Amphiphilic drug interactions with model cellular membranes are influenced by lipid chain-melting temperature

Small-molecule amphiphilic species such as many drug molecules frequently exhibit low-to-negligible aqueous solubility, and generally have no identified transport proteins assisting their distribution, yet are able to rapidly penetrate significant distances into patient tissue and even cross the blood-brain barrier. Previous work has identified a mechanism of translocation driven by acid-catalysed lipid hydrolysis of biological membranes, a process which is catalysed by the presence of cationic amphiphilic drug molecules. In this study, the interactions of raclopride, a model amphiphilic drug, were investigated with mixtures of biologically relevant lipids across a range of compositions, revealing the influence of the chain-melting temperature of the lipids upon the rate of acyl hydrolysis.