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 e ffects while targeting cytokines for the treatment of certain skin con ditions. Liposomes have been proposed as an enhancing agent for such a delivery. We have tested the potential of liposomes to augment the up take of biologically active recombinant human interferon-gamma (rhIFN- gamma) into human skin lacking adnexa in an in vivo model. Methods. St able grafts of human skin on nude mice were used to test aqueous formu lations of rhIFN-gamma containing or lacking liposomes composed of pho sphatidylcholine and cholesterol. Transport of rhIFN-gamma was assesse d by monitoring the stimulated expression of intercellular adhesion mo lecule-1 (ICAM-1) by keratinocytes by light-level immunomicroscopy and ELISA. Results. A single application of liposomal rhIFN-gamma increas ed ICAM-1 levels in the epidermal basal and suprabasal cell layers of grafts. Continued application maintained this response. An aqueous for mulation of rhIFN-gamma or liposomes alone applied to grafts failed to induce an ICAM-1 response. Preliminary studies suggested that at leas t 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-gam ma, into the epidermis of viable human skin. The therapeutic applicati on of topical IFN-gamma delivery remains to be evaluated.