Lipid nanoparticle (LNP) drug delivery systems have taken on a leading role in the nanomedicine field, and especially so during the COVID-19 pandemic, as the Comirnaty (Pfizer/BioNTech) and Spikevax (Moderna) vaccines are comprised of mRNA delivery lipid nanoparticles. With this increased interest in LNPs and liposomes, the research is being pushed toward more complex lipid nanoparticles that combine drug delivery with diagnostics (theranostics), active targeting, multimodal therapeutics, targeted drug release and so on. With this in mind, what is lacking in this area are better analytical methods to investigate these carriers, and further, a description of how loaded LNPs differ from their “empty” counterparts. In this work, we present a quantitative liquid chromatography-tandem mass spectroscopy (LC-MSMS) method used to analyse various LNP compositions with different cargos (RNA and DNA, hydrophilic and hydrophobic drugs) to determine the relative lipid composition before and after drug loading. Phospholipids, ionizable lipids, PEGylated lipids, triglycerides and cholesterol will be the LNP building blocks quantified with this method. Different formulation methods will also be explored in order to draw conclusions about the self-assembly of LNPs.

Investigating the composition of lipid nanoparticles upon loading by LC-MSMS

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ACS Fall 2022

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