TRANSPORT OF BIOLOGICALLY-ACTIVE INTERFERON-GAMMA ACROSS HUMAN SKIN IN-VITRO

Purpose. Several studies have suggested epidermal uptake of cytokines, such as interferons, can be facilitated using topical liposomal formu lations. We have evaluated the in vitro transport of biologically acti ve recombinant human interferon-gamma (rhIFN-gamma) into and through s plit-thickness human skin to assess this possibility. Methods. Skin sa mples were exposed to rhIFN-gamma under various conditions involving h ydrated and dry surface conditions in the presence and absence of lipo somes. A new low-level ELISA and an anti-viral bioassay were used to q uantitate transported rhIFN-gamma. Immunohistochemical staining for IC AM-1 expression by keratinocytes was used to visualize the extent and distribution of rhIFN-gamma transport. Results. Apparent steady-state transport of rhIFN-gamma occurred within the first 5 hours of exposure with approximately 10% of transported rhIFN-gamma demonstrating bioac tivity. While the permeability of rhIFN-gamma across human skin under drying conditions was enhanced by the presence of liposomes, no augmen tation of permeability was observed when the skin was kept hydrated. L iposomal formulations of rhIFN-gamma had greater transport rates than aqueous formulations when the applied formulations were allowed to dry after dosing. Conclusions. Our results demonstrate the transport of b iologically active rhIFN-gamma across human skin in vitro and suggest a role for stratum corneum hydration as one possibility for the augmen ted cytokine transport.