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

Satoshi Kano1, Hiroaki Todo1, Katsunori Furui1, Kenichi Sugie1, Yoshihiro Tokudome1, Fumie Hashimoto1, Hajime Kojima3, Kenji Sugibayashi1,2

1Faculty of Pharmaceutical Sciences and 2Life Science Research Center, Josai University, Saitama, Japan
3National Institute of Health Sciences, Tokyo, Japan

AATEX 16(2):51-58, 2011

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, the micromorphology 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 parent ester 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.

key words: reconstructed cultured human skin model, skin permeation, skin morphology, lamella layer


(AATEX: Altern. Animal Test. EXperiment.: Alternatives to Animal Testing and EXperimentation)