title: Development of the novel coating formulations for skin vaccination using stainless steel microneedle.
abstract: This study focused on the development of novel coating formulations for stainless steel microneedles against influenza A virus. With in vitro studies, various viscosity enhancers and stabilizers were screened based on the hemagglutination activity of the vaccine, which was coated and dried onto a stainless steel chip at room temperature for 1 day. Following the long-term storage test, the hemagglutination activity and particle size of the vaccine, which was formulated with conventional or methylcellulose or hydroxyethyl cellulose and dried onto the microneedle, were monitored. Next, to evaluate the in vivo immunogenicity and protection effect of each dried vaccine formulation, mice were immunized by the antigen-coated microneedle, which had either the conventional or the proposed formulation. Two novel formulations were chosen in the preliminary screening, and in further evaluations, they exhibited a 20 % higher HA activity during storage for 3 months, and no aggregation was observed during storage after drying. In a mouse model, the microneedle with the novel formulation elicited a higher level of IgG and IgG2a was more prevalent in the IgG isotype profile. In addition, mice immunized with the HEC-coated microneedle survived with small weight loss (>90 %) against lethal challenge infection. Overall, the novel formulation hydroxyethyl cellulose preserved significantly higher HA activity during the production and storage of the microneedle as well as improved the in vivo immunogenicity of the vaccine.
authors: Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
authors: Seong-Jin
authors: SJ
authors: Kim
authors: Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
authors: Ju-Hyung
authors: JH
authors: Shin
authors: Avian Disease Laboratory, College of Veterinary Medicine, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul, 143-701, Republic of Korea.
authors: Jin-Yong
authors: JY
authors: Noh
authors: Avian Disease Laboratory, College of Veterinary Medicine, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul, 143-701, Republic of Korea.
authors: Chang-Seon
authors: CS
authors: Song
authors: Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. dohnanyi@kaist.ac.kr.
authors: Yeu-Chun
authors: YC
authors: Kim
mesh_terms: D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004355:Drug Stability; D005260:Female; D006386:Hemagglutination Tests; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage; D007271:Injections, Intradermal; D008747:Methylcellulose / Q000737:chemistry; D051379:Mice; D009339:Needles; D013193:Stainless Steel / Q000737:chemistry*; D014611:Vaccination / Q000379:methods*; D014783:Viscosity
chemical_list: D007074:Immunoglobulin G; D007252:Influenza Vaccines; D013193:Stainless Steel; D002482:Cellulose; C002283:hydroxyethylcellulose; D008747:Methylcellulose
keywords: Coating formulation; Influenza; Long-term stability; Microneedle; Vaccine