title: Preparation of camptothecin-loaded polymeric micelles and evaluation of their incorporation and circulation stability.
abstract: To improve its aqueous solubility and stability in biological fluid, CPT was physically loaded in polymeric micelles. Polymeric micelles were composed of various poly(ethylene glycol)-poly(aspartate ester) block copolymers (PEG-P(Asp(R))). The incorporation and circulation stability of CPT micelles were evaluated by measuring the CPT in micelle using gel-permeation chromatography and by CPT concentration measurement after intravenous injection using HPLC, respectively, in terms of chemical structure of block copolymers. The stability of CPT-loaded micelles in vivo depended on the amount of benzyl esters, and length of PEG in the polymers to a greater degree than it did in vitro. A stable formulation of CPT-loaded micelles was obtained using PEG-P(Asp) with PEG of 5,000 (MW), 27 Asp units, and 57-75% benzyl esterification of Asp residue. This CPT-loaded micelles showed about a 17-fold lower blood clearance value than unstable micelles. The CPT-loaded micelles are potentially delivered to tumor sites owing to an extended circulation in the blood stream.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Praneet
authors.initials: P
authors.lastname: Opanasopit
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001224:Aspartic Acid / Q000737:chemistry; D001704:Biopolymers / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004355:Drug Stability; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008823:Micelles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001704:Biopolymers; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; C416210:poly(ethylene oxide)-block-poly(beta-benzyl aspartate); D001224:Aspartic Acid; D011092:Polyethylene Glycols; D002166:Camptothecin