Evaluation of cationic nanoparticles of biodegradable copolymers as siRNA delivery system for hepatitis B treatment


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Abstract

Cationic nanoparticles of biodegradable polymers such as poly (lactide) (PLA) have been shown to be promising carrier systems for DNA and siRNA delivery. However, the parameters which influence the transfection efficiency have not been investigated in details. In this work, four groups of cationic PLA-based nanoparticles were synthesized by the nanoprecipitation method and solvent evaporation method with polyethyleneimine (PEI) and chitosan as two types of surface coating materials. Cationic poly (D,L-lactide-co-glycolide) (PLGA)–PEI, PLGA–chitosan and methoxy poly (ethylene glycol)–poly (lactide) (mPEG)–PLA/PEI, mPEG–PLA–chitosan nanoparticles were characterized in terms of size and size distribution by laser scattering, surface charge by zeta potential measurement, and surface chemistry by X-ray electron spectroscopy (XPS). The four type pg nanoparticles were compared for their interaction with siRNA and nanoparticles mediated siRNA transfection efficiency with a hepatitis B model, where the inhibition effects of the double strand RNA (dsRNA) mediated by the four types of nanoparticles were evaluated by measuring the HBsAg expression level. The highest inhibition effect of HBsAg (the surface antigen of the hepatitis B Virus (HBV), which indicates current hepatitis B infection) expression was achieved by the mPEG–PLA–PEI nanoparticles mediated siRNA transfection. The results demonstrated that the siRNA delivery follows a size and surface charge dependant manner.

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