Effect of cationic lipid type in cationic liposomes for siRNA delivery into the liver by sequential injection of chondroitin sulfate and cationic lipoplex

Abstract

Previously, we reported that intravenous injection of chondroitin sulfate (CS), followed by intravenous injection of cationic liposome/siRNA complex (cationic lipoplex) could deliver siRNA into the liver. In this study, we examined the effects of the type of cationic lipid in the liposome on siRNA delivery into the liver. We used 6 types of cationic cholesterol derivatives and 11 types of dialkyl or trialkyl cationic lipids, and prepared 17 types of cationic liposomes to evaluate the gene-silencing effect of siRNA in mouse liver following sequential injection of CS plus cationic lipoplex. In 14 types of cationic liposomes, siRNA was accumulated in the liver when cationic lipoplexes were injected immediately after CS. However, suppression of apolipoprotein B (ApoB) mRNA expression in the liver and reduction of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol level in the serum were observed only after sequential injection of CS plus ApoB siRNA lipoplex with cationic liposomes composed of N-hexadecyl-N,N-dimethylhexadecan-1-aminium bromide (DC-1-16)/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and N,N-dimethyl-N-octadecyloctadecan-1-aminium bromide (DC-1-18)/DOPE. Based on these findings, the type of cationic lipid strongly affected the gene-silencing effect of siRNA in the liver by sequential injection of CS plus cationic lipoplex.