title: A custom tailored model to investigate skin penetration in porcine skin and its comparison with human skin.
abstract: Reliable models for the determination of skin penetration and permeation are important for the development of new drugs and formulations. The intention of our study was to develop a skin penetration model which (1) is viable and well supplied with nutrients during the period of the experiment (2) is mimicking human skin as far as possible, but still is independent from the problems of supply and heterogeneity, (3) can give information about the penetration into different compartments of the skin and (4) considers specific inter-individual differences in skin thickness. In addition, it should be quick and inexpensive (5) and without ethical implications (6). Using a chemically divers set of four topically approved active pharmaceutical ingredients (APIs), namely diclofenac, metronidazole, tazarotene, and terbinafine, we demonstrated that the model allows reliable determination of drug concentrations in different layers of the viable epidermis and dermis. For APIs susceptible for skin metabolism, the extent of metabolic transformation in epidermis and dermis can be monitored. Furthermore, a high degree of accordance in the ability for discrimination of skin concentrations of the substances in different layers was found in models derived from porcine and human skin. Viability, proliferation, differentiation and markers for skin barrier function were surveyed in the model. This model, which we call 'Hamburg model of skin penetration' is particularly suited to support a rational ranking and selection of dermatological formulations within drug development projects.
authors: Almirall Hermal, R&D Dermatology, Scholtzstr. 3, 21465 Reinbek, Germany.
authors: Michael E
authors: ME
authors: Herbig
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Pia
authors: P
authors: Houdek
authors: Almirall Hermal, R&D Dermatology, Scholtzstr. 3, 21465 Reinbek, Germany.
authors: Sascha
authors: S
authors: Gorissen
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Michaela
authors: M
authors: Zorn-Kruppa
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Ewa
authors: E
authors: Wladykowski
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Thomas
authors: T
authors: Volksdorf
authors: Agaplesion Diakonieklinikum Hamburg gemeinnützige GmbH, Hamburg, Germany.
authors: Stephan
authors: S
authors: Grzybowski
authors: Agaplesion Diakonieklinikum Hamburg gemeinnützige GmbH, Hamburg, Germany.
authors: Georgios
authors: G
authors: Kolios
authors: Almirall Hermal, R&D Dermatology, Scholtzstr. 3, 21465 Reinbek, Germany.
authors: Christoph
authors: C
authors: Willers
authors: Almirall Hermal, R&D Dermatology, Scholtzstr. 3, 21465 Reinbek, Germany.
authors: Henning
authors: H
authors: Mallwitz
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Ingrid
authors: I
authors: Moll
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address: brandner@uke.de.
authors: Johanna M
authors: JM
authors: Brandner
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D005260:Female; D006801:Humans; D009281:Naphthalenes / Q000008:administration & dosage / Q000378:metabolism*; D009924:Organ Culture Techniques; D012867:Skin / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology*; D013045:Species Specificity; D013552:Swine; D000077291:Terbinafine
chemical_list: D009281:Naphthalenes; D000077291:Terbinafine
keywords: Cutaneous absorption; Dermal penetration; Diclofenac; Differentiation; Human skin; Porcine skin; Skin model; Terbinafine; Tight junctions; Viability