Hydrophobic modifications of cationic polymers for gene delivery

Cationic polymers are the subject of intense research as non-viral gene delivery systems, due to their flexible properties, facile synthesis, robustness, and proven gene delivery efficiency. Nevertheless, low transfection efficiency and undesirable cytotoxicity remain the most challenging aspects of these cationic polymers. To overcome the disadvantages, various modifications have been made to improve their gene delivery efficacy. Among them, hydrophobic modifications of the cationic polymers are receiving more and more attention. Most studies have shown that incorporation of hydrophobic chains can improve gene delivery efficiency, mainly explained by hydrophobic interaction conferred to the resulting amphiphilic polycation derivatives and by the enhanced cellular uptake by the hydrophobic chains via the lipophilic cell membrane. This review discusses recent studies on the hydrophobic modifications of cationic polymers for gene delivery. The effects of the hydrophobic modifications are discussed in terms of critical issues in the gene delivery process, such as gene encapsulation, adsorption to cell membrane, serum inhibition, gene dissociation, cytotoxicity, and tissue-targeting. Moreover, various hydrophobic modifications of the main cationic polymeric gene carriers (polyethylenimine, chitosan, polylysine, etc.) are described with regards to the resulting gene delivery activity. The structure-function relationships discussed here provide important information and insight for the design of novel gene vectors. (C) 2010 Elsevier Ltd. All rights reserved.