Notman, Rebecca, Denotter, W., Noro, Massimo, 1968-, Briels, W. J. and Anwar, Jamshed. (2007) The permeability enhancing mechanism of DMSO in ceramide bilayers simulated by molecular dynamics. Biophysical Journal, Vol.93 (No.6). pp. 2056-2068. ISSN 0006-3495

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Abstract

The lipids of the topmost layer of the skin, the stratum corneum, represent the primary barrier to molecules penetrating the skin. One approach to overcoming this barrier for the purpose of delivery of active molecules into or via the skin is to employ chemical permeability enhancers, such as dimethylsulfoxide ( DMSO). How these molecules exert their effect at the molecular level is not understood. We have investigated the interaction of DMSO with gel-phase bilayers of ceramide 2, the predominant lipid in the stratum corneum, by means of molecular dynamics simulations. The simulations satisfactorily reproduce the phase behavior and the known structural parameters of ceramide 2 bilayers in water. The effect of DMSO on the gel-phase bilayers was investigated at various concentrations over the range 0.0-0.6 mol fraction DMSO. The DMSO molecules accumulate in the headgroup region and weaken the lateral forces between the ceramides. At high concentrations of DMSO (>= 0.4 mol fraction), the ceramide bilayers undergo a phase transition from the gel phase to the liquid crystalline phase. The liquid-crystalline phase of ceramides is expected to be markedly more permeable to solutes than the gel phase. The results are consistent with the experimental evidence that high concentrations of DMSO fluidize the stratum corneum lipids and enhance permeability.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	Dimethyl sulfoxide, Ceramides -- Permeability, Bilayer lipid membranes -- Permeability, Molecular dynamics -- Computer simulation
Journal or Publication Title:	Biophysical Journal
Publisher:	Biophysical Society
ISSN:	0006-3495
Date:	September 2007
Volume:	Vol.93
Number:	No.6
Page Range:	pp. 2056-2068
Identification Number:	10.1529/biophysj.107.104703
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Engineering and Physical Sciences Research Council (EPSRC), Unilever (Firm), EU Network of Excellence SoftComp
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URI:	http://wrap.warwick.ac.uk/id/eprint/40620

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