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Fine tuning of mixed ionic and hydrogen bond interactions for plasmid delivery using lipoplexes

Abstract : Non viral gene transfection has been mostly reached via cationic polymer and lipid, required for DNA complexation and cell internalisation. However, cationic charges often induce cytotoxicity and limit the efficacy of the lipoplexes in vivo due to their fast elimination from the blood stream. Few years ago, we had developed noncationic lipid interacting with DNA via hydrogen bond interactions. To take advantage of both the internalisation efficacy of cationic complexes and the higher DNA release efficacy of non cationic lipids, we chose to mix both ionic and hydrogen bond interactions within one lipoplex. The idea behind this strategy would be to reduce the overall charge while maintaining a high level of transfection. Four mixed formulations of cationic lipid and thiourea lipid were prepared. We found that decreasing ionic interactions and increasing hydrogen bond interactions improved cationic lipoplexes properties. Indeed, we showed that replacement of net positive charges by hydrogen bond interactions with DNA phosphates led to efficient lipoplexes for in vitro DNA transfection at lower cationic charge content, which consequently reduced lipoplex cytotoxicity. (C) 2014 Elsevier B.V. All rights reserved.
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Johanne Seguin, Helene Dhotel, Rene Kai-Luen, Michel Bessodes, Nathalie Mignet. Fine tuning of mixed ionic and hydrogen bond interactions for plasmid delivery using lipoplexes. European Journal of Pharmaceutics and Biopharmaceutics, Elsevier, 2015, 90, pp.63-69. ⟨10.1016/j.ejpb.2014.11.001⟩. ⟨hal-03290551⟩



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