Investigating the Efficiency of Ionic Lipids as Drug Delivery Systems

Abstract

With the appearance of the SARS-CoV2 virus, mRNA vaccines have taken the spotlight, showing high clinical safety and efficacy. These vaccines utilize nanoparticle drug delivery systems to package the mRNA and deliver them to target cells. However, the vaccines generally require high doses in order to ensure enough viable mRNA is delivered to the endpoint. One of the main challenges appears to be the release of sufficient amounts of mRNA once the cells endocytose the nanoparticles. Ionizable lipids and lipid bilayers release the mRNA in an undercharacterized process. We hypothesize that ionizable lipids will release from the coded mRNA when water competes with them for interaction with the mRNA. Since poorly packing ionizable lipids would allow more water to interact with the mRNA, they should be the most effective delivery lipids. We modeled monolayer packing of several known ionizable lipids using Packmol. The carbon density of these monolayers was analyzed and correlated with mRNA delivery efficiency. We comment on the potential applications for improving mRNA delivery based on these results.