title: Molecular mechanisms of action of different concentrations of ethanol in water on ordered structures of intercellular lipids and soft keratin in the stratum corneum.
abstract: Ethanol (EtOH) is one of the bases in topically applied medicines that promote the skin permeation of drugs. Although the effects of EtOH have been attributed to structural modifications in the stratum corneum, the underlying mechanisms, especially the influence of different concentrations of EtOH, have not been examined extensively. Structural modifications in the stratum corneum of hairless mouse due to the application of EtOH/water mixture were herein investigated at the molecular level using synchrotron X-ray diffraction. The results revealed that all EtOH concentrations examined greatly modified the short lamellar structures containing the aqueous layer in intercellular lipids and the structure of keratin fibrils in corneocytes, which can take up hydrophilic compounds. However, the long lamellar and the hydrocarbon-chain packing structures were unaffected by EtOH. Changes to the short lamellar structures were not proportional to the concentration of EtOH. However, the keratin fibril structures changed gradually with increasing EtOH concentration. The X-ray diffraction experiments enabled the effects of different EtOH concentrations on the morphology of the stratum corneum to be assessed by using a number of experimental samples to avoid variations due to individual differences. The results indicated that alterations to the short lamellar structures appeared to be related to the skin permeability of drugs with the application of EtOH/water mixture, and monotonous structural changes in the keratin fibrils with an increase in EtOH concentration may contribute to this permeation as supplement. These results will be useful for the development of new drug formulations containing EtOH.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan; Research Laboratories, Ikeda Mohando Co., Ltd., 16 Jinden, Kamiichi, Nakaniikawa, Toyama 930-0394, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Horita
authors.affiliation: Department of Research, Nagoya Industrial Science Research Institute, 1-13 Yotsuyadori, Chikusa-ku, Nagoya 464-0819, Japan; Aichi Synchrotron Radiation Center, Aichi Science & Technology Foundation, 250-3 Minamiyamaguchi-cho, Seto, Aichi 489-0965, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hatta
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yoshimoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kitao
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Todo
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan; Life Science Research Center, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: sugib@josai.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugibayashi
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D007633:Keratins / Q000737:chemistry / Q000378:metabolism*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008812:Mice, Hairless; D010539:Permeability; D011487:Protein Conformation; D053838:Scattering, Small Angle; D012867:Skin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D017356:Synchrotrons; D014867:Water / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D008563:Membrane Lipids; D014867:Water; D000431:Ethanol; D007633:Keratins
keywords: Corneocyte; Ethanol; Hairless mouse; Intercellular lipids; Stratum corneum; X-ray diffraction