The Permeability Enhancing Mechanism of DMSO in Ceramide Bilayers Simulated by Molecular Dynamics

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 (> or =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.

Water permeation through stratum corneum lipid bilayers from atomistic simulations

“…The dihedral potentials in the lipid tails were described by the Ryckaert-Bellemans term 26 . At skin conditions the SC lipids do not fully ionize, so, polar groups were assigned partial charges chosen from previous simulations of similar molecules 27,28 . The partial charges along with schematic representations of the lipid molecules are shown in Fig.…”

Ethanol induces the formation of water-permeable defects in model bilayers of skin lipids

“…The united atom force field employed for the CER2 lipids was the same as in our previous work 5 . To summarise, the interaction parameters for the hydrocarbon tails were taken from the force field of Berger 6 , which is parameterised for phospholipids and uses GROMOS87 parameters for headgroups, and specially adapted parameters for lipid tails.…”

A permeability barrier surrounds taste buds in lingual epithelia

“…The aprotic solvent DMSO disrupts membranes through a number of postulated mechanisms, including the induction of water pores within the membrane (37,38) and the introduction of structural defects in the bilayers through interactions with phospholipid acyl chains (52). When applied at sufficiently high concentrations (optimally, 75%), DMSO significantly improved CMFDA penetration into taste buds, whether applied to the slice of lingual tissue (Fig.…”