Evaluation of the injection route of an anionic polymer for small interfering RNA delivery into the liver by sequential injection of anionic polymer and cationic lipoplex of small interfering RNA

Previously, we developed a novel small interfering RNA (siRNA) transfer method for the liver by sequential intravenous injection of an anionic polymer and cationic liposome/siRNA complex (cationic lipoplex). In this study, we examined the effects of the type of anionic polymer and injection route of the anionic polymer on the biodistribution of siRNA after sequential injection of anionic polymer and cationic lipoplexes. When cationic lipoplexes were injected intravenously into mice, siRNA largely accumulated in the lungs. In contrast, sequential injection of cationic lipoplex after intravenous injection of 1 mg chondroitin sulfate C and A (CS-C and CS-A) or polyaspartic acid decreased the accumulation of siRNA in the lungs and increased it in the liver, compared with injection of cationic lipoplex. Regarding the injection route of the anionic polymer, intramuscular, intraperitoneal, or subcutaneous injection of 10 mg CS-C before intravenous injection of cationic lipoplex resulted in siRNA accumulation mainly in the liver. Furthermore, the injection of cationic lipoplex of apolipoprotein B (ApoB) siRNA after intravenous or intramuscular injection of CS-C could suppress ApoB mRNA levels in the liver. Sequential injection of CS-C plus cationic lipoplex could deliver siRNA efficiently into the liver regardless of the injection route of CS-C. (C) 2016 Elsevier B.V. All rights reserved.