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Percutaneous Absorption of Biologically-Active Interferon-gamma in a Human Skin Graft-Nude Mouse Model

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Abstract

Purpose. Topical delivery has been suggested to reduce systemic side effects while targeting cytokines for the treatment of certain skin conditions. Liposomes have been proposed as an enhancing agent for such a delivery. We have tested the potential of liposomes to augment the uptake of biologically active recombinant human interferon-gamma (rhIFN-γ) into human skin lacking adnexa in an in vivo model.

Methods. Stable grafts of human skin on nude mice were used to test aqueous formulations of rhIFN-γ containing or lacking liposomes composed of phosphatidylcholine and cholesterol. Transport of rhIFN-γ was assessed by monitoring the stimulated expression of intercellular adhesion molecule-1 (ICAM-1) by keratinocytes by light-level immunomicroscopy and ELISA.

Results. A single application of liposomal rhIFN-γ increased ICAM-1 levels in the epidermal basal and suprabasal cell layers of grafts. Continued application maintained this response. An aqueous formulation of rhIFN-γ or liposomes alone applied to grafts failed to induce an ICAM-1 response. Preliminary studies suggested that at least some of the lipids applied in the liposomal formulation also entered the epidermis.

Conclusions. Using a nude mouse-human skin graft model lacking adnexa, we have demonstrated that a liposomal formulation can augment the uptake of a biologically-active human cytokine, rhIFN-γ, into the epidermis of viable human skin. The therapeutic application of topical IFN-γ delivery remains to be evaluated.

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Authors and Affiliations

  1. Pharmaceutical Research and Development, Genentech Inc., 460 Pt. San Bruno Blvd., South San Francisco, California, 94080-4990

    Sarah M. Short & Ann L. Daugherty

  2. Department Pharmacology, University of North Carolina, Chapel Hill, North Carolina, 27599

    Sarah M. Short

  3. BioAnalytical Methods Development, Genentech Inc., South San Francisco, California, 94080-4990

    Brian D. Paasch & Jason H. Turner

  4. College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109-1065

    Norman Weiner

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  1. Sarah M. Short
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  4. Norman Weiner
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  5. Ann L. Daugherty
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  6. Randall J. Mrsny
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Short, S.M., Paasch, B.D., Turner, J.H. et al. Percutaneous Absorption of Biologically-Active Interferon-gamma in a Human Skin Graft-Nude Mouse Model. Pharm Res 13, 1020–1027 (1996). https://doi.org/10.1023/A:1016050422634

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