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Cationic Charged Polymer Vesicles from Amphiphilic PEI-g-PSSA-g-PEI as Potential Gene Delivery Vehicles

Polymer vesicles have attracted extensive interest for a variety of biomedical applications. Herein, novel polymer vesicles are prepared by the self-assembly of amphiphilic polyethyleneimine-g-poly(disulfide amine)-g-polyethyleneimine (PEI-g-PSSA-g-PEI) for gene delivery. To investigate the effect of hydrophobicity on transfection efficiency, a small series of PEI-g-PSSA-g-PEI were prepared under uniform conditions containing PEI fragments of the same molecular weight. The hydrophobicity of PEI-g-PSSA-g-PEI was adjusted by varying the hydrophobic content in the poly(disulfide amine) backbone and by choosing hydrophobic monomers ranging in length from C12 to C16. The hydrophobicity of polymers was also related to DNA binding affinity. Polymer vesicles obtained from the water-insoluble polymers condensed with DNA into polyplexes with sizes below 200 nm and surface charge ranging from +10 to +35 mV that were suitable for cell endocytosis. DNA polyplexes exhibited an inverted hexagonal structure, observed by transmission electron microscopy. The results of in vitro transfection demonstrate that the hydrophobic–hydrophilic balance of copolymers greatly affects their transfection properties. The top-performing polymer, II-70 %, showed improved transfection efficiency and significantly lower cytotoxicity on COS-7 cells when compared with commercial reagents polyethyleneimine (PEI 25K) and Lipofectamine 2000. These results indicate that cationic polymer vesicles with tunable hydrophobicity are promising materials for gene delivery.