期刊
BIOCHIMIE
卷 94, 期 1, 页码 2-10出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2011.07.029
关键词
Lipids; Curvature stress; Liposome; Permeability; Free fatty acids; Lysolipids; Doxorubicin; Drug delivery
资金
- Danish Cancer Society
- Danish Research Council
- Race against Breast Cancer
- Danish Centre for Translational Breast Cancer Research
- Centre of Excellence: Sino-Danish Breast Cancer Research Centre
- Lundbeck Research Center NanoCAN
- National Danish Graduate School of Molecular Biophysics
- Danish National Research Foundation
Molecular shape and its impact on bilayer curvature stress are powerful concepts for describing the effects of lipids and fatty acids on fundamental membrane properties, such as passive permeability and derived properties like drug transport across liposomal membranes. We illustrate these relationships by studying the effects of fatty acids and lysolipids on the permeation of a potent anti-cancer drug, doxorubicin, across the bilayer of a liposome in which the drug is encapsulated. Using a simple fluorescence assay, we have systematically studied the passive permeation of doxorubicin across liposomal membranes in different lipid phases: the solid-ordered phase (DPPC bilayers), the liquid-disordered phase (POPC lipid bilayers), and the liquid-ordered phase induced by high levels of cholesterol (DOPC + cholesterol lipid bilayers). The effect of different free fatty acids (FA) and lysolipids (LL), separately and in combination, on permeability was assessed to elucidate the possible mechanism of phospholipase A(2)-triggered release in cancer tissue of liposomal doxorubicin formulations. In all cases, FAs applied separately lead to significant enhancement of permeability, most pronounced in liquid-disordered bilayers and less pronounced in solid and solid-ordered bilayers. LLs applied separately had only a marginal effect on permeability. FA and LL applied in combination lead to a synergistic enhancement of permeability in solid bilayers, whereas in liquid-disordered bilayers, the combined effect suppressed the otherwise strong permeability enhancement due to the FAs. (C) 2011 Elsevier Masson SAS. All rights reserved.
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