Arginine-modified chitosan complexed with liposome systems for plasmid DNA delivery

In order to make more efficient chitosan-based nanoparticles for transfection in physiological condition, chitosomes composed of chitosan modified with arginine and complexed with DOTAP/DOPE lipids are synthesized (named chitosomes) by reverse phase evaporation technique. Structure analyses of chitosomes with or without plasmid DNA (pDNA) are performed by electrophoresis, zeta potential, dynamic light scattering, small angle X-ray scattering and isothermal titration calorimetry, and transfection efficiency and cytotoxicity are performed in HEK293 T cells. Chitosomes have a positive surface charge (X¯= 52 mV) with an average size of 116 nm, and interaction with pDNA are favored thermodynamically and do not suffer aggregation significantly. In our experimental conditions, the transfection efficiency average reaches 86% ± 3, while the Lipofectamine® reaches 87% ± 5 in vitro. Cytotoxicity of chitosomes are tolerable. Structural analyses show that that chitosomes-pDNA complexes appear to have multilamellar vesicle structures hosting pDNA in-between bilayers which favor interaction with cell membrane and delivery of pDNA. Results show that synthesized chitosomes are promising carriers for gene delivery.