Reducible Amino Acid Based Cationic Lipids as Highly Efficient and Serum‐Tolerant Gene Vectors

In this study, two cationic lipids, each containing an α-tocopherol moiety and a biocompatible amino acid headgroup (histidine or lysine) linked through a biodegradable disulfide and carbamate bond, were prepared and evaluated in cell culture as nonviral gene delivery vectors. The physicochemical properties of these lipids, including size, zeta potential and cellular uptake of the lipoplexes formed with DNA, as well as the transfection efficacy (TE), were investigated. The results show that the chemical structure of the cationic headgroup affects the physicochemical parameters of these amino acid based lipids and especially the TE. In addition to their low cytotoxicity, these lipoplexes also showed comparable TE with the commercially available Lipofectamine 2000. The TE of the cationic lipid based on histidine was especially high, and was 4.3 times higher than that of a branched polyethylenimine in the presence of 10 % serum. These results demonstrate the promise of amino acid based lipids for safe and efficient gene delivery.