Evaluation of a human bio-engineered skin equivalent for drug permeation studies.
OBJECTIVE
To test the barrier function of a bio-engineered human skin (BHS) using three model drugs (caffeine, hydrocortisone, and tamoxifen) in vitro. To investigate the lipid composition and microscopic structure of the BHS.


METHODS
The human skin substitute was composed of both epidermal and dermal layers, the latter having a bovine collagen matrix. The permeability of the BHS to three model drugs was compared to that obtained in other percutaneous testing models (human cadaver skin, hairless mouse skin, and EpiDerm). Lipid analysis of the BHS was performed by high performance thin layered chromatography. Histological evaluation of the BHS was performed using routine H&E staining.


RESULTS
The BHS mimicked human skin in terms of lipid composition, gross ultrastructure, and the formation of a stratum corneum. However, the permeability of the BHS to caffeine, hydrocortisone, and tamoxifen was 3-4 fold higher than that of human cadaver skin.


CONCLUSIONS
In summary, the results indicate that the BHS may be an acceptable in vitro model for drug permeability testing.
Asbill
C
C
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South Carolina 29208, USA.
Kim
N
N
El-Kattan
A
A
Creek
K
K
Wertz
P
P
Michniak
B
B
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics; D002110:Caffeine / Q000493:pharmacokinetics*; D002273:Carcinogens / Q000493:pharmacokinetics; D002417:Cattle; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000493:pharmacokinetics*; D008297:Male; D008563:Membrane Lipids / Q000737:chemistry*; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000493:pharmacokinetics; D012869:Skin Absorption; D017768:Skin, Artificial; D013629:Tamoxifen / Q000493:pharmacokinetics*
D000893:Anti-Inflammatory Agents; D002273:Carcinogens; D008563:Membrane Lipids; D010726:Phosphodiesterase Inhibitors; D013629:Tamoxifen; D002110:Caffeine; D006854:Hydrocortisone