Transport of Biologically Active Interferon-gamma Across Human Skin in Vitro

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Abstract
Purpose. Several studies have suggested epidermal uptake of cytokines, such as interferons, can be facilitated using topical liposomal formulations. We have evaluated the in vitro transport of biologically active recombinant human interferon-γ (rhIFN-γ) into and through split-thickness human skin to assess this possibility. Methods. Skin samples were exposed to rhIFN-γ under various conditions involving hydrated and dry surface conditions in the presence and absence of liposomes. A new low-level ELISA and an anti-viral bioassay were used to quantitate transported rhIFN-γ. Immunohistochemical staining for ICAM-1 expression by keratinocytes was used to visualize the extent and distribution of rhIFN-γ transport. Results. Apparent steady-state transport of rhIFN-γ occurred within the first 5 hours of exposure with approximately 10% of transported rhIFN-γ demonstrating bioactivity. While the permeability of rhIFN-γ across human skin under drying conditions was enhanced by the presence of liposomes, no augmentation of permeability was observed when the skin was kept hydrated. Liposomal formulations of rhIFN-;γ had greater transport rates than aqueous formulations when the applied formulations were allowed to dry after dosing. Conclusions. Our results demonstrate the transport of biologically active rhIFN-γ across human skin in vitro and suggest a role for stratum corneum hydration as one possibility for the augmented cytokine transport.