Preparation and characterization of nonaarginine-modified chitosan nanoparticles for siRNA delivery

Chitosan-based nanoparticles have been widely used as a carrier for gene delivery due to their low toxicity and the positively charged amino groups in chitosan. In this study, we hypothesized that introduction of nonaarginine to chitosan could improve its ability to form a complex with siRNA, as well as enhance the cellular uptake and transfection efficiency of chitosan-based nanoparticles. To this end, a peptide with nine repeating arginine residues was chemically coupled to the chitosan backbone, and various characteristics of nonaarginine-chitosan/siRNA nanoparticles were investigated. The mean diameter and zeta potential of the nonaarginine-chitosan/siRNA nanoparticles were dependent on the amount of nonaarginine conjugated to chitosan. Nonaarginine-modified chitosan/siRNA nanoparticles demonstrated enhanced cellular association and transfection efficiency in vitro, while maintaining a low level of cytotoxicity. In conclusion, nonaarginine-modified chitosan should be considered a potential carrier for various gene delivery applications. (C) 2012 Elsevier Ltd. All rights reserved.