Characterization of poly((N-trimethylammonium) ethyl methacrylate)-based gene delivery systems

We have synthesized a hydrophilic cationic homopolymer of N-trimethylammonium ethyl methacrylate chloride (pTMAEM) and its copolymers with 1-vinyl-2-pyrrolidone (VP) and methyl methacrylate (MMA) at various monomer ratios and examined the physicochemical and biological characteristics of polymer/DNA complexes. All the (co)polymers were able to condense DNA to small particles and protect it from nuclease degradation. The particle size of pTMAEM/DNA complexes was smaller (550-175 nm) than the other polymers (1200-300 nm) tested. The zeta potential of the complexes was increased with increasing (co)polymer/DNA weight ratios and reached the constant value. The plateau value slightly decreased from +28 mV to +21 mV (P > 0.05) when the monomer content was increased. The optimal transfection efficiency of pTMAEM/DNA (655 mU/mg protein) was found at 0.5 polymer/DNA weight ratio and was reduced with increasing weight ratios due to increased cytotoxicity. The maximum transfection efficiency of copolymer/DNA was observed at a weight ratio of one and transfection efficiency slightly decreased with increasing monomer content in the copolymers. Overall, pTMAEM-VP/DNA complexes showed reduced cytotoxicity and increased transfection efficiency as compared with the other (co)polymers tested.