title: General considerations regarding the in vitro and in vivo properties of block copolymer micelle products and their evaluation.
abstract: Block copolymer micelles are nanoparticles formed from block copolymers that comprise a hydrophilic polymer such as poly(ethylene glycol) and a poorly soluble polymer such as poly(amino acids). The design of block copolymer micelles is intended to regulate the in vivo pharmacokinetics, stability, and distribution profiles of an entrapped or block copolymer-linked active substance. Several block copolymer micelle products are currently undergoing clinical development; however, a major challenge in the development and evaluation of such products is identification of the physicochemical properties that affect the properties of the drug product in vivo. Here we review the overall in vitro and in vivo characteristics of block copolymer micelle products with a focus on the products currently under clinical investigation. We present examples of methods suitable for the evaluation of the physicochemical properties, non-clinical pharmacokinetics, and safety of block copolymer micelle products.
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. Electronic address: kumikato@nihs.go.jp.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Sakai-Kato
authors.affiliation: Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuda, Midori, Yokohama 226-8503, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Kowa Co., Ltd., 332-1, Ohnoshinden, Fuji-shi, Shizuoka 417-8650, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kozaki
authors.affiliation: Nippon Kayaku Co., Ltd., 3-31-12 Shimo, Kita-ku, Tokyo 115-8588, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: Pharmaceuticals and Medical Devices Agency, 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Pharmaceuticals and Medical Devices Agency, 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Hirano
authors.affiliation: NanoCarrier Co., Ltd., Chuou 144-15, 226-39 Wakashiba, Kashiwa, Chiba 277-0871, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hanada
authors.affiliation: ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa 213-8522, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hisada
authors.affiliation: Pharmaceuticals and Medical Devices Agency, 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onodera
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
authors.affiliation: Division of Developmental Therapeutics, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Goda
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawanishi
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D008823:Micelles; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D008823:Micelles; D011108:Polymers
keywords: Block copolymer micelle; Drug development; Nanotechnology; Regulatory affairs