Effect of l-menthol on the thermotropic behavior of ceramide 2/cholesterol mixtures as a model for the intercellular lipids in stratum corneum.

The major components of the intercellular lipids in the stratum corneum are ceramides (CERs), cholesterol (CHOL) and free fatty acids. To estimate the effects of l-menthol on the intercellular lipids, we elucidated the thermotropic behavior and lateral structure of a CER2/CHOL mixture. This formed a eutectic mixture at molar fraction of CHOL (Xch) = 0.6, as a lamellar structure with a repeat distance of 3.99 nm, and it showed a hexagonal hydrocarbon chain packing conformation at ambient temperature. In thermograms of the CER2/CHOL mixtures, the addition of l-menthol broadened the transition peaks and reduced the enthalpy of transition. The effect of l-menthol on the change in transition temperature of the eutectic mixture at Xch = 0.6 was weaker than for other molar fractions of CHOL. This suggested that the structure of the eutectic mixture was stable to the effects of l-menthol. Furthermore, l-menthol increased the repeat distance of the lamellar structure and inhibited the formation of hexagonal hydrocarbon chain packing. Therefore, l-menthol induced a disturbance of the lateral structure of the eutectic mixture of CER2/CHOL and the phase transition became unclear. These effects of l-menthol could enhance transdermal drug delivery.