Garcia, N., O. Doucet, M. Bayer, L. Zastro, and J.Marty.  Characterisation of the Barrier Function Offered by a Three-Dimensional Skin Culture Model Through Percutaneous Absorption, Transepidermal Water Loss Measurements and Impedance Measurements.  ATLA 27:  308.  1999.

 

Previous studies have clearly underlined the interest of three-dimensional skin cultures in the field of cell pharmacotoxicology.  However, so far, few studies have dealt with the use of these organotypic cultures, as screening models, to achieve percutaneous absorption experiments.  The aim of this work was to characterize the barrier function offered by a commercially available reconstituted epidermis (Rep) by using percutaneous absorption analysis and non-invasive measurements.  The magnitude of the barrier function of Rep was first assessed and compared to normal human skin (NHS) through transepidermal water loss measurements (TEWL).  Results obtained demonstrated that the TEWL of Rep cultures (13 ± 3 g/m2/hour) was only slightly higher than that measured under the same environmental conditions, in vivo, in human volunteers, or ex vivo through excised human skin mounted on Franz’s diffusion cells.  The surface hydration state of Rep cultures, measured under the same experimental conditions, through impedance measurements was similarly slightly higher than the one measured either in vivo or ex vivo, in human skin.  Skin penetration experiments, performed by using 12 chemicals, indicated a linear correlation (R=0.93, p < 0.001) between the maximal flux (ug/hour/cm2) measured, in vitro, through normal human skin and Rep cultures.  Whatever the hydrophobicity of the chemical applied, Rep were globally 10-fold more permeable than NHS biopsies.  Interestingly, some alterations in the barrier function of excised human skin, induced by applying (as pre-treatment) organic solvents might be reproduced, in this Rep model, for TEWL and percutaneous penetration of fast diffusing chemicals, such as caffeine.