Transport of biologically active interferon-gamma across human skin in vitro.
OBJECTIVE
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-gamma (rhIFN-gamma) into and through split-thickness human skin to assess this possibility.


METHODS
Skin samples were exposed to rhIFN-gamma 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-gamma. Immunohistochemical staining for ICAM-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 bioactivity. While the permeability of rhIFN-gamma 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-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 biologically active rhIFN-gamma across human skin in vitro and suggest a role for stratum corneum hydration as one possibility for the augmented cytokine transport.
D000328:Adult; D001692:Biological Transport; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000008:administration & dosage / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011994:Recombinant Proteins; D012869:Skin Absorption / Q000502:physiology*
D004337:Drug Carriers; D008081:Liposomes; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma