Characterization and ex vivo evaluation of excised skin samples as substitutes for human dermal barrier in pharmaceutical and dermatological studies

Skin Res Technol. 2022 Sep;28(5):664-676. doi: 10.1111/srt.13165. Epub 2022 Jun 21.

Abstract

Background: Excised animal and human skins are frequently used in permeability testing in pharmaceutical research. Several factors exist that may have influence on the results. In the current study some of the skin parameters that may affect drug permeability were analysed for human, mouse, rat and pig skin.

Materials and methods: Classic biophysical skin parameters were measured (e.g. pH, hydration, permittivity, transepidermal water loss). Physiological characteristics of the skins were also analysed by confocal Raman spectroscopy, scanning electron microscopy and two-photon microscopy.

Results: Based on biophysical testing, skin barrier function was damaged in psoriatic mouse skin and in marketed pig skin. Hydration and pH values were similar among the species, but freezing and thawing reduced the water content of the skins and shifted the surface pH to acidic. Aging reduced hydration and permittivity, resulting in impaired barrier function. Mechanical sensitization used in permeability studies resulted in proportional thinning of dead epidermis.

Discussion: Results indicate that depending on the scientific question it should be considered whether fresh or frozen tissue is used, and for certain purposes rodent skins are well usable. The structure of the skin tissue (ceramide, cholesterol, keratin, natural moisturizing factor or urea) is similar in rats and mice, but due to the higher skin thickness the lipid distribution is different in porcine skin. Psoriasis led to irregular chemical composition of the skin.

Conclusion: A comprehensive evaluation of skin samples of four species was performed. The biophysical and microscopic observations should be considered when selecting drug penetration models and experimental conditions.

Keywords: TEWL; aging; confocal Raman spectroscopy; dermal barrier; excised skins; freezing/thawing; hydration; scanning electron microscopy; tape stripping; two-photon microscopy.

MeSH terms

  • Animals
  • Ceramides / metabolism
  • Epidermis
  • Humans
  • Keratins / metabolism
  • Mice
  • Pharmaceutical Preparations / metabolism
  • Rats
  • Skin* / metabolism
  • Swine
  • Urea / metabolism
  • Water / metabolism
  • Water Loss, Insensible* / physiology

Substances

  • Ceramides
  • Pharmaceutical Preparations
  • Water
  • Keratins
  • Urea