two-and three-layered dissolving microneedles for transcutaneous delivery of model vaccine antigen in rats还有三层溶解微经皮的交付模型疫苗抗原的老鼠.pdf

Journal of Biomaterials and Nanobiotechnology, 2012, 3, 325-334 325 /10.4236/jbnb.2012.33030 Published Online July 2012 (http://www.SciRP.org/journal/jbnb) Two- and Three-Layered Dissolving Microneedles for Transcutaneous Delivery of Model Vaccine Antigen in Rats 1 1 2 1 Asuka Ikejiri , Yukako Ito , Seishiro Naito , Kanji Takada 1Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto, Japan; 2Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan. Email: asukaikejiri@yahoo.co.jp, takada@mb.kyoto-phu.ac.jp Received March 9th, 2012; revised April 15th, 2012; accepted May 8th, 2012 ABSTRACT Purpose: Comparison of transcutaneous immunization of ovalbumin (OA) between two- and three-layered dissolving microneedles (MN) in rats. Methods: We prepared 500 μm long two-layered and three-layered dissolving microneedle (2-MN and 3-MN, respectively) arrays from chondroitin sulfate as the base, and OA as the model antigen. The 2-MN containing OA at the acral portion and 3-MN with OA at the second portion were administered to rat skin transcuta- neously. As a positive control, OA solution was injected subcutaneously (sc). The OA delivery and diffusion in the rat skin were studied using confocal microscopy with fluorescein-conjugated OA (FL-OA). Results: The formulated posi- tions of OA were 0 - 155 ± 5 μm for 2-MN and 175 ± 4 - 225 ± 5 μm for 3-MN. The administered doses of OA were 2.2 ± 0.1 μg, 12.0 ± 0.2 μg and 22.0 ± 0.2 μg for 2-MN, 1.8 ± 0.2 μg, 12.6 ± 0.7 μg, and 20.4 ± 0.3 μg for 3-MN, 10 μg, 100 μg and 1000 μg for sc injection. At 4 weeks after the first administration, 3-MN showed about 2.5 - 7.0 fold and 5.4 fold higher total Ig(G + A + M) antibody than 2-MN and sc injection of the OA solution. Conclusions: The 3-MN, whi