Comparison of Several Reconstructed Cultured Human Skin Models by Microscopic Observation: Their Usefulness as an Alternative Membrane for Skin in Drug Permeation Experiments

摘要

Several reconstructed cultured human skin models (RSMs) are already utilized as membrane alternatives to human and animal skin in skin corrosive/irritation tests. They are also utilized in skin permeation experiments from the viewpoint of animal welfare; however, different permeation profiles of chemicals were found between RSMs and excised human or animal skin. RSMs and excised human skin were morphologically evaluated by a light microscope and a transmission electron microscope. In the results, themicromorphology of all RSMs differed from that of human skin. In particular, the lamellar layer between corneocytes in RSMs was much narrower than that in the human stratum corneum. The lamella layer affects not only the diffusion and partition properties of chemical compounds in RSMs but also the concentration-distance profile of chemicals in the models. Furthermore, esterase distribution in RSMs was different to that in human skin. This difference would certainly affect the permeation of both parentester compounds and their metabolites through RSMs. Evaluation of the morphological and enzymatic differences between RSMs and human skin would be helpful to understand the differences in the chemical permeation profiles between RSMs and human skin.