Impact of the nature, size and chain topologies of carbohydrate–phosphorylcholine polymeric gene delivery systems

With the recent significant advances in the field polymer chemistry, it is now possible to produce well-defined and non-toxic cationic polymers with advanced molecular structures of desired molecular weights and compositions. Carefully engineered polymer architectures are found to impact significantly their DNA condensation and gene delivery efficacies. In a previous study, the statistical carbohydrates based copolymers were found to show high gene expression and low toxicity, however there aggregation in the presence of serum proteins was a major drawback. In this study, carbohydrate and phosphorylcholine based cationic polymers having a different architecture, compositions and varying molecular weights are produced and are termed as cationic ‘block-statistical’ copolymers. These cationic copolymers are evaluated for their gene delivery efficacies, interactions with serum protein, cellular uptake and nuclear localization ability. As compared to the statistical analogue, ‘block-statistical’ copolymers showed high gene expression, low interactions with serum proteins, as well as low toxicity in hepatocytes and human dermal fibroblasts. In addition, 2- methacryloyloxyethyl phosphorylcholine (MPC) based ‘block-statistical’ copolymers and their sugar incorporated analogues were prepared and were found to serve as improved gene delivery vectors than their statistical analogues.