title: Amphiphilic drug interactions with model cellular membranes are influenced by lipid chain-melting temperature.
abstract: 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.
authors.affiliation: Institute of Chemical Biology, Imperial College, , Exhibition Road, London, UK.
authors.forename: Duncan
authors.initials: D
authors.lastname: Casey
authors.forename: Kalypso
authors.initials: K
authors.lastname: Charalambous
authors.forename: Antony
authors.initials: A
authors.lastname: Gee
authors.forename: Robert V
authors.initials: RV
authors.lastname: Law
authors.forename: Oscar
authors.initials: O
authors.lastname: Ces
mesh_terms: D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000737:chemistry; D006868:Hydrolysis; D008563:Membrane Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D008956:Models, Chemical; D020891:Raclopride / Q000737:chemistry*
chemical_list: D008563:Membrane Lipids; D008567:Membranes, Artificial; D020891:Raclopride
keywords: drug transport; high-performance liquid chromatography; lipid hydrolysis; membrane biophysics