title: Improvement of Transdermal Delivery of Exendin-4 Using Novel Tip-Loaded Microneedle Arrays Fabricated from Hyaluronic Acid.
abstract: The purpose of this study was to evaluate the characteristics of exendin-4 tip-loaded microneedle arrays and to compare their acute efficacy with subcutaneous injections in type 2 diabetic GK/Slc rats. Fluorescein isothiocyanate labeled dextran with an average molecular weight of 4,000 (FD4) was selected as a model drug, and FD4 tip-loaded microneedle arrays were prepared in this study. In addition, intraperitoneal glucose tolerance tests after application of exendin-4 tip-loaded microneedle arrays were also compared with those after subcutaneous injection in type 2 diabetic GK/Slc rats. The release of FD4 from the tip-loaded microneedle arrays was very rapid, particularly in the initial 30 s, and most of the FD4 was released within 5 min. In addition, glucose tolerance was improved and the insulin secretion was enhanced after application of exendin-4 tip-loaded microneedle arrays, and these effects were comparable to those after subcutaneous injection of exendin-4. Similar plasma concentration profiles were seen after application of exendin-4 tip-loaded microneedle arrays, as was the case with subcutaneous injection in type 2 diabetic GK/Slc rats. These findings indicate that exendin-4 tip-loaded microneedle arrays can be used as an alternative to achieve sufficient delivery of exendin-4 for treatment of type 2 diabetes. To our knowledge, this is the first report of transdermal exendin-4 delivery using tip-loaded microneedle arrays.
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.|CosMED Pharmaceutical Co. Ltd , Higashikujo Kawanishi-cho 32, Minami-ku, Kyoto 601-8014, Japan.
authors.forename: Ying-Shu
authors.initials: YS
authors.lastname: Quan
authors.affiliation: CosMED Pharmaceutical Co. Ltd , Higashikujo Kawanishi-cho 32, Minami-ku, Kyoto 601-8014, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kamiyama
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Katsumi
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sakane
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000077270:Exenatide; D006820:Hyaluronic Acid / Q000737:chemistry*; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D014688:Venoms / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D010455:Peptides; D014688:Venoms; D006820:Hyaluronic Acid; D000077270:Exenatide
keywords: absorption; exendin-4; hyaluronic acid; microneedle array; peptide delivery; percutaneous; protein delivery; skin; transdermal absorption; transdermal drug delivery