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Wytrwal M., Leduc C., Sarna M., Goncalves C., Kepczynski M., Midoux P., Nowakowska M., Pichon C.

Gene delivery efficiency and intracellular trafficking of novel poly(allylamine) derivatives

International Journal of Pharmaceutics (2015) 478 (1) 372-382 - doi : 10.1016/j.ijpharm.2014.11.053

par Frapart - publié le , mis à jour le

Abstract :

Non-viral gene carriers for safe and efficient gene transfection have become of particular interest among researchers of different disciplines ranging from physical chemistry to biotechnology. Recently polymeric vectors have been extensively studied as potentially new gene transfer agents. Until now most of the research efforts were made to optimize the gene-to-polymer weight ratio of polyplexes for safe and efficient gene transfection. In this work, we report on the development of novel poly(allylamine) derivatives with different balance of the primary, secondary, tertiary, and quaternary amino groups. All derivatives were able to complex pDNA into polyplexes at low gene-to-polymer weight ratios i.e., 1:1 or 1:2. Moreover, the examined polyplexes were less cytotoxic and showed better transfection efficiency when compared to linear poly(ethyleneimine). These results indicate that the presence of quaternary ammonium groups is important in the formation of stable polyplexes. Polymers with all types of amino groups showed large potential for gene delivery. Furthermore, polyplexes with such derivatives were well internalized by cells and ended up into acidic late endosomes. (C) 2014 Elsevier B.V. All rights reserved.