title: Preparation and biological properties of dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt)-loaded polymeric micelles.
abstract: Block copolymer micelles, containing dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt), the oxaliplatin parent complex, were prepared through polymer-metal complex formation of DACHPt with poly(ethylene glycol)-poly(glutamic acid) block copolymer [PEG-P(Glu)] in distilled water. By dynamic light scattering (DLS) measurement, the micelle size was determined to be 40 nm with narrow distribution. The release of platinum complexes from the micelle core was measured in phosphate buffer saline (pH 7.4) at 37 degrees C. DACHPt-loaded micelle showed a sustained release rate of platinum after an induction period of 12 h. In the same conditions, the kinetic stability of DACHPt-loaded micelle was measured. The micelle was found to be very stable, keeping the initial size, for 240 h. Against murine colon adenocarcinoma 26 (C-26) cells, DACHPt-loaded micelle exhibited considerable in vitro cytotoxicity, lower than oxaliplatin but increasing with exposure time as a result of the release of platinum complexes from the micelle. In vivo biodistribution assay performed on tumor-bearing mice demonstrated that the micelle showed prolonged blood circulation due to its high stability and high tumor accumulation for a prolonged time.
authors.affiliation: Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Horacio
authors.initials: H
authors.lastname: Cabral
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Soichiro
authors.initials: S
authors.lastname: Okazaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D051379:Mice; D008823:Micelles; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D009944:Organoplatinum Compounds; D011108:Polymers; C013933:dichloro-1,2-diaminocyclohexane platinum complex