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.

Potential of Stratum Corneum Lipid Liposomes for Screening of Chemical Skin Penetration Enhancers

“…34,35) However, the interactions of these CPEs with SC lipids was mainly on the polar head region. 34,36,37) Therefore, low fluidity in the hydrophobic chain of SCLL lipids was observed in our study.…”

Effect of different alcohols on stratum corneum kallikrein 5 and phospholipase A2 together with epidermal keratinocytes and skin irritation

“…Moghadem et al [21] reported that ethanol produces very little change in the small-and wide-angle diffraction patterns of SC lipids. However, examining hairless mouse skin, Horita et al [22] reported that ethanol modified the short but not the long periodicity phase of SC lipids. Changes to keratin structure have also been reported with increasing concentrations of ethanol.…”

Effect of terpinyl acetate on the percutaneous absorption of caffeine in rats

“…[9] The results revealed that ethanol modifies both the short lamellar structures, including the aqueous layer in intercellular lipids, and the structure of keratin fibrils in corneocytes, which can penetrate hydrophilic compounds such as caffeine.…”

“…In ceramide, fatty acids are linked with sphingosine back bone, and a 2-amino, 1, 3-diol head of sphingosine can hinder any substance with a hydrophilic residue from penetrating the skin by means of hydrogen bonding. [9] TA might disrupt the hydrogen bond between caffeine and ceramide, and consequently, percutaneous caffeine absorption could be significantly increased.…”

“…Histamine regulates the expression of nerve growth factor (NGF) and semaphoring 3A (Sema3A), associated with nerve fibre elongation (s1). [9] This study uses surfactant-treated ICR mice, HDCknockout mice and the wild-type mice (s2) to investigate the role of epidermal histamine in nerve fibre elongation.…”