Influence of cholesterol content on the interaction of LNPs with model endosomal membranes

There has been a shift in the pharma industry towards development of medicines acting within the cell, typically in the cytosol, thereby creating demand for advanced delivery vehicles such as lipid nanoparticles (LNPs) that deliver their payload intracellularly. Generally, these vehicles are taken into the cell's endosome via a process known as endocytosis. In order for the therapeutic agent to exert its effect, the vehicle (and its payload) must escape the endosome, releasing the payload into the cytosol. Currently only 2% of vehicles are released into the cytosol. This study wishes to determine the effect of the concentration of cholesterol present in the LNPs on their interaction with a model endosomal membranes (EMM) using neutron reflectivity in combination with contrast variation. In particular the amount of cholesterol leaving the LNP and entering the EMM will be determined. This knowledge will enable the development of improved LNPs that more efficiently deliver their therapeutic payload.