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

Salminen, Alec T.; Davis, Kelly J.; Felton, Robert P.; Nischal, Nathania; VonTungeln, Linda S.; Beland, Frederick A.; Derr, Kristy; Brown, Paul C.; Ferrer, Marc; Katz, Linda M.; Kleinstreuer, Nicole C.; Leshin, Jonathan; Manga, Prashiela; Sadrieh, Nakissa; Xia, Menghang; Fitzpatrick, Suzanne C.; Camacho, Luísa

doi:10.1016/j.tiv.2023.105630

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

Journal Article · Tue Jun 13 00:00:00 EDT 2023 · Toxicology in Vitro

DOI:https://doi.org/10.1016/j.tiv.2023.105630· OSTI ID:2425757

Salminen, Alec T. ^[1]; Davis, Kelly J. ^[2]; Felton, Robert P. ^[1]; Nischal, Nathania ^[1]; VonTungeln, Linda S. ^[1]; Beland, Frederick A. ^[1]; Derr, Kristy ^[3]; Brown, Paul C. ^[4]; Ferrer, Marc ^[3]; Katz, Linda M. ^[5]; Kleinstreuer, Nicole C. ^[6]; Leshin, Jonathan ^[7]; Manga, Prashiela ^[5]; Sadrieh, Nakissa ^[4]; Xia, Menghang ^[3]; Fitzpatrick, Suzanne C. ^[5]; Camacho, Luísa ^[1]

U.S. Food and Drug Administration, Jefferson, AR (United States)
Toxicologic Pathology Associates, Jefferson, AR (United States)
National Institutes of Health, Rockville, MD (United States)
U.S. Food and Drug Administration, Silver Spring, MD (United States)
U.S. Food and Drug Administration, College Park, MD (United States)
National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)
U.S. Food and Drug Administration, Rockville, MD (United States)

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/cm2) 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. Altogether, 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.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2425757

Alternate ID(s):: OSTI ID: 1999850

Journal Information:: Toxicology in Vitro, Journal Name: Toxicology in Vitro Journal Issue: C Vol. 91; ISSN 0887-2333

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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

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