Improvement of therapeutic efficacy of PLGA nanoformulation of siRNA targeting anti-apoptotic Bcl-2 through chitosan coating

Hitesh Vitthalbhai Jagani, Venkata Rao Josyula, Vasanth Raj Palanimuthu, Raghu Chandrashekar Hariharapura, Sagar Shantimal Gang

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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. © 2013 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)611-618
Number of pages8
JournalEuropean journal of pharmaceutical sciences
Volume48
Issue number4-5
DOIs
Publication statusPublished - 12 Mar 2013

Keywords

  • Apoptosis
  • Bcl-2 and cancer
  • Chitosan
  • Poly (d,l-lactide-co-glycolide)
  • siRNA

Fingerprint Dive into the research topics of 'Improvement of therapeutic efficacy of PLGA nanoformulation of siRNA targeting anti-apoptotic Bcl-2 through chitosan coating'. Together they form a unique fingerprint.

  • Cite this