Preparation and characterization of chitosan/polyguluronate nanoparticles for siRNA delivery

Small interfering RNA (siRNA) has been widely investigated as a potential therapeutic for treatment of various diseases. However, the use of siRNA is limited due to its rapid degradation and low intracellular association in vitro and in vivo. Chitosan nanoparticles encapsulating siRNA were prepared using a coacervation method in the presence of polyguluronate (PG), which is isolated from alginate and is strongly related to ionic interactions of negatively charged alginate. Various physicochemical properties of chitosan/PG nanoparticles, including size, surface charge, morphology, and interaction with siRNA, were characterized. The mean diameter of siRNA-loaded chitosan-based nanoparticles ranged from 110 to 430 nm, depending on the weight ratio between chitosan and siRNA. Nanoparticles showed low cytotoxicity and were useful in delivering siRNA to HEK 293FT and HeLa cells. Chitosan/PG nanoparticles were considered promising for siRNA delivery due to their low cytotoxicity and ability to transport siRNA into cells, which can effectively inhibit induction of targeting mRNA. (C) 2009 Elsevier B.V. All rights reserved.