Percutaneous absorption of biologically-active interferon-gamma in a human skin graft-nude mouse model.

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-gamma) 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-gamma containing or lacking liposomes composed of phosphatidylcholine and cholesterol. Transport of rhIFN-gamma 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-gamma increased ICAM-1 levels in the epidermal basal and suprabasal cell layers of grafts. Continued application maintained this response. An aqueous formulation of rhIFN-gamma 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-gamma, into the epidermis of viable human skin. The therapeutic application of topical IFN-gamma delivery remains to be evaluated.