Understanding population heterogeneity of hybrid lipid and block co-polymer vesicles

Design of therapeutics in medicine is seeing a paradigm shift towards use of lipid nanoparticles (LNPs),and have transformed drug delivery by improving efficacy, reducing toxicity, and enhancing the solubility of drugs to target tissues. LNPs typically contain a PEGylated lipid to provide colloidal stability however it is known that lipids can be chemically and structurally labile which can cause leakage of cargo. We have shown that hybrid lipid-block copolymer nanoparticles offer synergistic properties that can be tuned across a broad parameter space. Addition of block copolymers leads to increased NP stability and less permeability, whilst the inclusion of lipids allows for greater biocompatibility. Importantly, NPs possess a complex and diverse range of physicochemical properties that can be difficult to characterise due to the presence of heterogeneity. The role that heterogeneity plays in terms of size, size dispersity, and morphology in biological performance is not fully understood, and can lead to issues in overall product performance and translation into clinical settings. This proposal aims to understand the extent of particle heterogeneity in hybrid lipid and block co-polymer vesicles, by the isolation of well-characterized fractions with a low to high polydispersity from an original polydisperse populations (<0.2) using Multi-Detector Asymmetric-Flow Field-Flow Fractionation and allow us to determine structure-function relationships