Characterization, Barrier Function, and Drug Metabolism of an In Vitro Skin Model

To evaluate the epidermal barrier function of in vitro reconstructed epidermis, we measured the penetration of estradiol and water across human keratinocytes cultured in defined medium (DM), in the presence of proliferative fibroblasts (pF) or conditioned medium derived from pF, at the air-liquid interface on synthetic porous membrane, noncoated or coated with laminin, fibronectin, type I collagen or type IV collagen. Ultrastructural analysis showed a well-developed stratum corneum whatever the culture conditions. The permeability of reconstructed epidermis in DM on a noncoated porous membrane was 5- to 10-fold higher than human native epidermis, with both tracers. No significant change in barrier function was observed whatever the culture conditions.

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 74%

Barrier Function of Reconstructed Epidermis at the Air-Liquid Interface: Influence of Dermal Cells and Extracellular Components

Robert

Dusser

et al. 1997

“…The success in the clinic has led scientists to believe that these models could be considered as a feasible alternative to replace the traditional skin models in toxicological and pharmacological studies in vitro. Recently these models have been used for shortterm cytotoxicity assays [7] and skin metabolism studies [8] . However, their use in vitro is still limited due to a deficient barrier function.…”

Section: Introductionmentioning

confidence: 99%

Improvement of Epidermal Barrier Properties in Cultured Skin Substitutes after Grafting onto Athymic Mice

Barai¹,

Supp

Kasting³

et al. 2006

Barrier function in cultured skin substitutes (CSS) prepared from human cell sources was measured by noninvasive (surface hydration, transepidermal water loss) and invasive methods (water permeation, niacinamide flux) before and after grafting onto athymic mice. In vitro measurements were made on days 7 and 14. Although three of the four measures of barrier function improved markedly from day 7 to 14, the values obtained were still far from those obtained with native human skin controls. Additional CSS were grafted onto athymic mice on day 14, and skin was harvested 2 and 6 weeks after grafting. Grafting brought about a substantial decrease in all measurements by 2 weeks and almost complete normalization of barrier function after 6 weeks. The most sensitive measure of this recovery was niacinamide permeability, which decreased from (280 ± 40) × 10^–4 cm/h in vitro to (17 ± 30) × 10^–4 cm/h 2 weeks after grafting and (5 ± 2) × 10^–4 cm/h 6 weeks after grafting, versus control values of (2 ± 2) × 10^–4 cm/h in human cadaver skin and (0.6 ± 0.4) × 10^–4 cm/h in human epidermal membrane prepared from freshly excised breast skin. These results demonstrate the reformation of epidermal barrier function after transplantation and provide insights for the development of a functional epidermal barrier in CSS in vitro.

“…Although human skin models were shown to be more permeable than human skin ex vivo, they seemed to correctly predict the permeability rank order of compounds with different physicochemical properties when they were applied in simple vehicles at infinite doses [4][5][6][7]. However, only few studies have been reported on human skin models dealing with vehicle effects on percutaneous penetration [4,[8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Cutaneous Bioavailability of Cosmetic Preparations Containing Caffeine or α-Tocopherol Applied on Human Skin Models or Human Skin ex vivo at Finite Doses

Dreher

Fouchard²,

Patouillet³

et al. 2002

The use of human skin models for performing cutaneous bioavailability studies has been little investigated. For instance, only few studies have been reported on human skin models dealing with vehicle effects on percutaneous penetration. The present study aimed at evaluating the influence on caffeine’s and α-tocopherol’s cutaneous bioavailability of cosmetic vehicles such as a water-in-oil emulsion, an oil-in-water emulsion, a liposome dispersion and a hydrogel applied at finite dose using the reconstructed human skin models EpiDerm^® and Episkin^®. The results were compared with those obtained in human skin ex vivo using similar experimental conditions. It was demonstrated that the rank order of solute permeability could be correctly predicted when the preparation was applied at a finite dose in human skin models, at least when solutes with far different physicochemical properties such as caffeine and α-tocopherol were used. If only slight effects of cosmetic vehicle on skin bioavailability were observed in human skin ex vivo, they were less predictable using skin models. Especially, alcohol-containing vehicles seemed to behave differently in EpiDerm as well as in Episkin than on human skin ex vivo. Stratum corneum intercellular lipid composition and organization of human skin models differ to some extent from that of human stratum corneum ex vivo, which contributes to less pronounced barrier properties, together with the increased hydration of the outermost stratum corneum layers of the models. These features, as well as still unknown factors, may explain the differences observed in vehicle effects in human skin ex vivo versus human skin models.