Effect of chondroitin sulfate on siRNA biodistribution and gene silencing effect in mice after injection of siRNA lipoplexes

Abstract Previously, we found that intravenous injection of chondroitin sulfate (CS), followed by intravenous injection of siRNA/cationic liposome complexes (siRNA lipoplexes) could deliver siRNAs to the liver and suppress expression of target genes. Here, we examined the effect of injection order of CS and siRNA lipoplexes on the biodistribution of siRNA and gene silencing in the liver after sequential injection. When siRNA lipoplexes were injected intravenously into mice, the siRNA largely accumulated in the lungs. However, injection of siRNA lipoplexes, followed by injection of CS, reduced siRNA accumulation in the lungs and increased it in the liver. In addition, agglutinates of erythrocytes caused by the addition of siRNA lipoplexes were re-dispersed by the addition of CS, indicating that the agglutinates accumulating in the lungs by injection of siRNA lipoplexes were broken up by CS injection. However, injection of apolipoprotein B (ApoB) siRNA lipoplexes, followed by injection of CS did not suppress ApoB mRNA levels in the liver. From there results on sequential injection, the injection order of CS and siRNA lipoplexes was important for gene silencing effects in the liver, although the sequential injection could deliver siRNA efficiently into the liver regardless of the injection order of CS and siRNA lipoplexes.