Percutaneous absorption of biologically-active interferon-gamma in a human skin graft-nude mouse model.
OBJECTIVE
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.
Short
S M
SM
Genentech Inc., South San Francisco, California 94080-4990, USA.
Paasch
B D
BD
Turner
J H
JH
Weiner
N
N
Daugherty
A L
AL
Mrsny
R J
RJ
D000818:Animals; D001692:Biological Transport; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D010539:Permeability; D011994:Recombinant Proteins; D012869:Skin Absorption / Q000502:physiology*; D016038:Skin Transplantation
D004337:Drug Carriers; D008081:Liposomes; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma