Presence of vesicles in clinically relevant lipid nanoparticle formulations: quantifying sub-populations and effect of interactions on structure

The use of lipid nanoparticles (LNPs) and vesicles for drug delivery is a rapidly growing field. Although LNPs and vesicles have been successfully applied in clinical settings, rational design of LNP and vesicle formulations is challenging due to limited understanding of structure-function relationships, LNP uptake mechanisms and their interactions with cellular machinery in biological samples. Understanding structure-function relationships of LNPs is challenging, due to the sample heterogeneity, which is often present in formulations as a vesicle sub-population. Due to the complex nature of the cellular environment and composition of biomembranes, understanding of these processes in vitro is limited. In a continuation of a previous experiment, we will use SANS to characterise known mixtures of LNPs and synthetic vesicles with high LNP:vesicle ratios, in order to quantify vesicle sub-populations, and mixtures of LNPs and biomimetic vesicles. We will follow the structural changes of these mixtures over time. For the high LNP:V mixtures, these structural changes are relevant for LNP post-formulation stability. For the LNP:biomimetic vesicle mixtures, these interaction induced structural changes could precede membrane remodelling and cargo release in biological systems. Together, these results contribute to the understanding of structural heterogeneity within LNP formulations and the mechanisms of LNP drug delivery in biological systems.