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Bcl-2, an antiapoptotic protein, is considered as a potential target in cancer treatment since its oncogenic potential has been proven and is well documented. Antisense technology and RNA interference (RNAi) have been used to reduce the expression of the Bcl-2 gene in many types of cancer cells and are effective as adjuvant therapy along with the chemotherapeutic agents. The lack of appropriate delivery systems is considered to be the main hurdle associated with the RNAi. In this review, we discuss the antiapoptotic Bcl-2 protein, its oncogenic potential, and various approaches utilized to target Bcl-2 including suitable delivery systems employed for successful delivery of siRNA.

Potential use of siRNA as therapeutic agent has elicited a great deal of interest. However, insufficient cellular uptake and poor stability limited its application in therapeutics. In our earlier study, we prepared PLGA nanoparticles for effective delivery of siRNA targeting Bcl-2 gene to block its expression. Purpose of the present study was to improve effectiveness of PLGA nanoformulation of siRNA targeting anti-apoptotic Bcl-2 gene through chitosan coating. We prepared chitosan coated PLGA nanoparticles by using the double emulsion solvent diffusion (DESE) method. Characterization of prepared chitosan coated nanoformulation was done followed by cytotoxicity studies, expression studies and in vivo studies. Particle size of chitosan coated nanoparticles was found to be increased compared to PLGA nanoparticles from 244 to 319 nm. Surface charge of chitosan coated nanoparticles was found to be positive facilitating transfection of nanoformulation into cells. In vitro studies indicated increased transfection of nanoparticles resulting in effective silencing of Bcl-2. Marked apoptotic lesions were observed in nuclear staining studies. On comparison of the results from the present study with those of previous study, it was found that the extent of silencing of Bcl-2 gene by PLGA nanoformulation has improved significantly through chitosan coating. In vivo studies showed significant tumor regression in animals treated with chitosan coated PLGA nanoformulation of siRNA., (Copyright © 2012 Elsevier B.V. All rights reserved.)