Avaji, Prakash G. Joo, Hye In Park, Jung Hyun Park, Kyung Su Jun, Yong Joo Lee, Hwa Jeong Sohn, Youn Soo 2024-01-20T08:32:40Z 2024-01-20T08:32:40Z 2021-09-02 2014-11 0162-0134 https://pubs.kist.re.kr/handle/201004/126175 Aiming at tumor targeting delivery of oxaliplatin using polymer therapy, a new monomeric platinum(II) complex (dach)Pt[HEDM] (dach: trans-(+/-)-1,2-diaminocyclohexane; HEDM: 2-hydroxyethoxydiethylmalate) was designed to include the antitumor moiety (dach)Pt and HEDM as a linker to the polyphosphazene backbone. This monomeric Pt-complex could easily be grafted to the PEGylated polyphosphazene backbone to prepare a novel polyphosphazene-Pt conjugate, [NP(MPEG550)(dach)Pt(EM)](n), [MPEG550: methoxy poly(ethylene glycol) with an average molecular weight of 550; EM: ethoxymalate]. This amphiphilic polyphosphazene-Pt conjugate was found to self-assemble into stable polymeric micelles of a mean diameter of 130 nm, which is suitable for passive tumor targeting by enhanced permeability and retention (EPR) effect. Pharmacokinetic study of this polymer conjugate exhibited long blood circulation as expected and longer half-life (t(1/2)beta = 9.52 h) compared with oxaliplatin (3.47 h), and much larger AUC (area under the curve) value (25,831 ng.h/mL) compared with oxaliplatin (1194 ng.h/mL). Biodistribution study of the polymer conjugate has shown excellent tumor selectivity with the tumor to tissue ratio of 3.84 at 2 h post injection and 11.7 at 24 h post injection probably due to the EPR effect of the polymer conjugate while no tumor selectivity was observed for monomeric oxaliplatin. Furthermore, accumulation of this polymer conjugate in kidney was much lower compared with oxaliplatin. Also the nude mouse xenograft trial of the polymer conjugate has shown higher antitumor efficacy compared with oxaliplatin. (C) 2014 Elsevier Inc. All rights reserved. English ELSEVIER SCIENCE INC ANTITUMOR-ACTIVITY CISPLATIN DELIVERY NEPHROTOXICITY PERMEABILITY NANOCAPSULES COPOLYMER Synthesis and properties of a new micellar polyphosphazene-platinum(II) conjugate drug Article 10.1016/j.jinorgbio.2014.06.014 1 JOURNAL OF INORGANIC BIOCHEMISTRY, v.140, pp.45 - 52 JOURNAL OF INORGANIC BIOCHEMISTRY 140 45 52 scie scopus 000342608900007 2-s2.0-84905171978 Biochemistry & Molecular Biology Chemistry, Inorganic & Nuclear Biochemistry & Molecular Biology Chemistry Article ANTITUMOR-ACTIVITY CISPLATIN DELIVERY NEPHROTOXICITY PERMEABILITY NANOCAPSULES COPOLYMER Platinum drug Polymer conjugate Polyphosphazene Polymer micelle Oxaliplatin