title: Development and clinical study of a self-dissolving microneedle patch for transcutaneous immunization device.
abstract: OBJECTIVE
  We previously reported the safety and efficacy in animal experiments of transcutaneous immunization (TCI) using a self-dissolving microneedle patch (MicroHyala; MH) made of hyaluronic acid and collagen. However, this MH was an unsuitable TCI device for the human skin, as collagen is suspected to induce inflammation. In this study, we developed an improved collagen-free MH (new-MH) and conducted clinical study to evaluate the fundamental properties and safety in human.
  
  
  METHODS
  Microneedle dissolution, skin irritation, and antigen-specific antibody production about new-MH were measured in mice and/or rats. On the basis of the results, the clinical study was conducted in healthy volunteers to evaluate local and systemic adverse events caused by new-MH application.
  
  
  RESULTS
  We confirmed that the microneedles of new-MH, as well as those on our old-MH that contained collagen, could easily pierce stratum corneum without severe skin irritation, and that TCI using new-MH efficiently increased antibody titer with comparable to TCI using old-MH. Application of new-MH caused no severe adverse reactions in 20 healthy volunteers enrolled in a clinical study.
  
  
  CONCLUSIONS
  These results verified that new-MH is a safe TCI device in human, and greatly encouraged us to advance PI/PII clinical studies of antigen-loaded new-MH.
authors.affiliation: Laboratory of Biotechnology and Therapeutics Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirobe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Azukizawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuo
authors.forename: You
authors.initials: Y
authors.lastname: Zhai
authors.forename: Ying-Shu
authors.initials: YS
authors.lastname: Quan
authors.forename: Fumio
authors.initials: F
authors.lastname: Kamiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
authors.forename: Naoki
authors.initials: N
authors.lastname: Okada
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000818:Animals; D004168:Diphtheria Toxoid / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D017097:Electric Impedance; D004867:Equipment Design; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D023422:Skin Irritancy Tests; D013745:Tetanus Toxoid / Q000008:administration & dosage; D057968:Transdermal Patch / Q000009:adverse effects; D014611:Vaccination / Q000295:instrumentation* / Q000379:methods
chemical_list: D004168:Diphtheria Toxoid; D007074:Immunoglobulin G; D013745:Tetanus Toxoid