کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2083411 | 1545335 | 2015 | 7 صفحه PDF | دانلود رایگان |
• Mixed lipoplexes were formed between cationic lipids, lipothiourea lipids and DNA.
• Lipoplexes involved hydrostatic and hydrogen bonds to condense DNA.
• Hydrogen bonds allowed to reduce the overall cationic content of the lipoplexes.
• This mixture increased DNA transfection at lower cationic charge content.
• The cytotoxicity was reduced as compared to cationic lipoplexes.
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.
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Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 90, February 2015, Pages 63–69