Abstract
In this study, we examined the effect of neutral helper lipids in cationic liposomes on gene silencing efficacy in the lungs after intravenous injection of cationic liposomes/siRNA complexes (siRNA lipoplexes) into mice. We used 6 kinds of dialkyl or trialkyl cationic lipids as cationic lipids and prepared cationic liposomes composed of each cationic lipid with 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), DOPE/cholesterol (Chol), or Chol. Regardless of the type of cationic lipid in the cationic liposomes, the increase in Chol content in the formulation decreased the in vitro gene silencing efficacy, and it increased siRNA accumulation in the lungs after intravenous injection of siRNA lipoplexes. However, gene silencing efficacies in the lungs were not greatly affected by the type of neutral helper lipid in cationic liposomes composed of cationic lipids with saturated dialkyl chains (C16–C18), although they were increased by the inclusion of Chol into formulations of cationic liposomes composed of cationic lipids with unsaturated dialkyl chains (C18). These findings indicated that siRNA biodistribution and in vivo knockdown efficiency after the intravenous injection of siRNA lipoplexes were strongly affected by combination of a cationic lipid and neutral helper lipid in cationic liposomes.
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