title: Development of a novel self-dissolving microneedle array of alendronate, a nitrogen-containing bisphosphonate: evaluation of transdermal absorption, safety, and pharmacological effects after application in rats.
abstract: Alendronate is a nitrogen-containing bisphosphonate that is widely used for the treatment of osteoporosis. In this study, we developed a novel self-dissolving micron-size needle array (microneedle array) containing alendronate, which was fabricated by micromodeling technologies using hyaluronic acid as a basic material. Micron-scale pores in the skin were seen after the application of the alendronate-loaded microneedle array, verifying establishment of transdermal pathways for alendronate. The absorption of alendronate after the application of alendronate-loaded microneedle array was almost equivalent to that after subcutaneous administration, and the bioavailability of alendronate was approximately 90% in rats. Furthermore, delivery of alendronate via this strategy effectively suppressed the decrease in the width of the growth plate in a rat model of osteoporosis. Although mild cutaneous irritation was observed after the application of the alendronate-loaded microneedle array, it resolved by day 15. These findings indicate that this alendronate-loaded microneedle array is a promising transdermal formulation for the treatment of osteoporosis.
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Katsumi
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kaori
authors.initials: K
authors.lastname: Hitomi
authors.forename: Rie
authors.initials: R
authors.lastname: Hayashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hirai
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.forename: Ying-shu
authors.initials: YS
authors.lastname: Quan
authors.forename: Fumio
authors.initials: F
authors.lastname: Kamiyama
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sakane
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000279:Administration, Cutaneous; D019386:Alendronate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001682:Biological Availability; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004304:Dosage Forms; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D006132:Growth Plate / Q000187:drug effects* / Q000473:pathology; D006820:Hyaluronic Acid / Q000737:chemistry*; D008297:Male; D008904:Miniaturization; D009339:Needles; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010052:Ovariectomy; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012869:Skin Absorption; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D050071:Bone Density Conservation Agents; D004304:Dosage Forms; D006820:Hyaluronic Acid; D019386:Alendronate