Macroflux (R) microprojection array patch technology: A new and efficient approach for intracutaneous immunization

Purpose. We evaluated the Macroflux(R) microprojection array patch technology as a novel system for intracutaneous delivery of protein antigens. Methods. Macroflux(R) microprojection array systems (330-mum microprojection length, 190 microprojections/cm(2), 1- and 2-cm(2) 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(R) microprojections penetrated into hairless guinea pig skin at an average depth of 100 mum with no projections deeper than 300 mum, Doses of 1 to 80 mug of OVA were delivered via 1- or 2-cm(2) systems by varying the coating solution concentration and wearing time. Delivery rates were as high as 20 mug in 5 s. In a prime and boost dose immune response study, OVA-coated Macroflux(R) 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 (I and 5 mug). Macroflux(R) administration at 1- and 5-mug 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(R) resulted in augmented antibody responses. Conclusions. Macroflux(R) 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.