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

doi:10.1098/rsif.2013.1062

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 journal › Article › peer-review

24 Citations (Scopus)

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 language	English
Article number	20131062
Pages (from-to)	N/A
Number of pages	7
Journal	Journal Of The Royal Society Interface
Volume	11
Issue number	94
DOIs	https://doi.org/10.1098/rsif.2013.1062
Publication status	Published - 6 May 2014

Keywords

membrane biophysics
drug transport
lipid hydrolysis
high-performance liquid chromatography
PHASE-TRANSITIONS
PHOSPHOLIPID-BILAYERS
FATTY-ACIDS
PHOSPHATIDYLCHOLINE
LIPOSOMES
TRANSPORT
BINDING

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10.1098/rsif.2013.1062

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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.",

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author = "Duncan Casey and Kalypso Charalambous and Antony Gee and Law, {Robert V.} and Oscar Ces",

year = "2014",

month = may,

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doi = "10.1098/rsif.2013.1062",

language = "English",

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journal = "Journal Of The Royal Society Interface",

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AU - Casey, Duncan

AU - Charalambous, Kalypso

AU - Gee, Antony

AU - Law, Robert V.

AU - Ces, Oscar

PY - 2014/5/6

Y1 - 2014/5/6

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AB - 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.

KW - membrane biophysics

KW - drug transport

KW - lipid hydrolysis

KW - high-performance liquid chromatography

KW - PHASE-TRANSITIONS

KW - PHOSPHOLIPID-BILAYERS

KW - FATTY-ACIDS

KW - PHOSPHATIDYLCHOLINE

KW - LIPOSOMES

KW - TRANSPORT

KW - BINDING

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DO - 10.1098/rsif.2013.1062

M3 - Article

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JO - Journal Of The Royal Society Interface

JF - Journal Of The Royal Society Interface

IS - 94

M1 - 20131062

ER -

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

Abstract

Keywords

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