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Cited by 25Advancements in Transdermal Drug DeliveryContact Dermatitis and AllergiesAnimal testing and alternatives

Parallel evaluation of alternative skin barrier models and excised human skin for dermal absorption studies in vitro

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Salminen, Alec T., Davis, Kelly J., Felton, Robert P., Nischal, Nathania, VonTungeln, Linda S., Beland, Frederick A., Derr, Kristy, Brown, Paul C. +9 more·2023·Toxicology in Vitro
DOI 10.1016/j.tiv.2023.105630PMC PMC10527924
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Abstract

Skin permeation is a primary consideration in the safety assessment of cosmetic ingredients, topical drugs, and human users handling veterinary medicinal products. While excised human skin (EHS) remains the 'gold standard' for in vitro permeation testing (IVPT) studies, unreliable supply and high cost motivate the search for alternative skin barrier models. In this study, a standardized dermal absorption testing protocol was developed to evaluate the suitability of alternative skin barrier models to predict skin absorption in humans. Under this protocol, side-by-side assessments of a commercially available reconstructed human epidermis (RhE) model (EpiDerm-200-X, MatTek), a synthetic barrier membrane (Strat-M, Sigma-Aldrich), and EHS were performed. The skin barrier models were mounted on Franz diffusion cells and the permeation of caffeine, salicylic acid, and testosterone was quantified. Transepidermal water loss (TEWL) and histology of the biological models were also compared. EpiDerm-200-X exhibited native human epidermis-like morphology, including a characteristic stratum corneum, but had an elevated TEWL as compared to EHS. The mean 6 h cumulative permeation of a finite dose (6 nmol/cm 2) of caffeine and testosterone was highest in EpiDerm-200-X, followed by EHS and Strat-M. Salicylic acid permeated most in EHS, followed by EpiDerm-200-X and Strat-M. Overall, evaluating novel alternative skin barrier models in the manner outlined herein has the potential to reduce the time from basic science discovery to regulatory impact.

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  • HEE models offer dependable substitutes for in vitro permeation testing studies.

    “For instance, the HEE models offer dependable substitutes for in vitro permeation testing studies, a domain historically plagued by the unpredictable availability and exorbitant cost associated with excised human skin [26].”

    From Diversity of human skin three-dimensional organotypic cultures (2024) · cites this paper as [26]

    The Introduction (§2) says the tested alternative models differ greatly in their ability to model permeation through excised human skin. The Discussion (§5) concludes that alternative models require continued improvement before they can predict permeation across human skin, contrary to calling them dependable substitutes. The paper does support the separate point that excised human skin has limited availability and high cost. (LLM, conf=0.88)

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Research works printed but not linked: 9

  1. [3]3. Gilaberte Y, Prieto-Torres L, Pastushenko I, and Juarranz Á, Anatomy and function of the skin, in Nanoscience in Dermatology, Hamblin MR, Avci P, and Prow TW, Editors. 2016, Academic Press: Boston. p. 1-14.
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Authors
Salminen, A. T., Davis, K. J., Felton, R. P., Nischal, N., VonTungeln, L. S., Beland, F. A., Derr, K., Brown, P. C., Ferrer, M., Katz, L. M., Kleinstreuer, N. C., Leshin, J., Manga, P., Sadrieh, N., Xia, M., Fitzpatrick, S. C., & Camacho, L.
Affiliations
  • National Center for Toxicological Research (US)
  • National Center for Advancing Translational Sciences (US)
  • United States Food and Drug Administration (US)
  • Center for Food Safety and Applied Nutrition (US)
  • National Institutes of Health (US)
  • Center for Veterinary Medicine (US)
Corresponding author
Camacho, Luísa
ORCID
Venue
Toxicology in Vitro
Publisher
Elsevier BV
Published
2023-09
Volume
91
Pages
105630
ISSN
0887-2333 (ISSN-L)
DOI
10.1016/j.tiv.2023.105630
PMC
PMC10527924
OpenAlex
W4380358984
Cited by
25
References
3
Citations by year
2026: 10 · 2025: 8 · 2024: 6 · 2023: 1
FWCI
2.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Toxicology in Vitro (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • Oak Ridge Institute for Science and Education
  • U.S. Department of Energy
  • U.S. Food and Drug Administration
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
  • Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
  • Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Keywords
excised human skin, reconstructed human epidermis, percutaneous absorption, skin permeation, caffeine, salicylic acid, testosterone, transepidermal water loss, stratum corneum, Franz diffusion cell, cosmetic ingredients, topical drugs
MeSH terms
Caffeine, Epidermis, Humans, Skin, Skin Absorption, Testosterone, Water, Salicylic Acid

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