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Chitosan as a carrier for targeted delivery of small interfering RNA

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 399, Issue 1-2, Pages 1-11

Publisher

ELSEVIER
DOI: 10.1016/j.ijpharm.2010.08.022

Keywords

siRNA; Chitosan; Targeted delivery; Nanoparticles

Funding

  1. CSIR, New Delhi, India [21(0760)/09/EMR-II]
  2. Research Corporation [6576]
  3. Welch Foundation [AI0045]

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The recent discovery of RNA interference (RNAi) technology for gene therapy has triggered extensive research efforts for developing small interfering RNA (siRNA) loaded nanocomplexes of chitosan and its derivatives for silencing genes. Due to its large molecular weight (similar to 13 kDa) and polyanionic nature (similar to 40 negative phosphate groups), naked siRNA does not freely cross the cell membrane. Therefore, its efficient intracellular delivery requires suitable carriers to overcome the intrinsic, poor intracellular uptake and limited blood stability. Among viral and non-viral delivery vectors, the use of non-viral vectors such as chitosan or its derivatives is attractive, since these polymers are biodegradable, biocompatible, with low toxicity and high cationic potential. Even though much of the technology-base has been well established for targeted delivery of plasmid DNA using chitosan and its derivatives, only recently, has the technology been applied to the targeted delivery of siRNA. This review will explore the factors that are most important in enhancing transfection efficiency and cell specificity in vitro and in vivo including degree of deacetylation, molecular weight and chemical modification of chitosan, pH, and the charge ratio of chitosan to siRNA. (C) 2010 Elsevier B.V. All rights reserved.

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