Macroflux microprojection array patch technology: a new and efficient approach for intracutaneous immunization.

Abstract

PURPOSE: We evaluated the Macroflux microprojection array patch technology as a novel system for intracutaneous delivery of protein antigens. METHODS: Macroflux microprojection array systems (330-microm micro-projection length, 190 microprojections/cm2, 1- and 2-cm2 area) were coated with a model protein antigen, ovalbumin (OVA), to produce a dry-film coating. After system application, microprojection penetration depth, OVA delivery, and comparative immune responses were evaluated in a hairless guinea pig model. RESULTS: Macroflux microprojections penetrated into hairless guinea pig skin at an average depth of 100 microm with no projections deeper than 300 microm. Doses of I to 80 microg of OVA were delivered via 1- or 2-cm2 systems by varying the coating solution concentration and wearing time. Delivery rates were as high as 20 microg in 5 s. In a prime and boost dose immune response study, OVA-coated Macroflux was most comparable to equivalent doses injected intradermally. Higher antibody titers were observed when OVA was administered with the microprojection array or intradermally at low doses (1 and 5 microg). Macroflux administration at 1- and 5-microg doses gave immune responses up to 50-fold greater than that observed after the same subcutaneous or intramuscular dose. Dry coating an adjuvant, glucosaminyl muramyl dipeptide, with OVA on the Macroflux resulted in augmented antibody responses. CONCLUSIONS: Macroflux skin patch technology provides rapid and reproducible intracutaneous administration of dry-coated antigen. The depth of skin penetration targets skin immune cells; the quantity of antigen delivered can be controlled by formulation, patch wearing time, and system size. This novel needle-free patch technology may ultimately have broad applications for a wide variety of therapeutic vaccines to improve efficacy and convenience of use.