l-Menthol increases drug partitioning on the surface of skin, diffusion of drugs in the skin, and lipid fluidity in the stratum corneum and alters the rigidly arranged lipid structure of intercellular lipids. However, l-menthol is a solid at room temperature, and it is difficult to determine the effects of l-menthol alone. In this study, we vaporized l-menthol in order to avoid the effects of solvents. The vaporized l-menthol was applied to the stratum corneum or lipid models comprising composed of ceramides (CER) [EOS], the longest lipid acyl chain of the ceramides in the stratum corneum lipids that is associated with the barrier function of the skin; CER [NS], the shorter lipid acyl chain of the ceramides, and the most components in the stratum corneum of the intercellular lipids that is associated with water retention in the intercellular lipid structure of the stratum corneum; cholesterol; and palmitic acid. Synchrotron X-ray diffraction, differential scanning calorimetry, and attenuated total reflection Fourier transform infrared spectroscopy analyses revealed that the lipid models were composed of hexagonal packing and orthorhombic packing structures of different lamellar periods. Taken together, our results revealed that l-menthol strongly affected the lipid model composed of CER [EOS]. Therefore, l-menthol facilitated the permeation of drugs through the skin by liquid crystallization of the longer lamellar structure. Importantly, these simple lipid models are useful for investigating microstructure of the intercellular lipids in the stratum corneum.Key words intercellular lipid; stratum corneum; synchrotron X-ray diffraction; lipid model; vaporized lmenthol The stratum corneum, as the outer skin layer, plays an important role in biological defense mechanisms, such as protection from bacteria and foreign matter intrusion and maintenance of moisture. The rigid arrangement of intercellular lipids, composed of ceramides (CERs), cholesterol (CHOL), free fatty acids (FFAs), and their derivatives, plays a major role in the barrier function of the tissue.1-3) Recent reports have shown that CER [EOS] is associated with the barrier function of the skin, while CER [NS] is related to water retention in the intercellular lipid structure of the stratum corneum. 4,5) CERs, CHOL, and FFAs, components of intercellular lipids, form the lipid bilayer, in which the hydrophobic groups face each other.
6)Small-angle X-ray diffraction has shown that there are two types of lamellar structures: a short lamellar structure with a repeat distance of about 6 nm, and a long lamellar structure with a repeat distance of about 13 nm.7-9) The observation of hydrocarbon chain packing by wide-angle X-ray diffraction has reveal hexagonal packing with a lattice distance of about 0.42 nm and orthorhombic packing with lattice distances of about 0.42 and 0.37 nm. [9][10][11] Although the majority of water is held in the stratum corneum of corneocytes, a portion of the water is taken into the intercellular lipid structure of the stratum corneum....