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

Posted on February 03, 2022

Gene Silencing Post Square

siRNA are small double-stranded RNAs that are capable of suppressing the expression of specific genes. They do this by degrading mRNA after transcription. As highly specific as they are, they are perfect therapeutic agents for the silencing of disease-causing gene expression. There are several problems that must be overcome to deliver siRNA through the plasma membrane due to hydrophilicity and large size. Also, siRNA is immediately degraded by RNase when circulating in the blood. As such, it’s easy to see the importance of the perfect delivery system for shuttling these highly specific therapeutic agents into cellular environments.

A recent study found that intravenously injecting chondroitin sulfate (CS) followed by cationic lipoplexes resulted in the efficient delivery of siRNA to liver cells. The initial study did not identify whether the cationic lipid used in the cationic lipoplexes affected the biodistribution and gene-silencing effects of the encapsulated siRNA. So, to answer these questions the team started an additional study to investigate the affect that different cationic lipids would have on these factors. They selected 6 cholesterol derived cationic lipids and 11 di- or tri-alkyl cationic lipids and prepared 17 cationic liposomes containing DOPE.

DOPE was chosen for its ability to promote endosomal release of cationic lipoplexes via increased interactions between the liposomal and endosomal membranes. Charge ratios for the lipoplexes were 7:1 (+:-) for those containing cholesterol based cationic lipids and 4:1 (+:-) for those containing alkyl based cationic lipids. Before mixing with siRNA the cationic lipoplexes were between 70-120 nm in size with a zeta potential of 43-58 mV. After the siRNA was mixed with the cationic lipoplexes, the size increased to 100-200 nm and the zeta potential decreased to 37-51 mV.

The biodistribution of siRNA after injection was evaluated using a Cy5.5 labelled siRNA. The type of cationic lipid used in the liposomal formula was proven to play a key role in where the siRNA would likely accumulate, either the lungs, kidneys, or liver. Furthermore, they proved that the cationic lipid used in the lipoplexes also affected the gene-silencing effects of the therapeutic agent. After these experiments, they determined that DC-1-16 and DC-1-18 induced the accumulation of siRNA in the liver after sequential injection with CS. The study suggests that these cationic lipids combined with DOPE create an outstanding siRNA delivery tool.

If your research calls for a cationic liposomal formula to get siRNA where it needs to go, you’re already in the right place! Avanti’s DOPE will be the highest grade you can find anywhere and we offer a wide variety of Cationic Lipids. Click HERE to find out more! And if you would like to read the full research article published in the Journal of Drug Delivery Science and Technology, click the link!

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