The use of orthogonal analytical approaches to profile lipid nanoparticle physicochemical attributes

Abstract

Abstract Lipid nanoparticles have become a major disruptor within the drug delivery field of complex RNA molecules. The wide applicability of prototype nanomedicines have the potential to fill clinical requirements against current untreatable diseases. The uptake and implementation of analytical technologies to evaluate these prototype nanomedicines have not experienced similar growth rates hindering the translation of LNPs. Here, we evaluate a model RNA-LNP formulation with a selection of routine, and high-resolution orthogonal analytical techniques across studies on manufacturing process parameter impact and formulation stability evaluation under refrigerated and ultra-low temperatures. We analysed model cationic RNA complexed lipid nanoparticle formulation through process impact on formulation critical quality attributes, short term refrigerated stability evaluation, and frozen storage stability using zetasizer dynamic light scattering and nanoparticle tracking analysis. We also evaluated freeze/thaw induced stress on LNP formulation using high resolution field-flow fractionation. Statistical analysis and correlations between techniques were drawn to further enhance our understanding of LNP formulation design, and physiochemical attributes to facilitate LNP formulation clinical translation.