Chitosan has been extensively studied as a genetic drug delivery platform. However,\nits efficiency is limited by the strength of DNA and RNA binding. Expecting a reduced binding\nstrength of cargo with chitosan, we proposed including heparin as a competing polyanion in the\npolyplexes. We developed chitosanâ??heparin nanoparticles by a one-step process for the local delivery\nof oligonucleotides. The size of the polyplexes was dependent on the mass ratio of polycation\nto polyanion. The mechanism of oligonucleotide release was pH-dependent and associated with\npolyplex swelling and collapse of the polysaccharide network. Inclusion of heparin enhanced\nthe oligonucleotide release from the chitosan-based polyplexes. Furthermore, heparin reduced\nthe toxicity of polyplexes in the cultured cells. The cell uptake of chitosanâ??heparin polyplexes\nwas equal to that of chitosan polyplexes, but heparin increased the transfection eciency of the\npolyplexes two-fold. The application of chitosanâ??heparin small interfering RNA (siRNA) targeted\nto vascular endothelial growth factor (VEGF) silencing of ARPE-19 cells was 25% higher. Overall,\nchitosan-heparin polyplexes showed a significant improvement of gene release inside the cells,\ntransfection, and gene silencing efficiency in vitro, suggesting that this fundamental strategy can\nfurther improve the transfection efficiency with application of non-viral vectors.
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