The permeability enhancing mechanism of DMSO in ceramide bilayers simulated by molecular dynamics
Notman, Rebecca, Denotter, W., Noro, Massimo, 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 0006-3495Full text not available from this repository.
Official URL: http://dx.doi.org/10.1529/biophysj.107.104703
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|
|Official Date:||September 2007|
|Page Range:||pp. 2056-2068|
|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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