Synthesis and properties of a new micellar polyphosphazene-platinum(II) conjugate drug

Prakash G. Avaji, Hye In Joo, Jung Hyun Park, Kyung Su Park, Yong Joo Jun, Hwa Jeong Lee, Youn Soo Sohn

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 (t1/2β = 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.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalJournal of Inorganic Biochemistry
StatePublished - Nov 2014

Bibliographical note

Funding Information:
This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea ( HI11C0532 ) and by National Research Foundation of Korea (NRF) Grant funded by the Korean Government ( MEST ) ( NRF-2011-0013493 ).


  • Oxaliplatin
  • Platinum drug
  • Polymer conjugate
  • Polymer micelle
  • Polyphosphazene


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