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Limitations of hairless mouse skin as a model for in vitro permeation studies through human skin: hydration damage
Abstract:
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.
Insights
Prolonged hydration significantly increases hairless mouse skin permeability, unlike human skin. This study advises against using hairless mouse skin for in vitro permeation studies under long-term hydration conditions.
Area of Science:
- Dermatology
- Pharmacokinetics
- Biomaterials Science
Background:
- Hairless mouse skin is a common model for human percutaneous absorption studies.
- Previous research has not rigorously examined the effects of prolonged hydration on this model.
- Understanding skin barrier function under various conditions is crucial for accurate absorption studies.
Purpose of the Study:
- To investigate the impact of prolonged hydration on the permeability of hairless mouse skin compared to human skin.
- To assess the mechanical effects of hydration on the stratum corneum barrier in both skin types.
- To determine the suitability of hairless mouse skin as a model for human skin under long-term hydration.
Main Methods:
- In vitro measurement of water and hexanol permeability across hairless mouse, human abdominal, and scalp skin.
- Comparison of the effects of 8-day hydration versus tape-stripping on stratum corneum integrity.
- Histological examination of fresh and hydrated skin tissues.
Main Results:
- Hairless mouse skin permeability increased dramatically (50-fold for water) with hydration, while human skin remained more stable.
- Hydration disrupted the stratum corneum barrier in mouse skin as effectively as tape-stripping.
- Tape-stripping damaged human skin more than hydration, indicating mechanical disruption in mouse skin but not human skin.
Conclusions:
- Prolonged hydration (>3 days) mechanically disrupts hairless mouse skin, compromising its barrier function.
- Hairless mouse skin is not a suitable model for human skin in in vitro permeation studies involving long-term hydration.
- Results suggest significant differences in skin hydration response between mouse and human tissues.