Skip to main content
Log in

Evaluation of a Human Bio-Engineered Skin Equivalent for Drug Permeation Studies

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. 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 chromatrography. Histological evalulation 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. R. L. Bronaugh and H. I. Maibach. In Vitro Percutaneous Absorption: Principles, Fundamentals and Applications, Boca Raton, Fl, CRC Press (1991).

    Google Scholar 

  2. R. Panchagnula, K. Stemmer, and W. A. Ritschel. Animal models for transdermal drug delivery. Methods Find Exp. Clin. Pharmacol. 19:335–341 (1997).

    Google Scholar 

  3. M. Ponec, M. Haverkort, Y. L. Soei, J. Kempenaar, and H. Bodde. Use of human keratinocyte and fibroblast cultures for toxicity studies of topically applied compounds. J. Pharm. Sci. 79:312–316 (1990).

    Google Scholar 

  4. D. A. Godwin, B. B. Michniak, and K. E. Creek. Evaluation of transdermal penetration enhancers using a novel skin alternative. J. Pharm. Sci. 86: 1001–1005 (1997).

    Google Scholar 

  5. I. V. Yannas, J. F. Burke, M. Warpehoski, P. Stasikelis, E. M. Skrabut, and D. P. Orgill. Design principles and preliminary clincial performance of an artificial skin. In Biomaterials: Interfacial Phenomena and Applications. 1982, pp. 476–481.

  6. J. F. Morgan and M. L. Yarmush. Bioengineered skin substitutes. Science & Medicine. 6–15 (1997).

  7. M. Muhart, S. McFalls, R. Kirsner, F. Kerdel, and W. H. Eaglstein. Bioengineered skin [letter]. Lancet. 350:1142 (1997).

    Google Scholar 

  8. T. J. Phillips. New skin for old: Developments in biological skin substitutes [editorial; comment]. Arch. Dermatol. 134:344–349 (1998).

    Google Scholar 

  9. J. F. Trent, R. S. Kirsner. Tissue engineered skin: Apligraf, a bilayered living skin equivalent. Int. J. Clin. Pract. 52:408–413 (1998).

    Google Scholar 

  10. J. G. Rheinwald and H. Green. Serial cultivation of strains of human epidermal keratinocytes. The formation of keratinizing colonies from single cells. Cell 6:331–343 (1975).

    Google Scholar 

  11. E. Bell, H. P. Ehrlich, D. J. Buttle and T. Nakatsuji. Living tissue formed in vitro and accepted as skin-equivalent tissue of full thickness. Science 211: 1052–1054 (1981).

    Google Scholar 

  12. M. Rosdy, B. Grisoni, and L. C. Clauss. Proliferation of normal human keratinocytes on silicone substrates. Biomaterials 12:511–517 (1991).

    Google Scholar 

  13. V. H. Mak, M. B. Cumpstone, A. H. Kennedy, C. S. Harmon, R. H. Guy, and R. O. Potts. Barrier function of human keratinocyte cultures grown at the air-liquid interface. J. Invest. Dermatol. 96:323–327 (1991).

    Google Scholar 

  14. N. Kim, M. El-Khalili, M. M. Henary, L. Strekowski, and B. B. Michniak. Percutaneous penetration enhancement activity of aromatic S, S-dimethyliminosulfuranes. Int. J. Pharm. 187:219–229 (1999).

    Google Scholar 

  15. B. B. Michiak, M. R. Player, J. M. Chapman, and J. W. Sowell. In vitro evaluation of a seies of Azone analogs as dermal penetration enhancers: I. Int. J. Pharm. 91:85–93 (1993).

    Google Scholar 

  16. L. C. Fuhrman, B. B. Michniak, C. R. Behl, and A. W. Malick. Effect of novel penetration enhancers on the transdermal delivery of hydrocortisone: an in vitro species comparison. J. Control. Rel. 45:197–204 (1996).

    Google Scholar 

  17. I. H. Blank, R. J. Scheuplein, and D. J. MacFarlane. Mechanism of percutaneous absorption. 3. The effect of temperature on the transport of non-electrolytes across the skin. J. Invest. Dermatol. 49:582–589 (1967).

    Google Scholar 

  18. C. A. Squier, P. Cox, and P. W. Wertz. Lipid content and water permeability of skin and oral mucosa. J. Invest. Dermatol. 96:123–126 (1991).

    Google Scholar 

  19. D. T. Downing, M. E. Stewart, P. W. Wertz, S. W. Colton, W. Abraham, and J. S. Strauss. Skin lipids: an update. J. Invest. Dermatol. 88:2s–6s (1987).

    Google Scholar 

  20. P. W. Wertz and D. T. Dowing. Stratum Corneum: Biological and biochemical considerations. In Transdermal Drug Delivery, J. Hadgraft and Richard H. Guy. Eds, Markel Dekker Inc., New York, 1989, pp. 1–22.

    Google Scholar 

  21. M. Ponec, A. Weerheim, J. Kempenaar, A. M. Mommaas, and D. H. Nugteren. Lipid composition of cultured human keratinocytes in relation to their differentiation. J. Lipid Res. 29:949–961 (1988).

    Google Scholar 

  22. M. Ponec. Reconstruction of human epidermis on deepidermized dermis: Expression of differentiation-specific protein markers and lipid composition, Toxicol. in Vitro. 5:597–606 (1991a).

    Google Scholar 

  23. P. W Wertz, and D. T. Downing. Glucosylceramides of pig epidermis: Structure determination. J. Lipid Res. 24:1135–1139 (1983).

    Google Scholar 

  24. P. W. Wertz and D. T. Downing. Acylglucosylceramides of pig epidermis: structure determination. J. Lipid Res. 24:753–758 (1983).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Asbill, C., Kim, N., El-Kattan, A. et al. Evaluation of a Human Bio-Engineered Skin Equivalent for Drug Permeation Studies. Pharm Res 17, 1092–1097 (2000). https://doi.org/10.1023/A:1026405712870

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026405712870

Navigation