TY - JOUR

T1 - The permeability enhancing mechanism of DMSO in ceramide Bilayers simulated by molecular dynamics

AU - Notman, Rebecca

AU - den Otter, Wouter K.

AU - Noro, Massimo G.

AU - Briels, W. J.

AU - Anwar, Jamshed

PY - 2007/9

Y1 - 2007/9

N2 - 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.

AB - 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.

KW - PHOSPHOLIPID-BILAYERS

KW - PHASE-BEHAVIOR

KW - TRANSFORM INFRARED-SPECTROSCOPY

KW - X-RAY-DIFFRACTION

KW - HYDRATION

KW - DIMETHYL-SULFOXIDE

KW - PENETRATION ENHANCERS

KW - DIMETHYLSULFOXIDE

KW - HUMAN STRATUM-CORNEUM

KW - TEMPERATURE

U2 - 10.1529/biophysj.107.104703

DO - 10.1529/biophysj.107.104703

M3 - Journal article

VL - 93

SP - 2056

EP - 2068

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 6

ER -