High-throughput quantification of drug loading into advanced delivery systems at the single particle scale

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Diseases that affect the skeletal system can be particularly difficult to treat. To enhance drug targeting, attempts have been made to engineer synthetic lipid-based nanoparticle drug delivery systems (DDS, e.g. liposomes). Over the last 25 years, advancements have occurred by varying lipid composition or by engineering the nanoparticle surface through the attachment of tissue-targeting ligands such as antibodies. Nonetheless, biodistribution studies have shown that most of these particles accumulate in the liver (<70%) with a maximum of 0.7% uptake observed in clinical targets. Our bodies have evolved natural networks for the targeted exchange of biological materials. These sophisticated nanoparticle carriers, termed extracellular vesicles, are naturally adapted to avoid clearance by the immune system and traverse complex biological barriers that prohibit the crossing of up to 98% of small molecule drugs. As such, EVs offer a novel and biocompatible alternative for advanced drug delivery that provide enhanced selectivity at sites that are currently difficult or even impossible to reach. Despite the advantages offered by EV technologies, attempts to exploit these particles for the delivery of therapeutic cargos are limited due to a lack of high-throughput analytical methods capable of accurately quantifying drug loading efficiency and localisation. This interdisciplinary project will adapt and optimise a state-of-the-art nano-flow cytometry platform (NanoFCM) to develop a future high-throughput technique capable of quantifying drug loading at the nano-scale.