Limitations of hairless mouse skin as a model for in vitro permeation studies through human skin: hydration damage.

Hairless mouse skin currently provides a popular model membrane for studies in human percutaneous absorption. Although some similarities between the two skin types have been demonstrated, the effects of prolonged hydration on hairless mouse skin have not previously been rigorously examined. We have measured in vitro the effects of hydration at 31 degrees C on the permeabilities of hairless mouse skin and human abdominal and scalp skin to a model polar compound (water) and a lipid material (hexanol). The permeability of hairless mouse skin rose dramatically, especially to water (fiftyfold increase), whereas the human skin was more stable. We also compared the effects of stripping the stratum corneum with the effects of 8-d hydration for hairless mouse and human abdominal skin. Hydration of hairless mouse skin was as effective as tape-stripping in eliminating the stratum corneum barrier, whereas stripping human skin was far more damaging than hydration, suggesting that prolonged hydration mechanically disrupted mouse skin but not human skin. Histological examination of fresh and hydrated tissues confirmed this suggestion. We therefore recommend that hairless mouse skin is not used as a model for human tissue during in vitro permeation studies under conditions of long-term hydration, i.e., greater than three days.