Chitosan as a carrier for targeted delivery of small interfering RNA.
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 (∼13 kDa) and polyanionic nature (∼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.
Rudzinski
Walter E
WE
Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA. wr01@txstate.edu
Aminabhavi
Tejraj M
TM
D000818:Animals; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008970:Molecular Weight; D053761:Nanocomposites / Q000737:chemistry*; D010957:Plasmids; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection
D004337:Drug Carriers; D034741:RNA, Small Interfering; D048271:Chitosan