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

Duncan Casey, Kalypso Charalambous, Antony Gee, Robert V. Law, Oscar Ces*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

14 Citations (Scopus)
264 Downloads (Pure)

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.

Original languageEnglish
Article number20131062
Number of pages7
JournalJournal of the Royal Society Interface
Volume11
Issue number94
Early online date12 Mar 2014
DOIs
Publication statusPublished - 6 May 2014

Keywords

  • Drug transport
  • High-performance liquid chromatography
  • Lipid hydrolysis
  • Membrane biophysics

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