Abstract
The permeability barrier of hairless mouse skin has been determined in vitro after exposure of the epidermal surface to volumes of acetone typically used in human in vivo skin penetration studies. It has been shown that the transport of tritiated water (when applied for limited 5-h periods) across hairless mouse skin is not affected by acetone treatments of approximately 15 μl/cm2. Submersion of the membranes between aqueous donor and receptor phases for periods greater than 24 h, however, leads to significant and catastrophic barrier impairment. The acetone dose in the experiments reported is greater than that employed in vivo when the solvent is used to deposit a penetrant on human skin. We suggest, therefore, that acetone-mediated facilitation of percutaneous absorption in humans is unlikely. A further conclusion of this work is that in vitro solvent-deposition penetration experiments using hairless mouse skin should provide reliable transport information for at least 48 h postadministration. Although hairless mouse skin is more permeable than its human counterpart, in vitro measurements using the murine barrier should, therefore, provide useful and relevant guidelines for risk assessment calculations and bioavailability determinations.
| Original language | English |
|---|---|
| Pages (from-to) | 87-91 |
| Number of pages | 5 |
| Journal | Journal Of Investigative Dermatology |
| Volume | 93 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 31 Jul 1989 |
Bibliographical note
Funding Information:The heightened interest in assessing percutaneous transport has led several investigators to use substitutes for human skin. It is sometimes difficult to obtain human tissue in a regular or timely fashion; in addition, the high level of variability associated with cadaver skin [8] has frustrated researchers and has directed them to consider alternatives. Of the various models that have been studied the skin of the hairless mouse is probably the mostropular. There is no doubt that this tissue has enabled a number 0 key studies that have greatly increased our understanding of the skin permeation process. For example, it has allowed fundamental research into structure - penetration relationships [9 -12], concurrent transport and metabolism [13 - 16), and the effects of skin damage on barrier Manuscript received June 21 , 1988; accepted for publication January 6, 1989. This work was supported by National Institutes of Health grants GM-33395 and HD-23010 and by the U.S. Environmental Protection Agency through cooperative agreement, CR-812474. Reprint requests to: Dr. R. H. Guy, School of Pharmacy, University of California, San Francisco, CA 94143-0446.
Funding
The heightened interest in assessing percutaneous transport has led several investigators to use substitutes for human skin. It is sometimes difficult to obtain human tissue in a regular or timely fashion; in addition, the high level of variability associated with cadaver skin [8] has frustrated researchers and has directed them to consider alternatives. Of the various models that have been studied the skin of the hairless mouse is probably the mostropular. There is no doubt that this tissue has enabled a number 0 key studies that have greatly increased our understanding of the skin permeation process. For example, it has allowed fundamental research into structure - penetration relationships [9 -12], concurrent transport and metabolism [13 - 16), and the effects of skin damage on barrier Manuscript received June 21 , 1988; accepted for publication January 6, 1989. This work was supported by National Institutes of Health grants GM-33395 and HD-23010 and by the U.S. Environmental Protection Agency through cooperative agreement, CR-812474. Reprint requests to: Dr. R. H. Guy, School of Pharmacy, University of California, San Francisco, CA 94143-0446.
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Dermatology
- Cell Biology