Effect of cationic lipid type in PEGylated liposomes on siRNA delivery following the intravenous injection of siRNA lipoplexes

For the systemic injection of cationic liposome/small interfering RNA (siRNA) complexes (cationic lipoplexes), the polyethylene glycol (PEG)‑modification (PEGylation) of the lipoplexes can enhance their systemic stability. However, PEGylation reduces the efficiency of siRNA‑mediated gene silencing by cationic lipoplexes. In this study, in order to examine the effects of cationic lipids in PEGylated liposomes on gene‑silencing effects following the systemic injection of PEGylated lipoplexes, we used 4 types of cationic cholesterol derivatives and 3 types of dialkyl or trialkyl cationic lipids, and prepared 7 types of PEGylated cationic lipoplexes that contained 1 mol% PEG2000‑DSPE. The PEGylation of lipoplexes decreased their agglutination with erythrocytes. As regards siRNA biodistribution and the in vivo gene‑silencing effects, intravenous injections of PEGylated lipoplexes with cationic cholesterol derivatives induced the accumulation of siRNAs in the liver, but they did not suppress the expression of a target gene. By contrast, those with dialkyl or trialkyl cationic lipids induced the accumulation of siRNAs in the lungs, and among these, PEGylated cationic lipoplexes with N,N‑dimethyl‑N‑octadecyloctadecan‑1‑aminium bromide (DC‑1‑18) significantly induced gene silencing effects in the lungs. On the whole, the findings of this study suggest that the biodistribution and gene silencing effects with siRNAs following the systemic injection of 1 mol% PEGylated lipoplexes are strongly affected by the type of cationic lipid. The selection of the cationic lipid in the liposomal formulation may thus be important for the successful in vivo delivery of siRNAs by PEGylated cationic liposomes.