. "The development and mechanism studies of cationic chitosan-modified biodegradable PLGA nanoparticles for efficient siRNA drug delivery" Pharmaceutical research Vol. 27 Iss. 7 (2010) p. 1285 - 1295
Available at: http://works.bepress.com/zhiqianjames_wu/6/