Abstract:
This study develops an ion exclusion chromatography method using polyethyleneimine-modified spongy monoliths to overcome the strong adsorption of RNA lipid nanoparticles to conventional separation media. The modified monoliths enabled rapid, charge-based resolution of distinct nanoparticle subpopulations and were integrated into a two dimensional LC/MS workflow for online lipid composition analysis. The later-eluting particles showed lower molar ratios of the ionizable lipid SM-102, demonstrating that surface charge heterogeneity directly reflects compositional differences. The method also served as a stability assay, revealing structural and compositional changes in formulations subjected to repeated freeze thaw cycles.
Authors:
Brady W. Drennan, Phat T. Dinh, Rebecca L. Taylor, Kevin A. Schug