A novel micelle-encapsulated platinum(II) anticancer agent

Vithal B. Jadhav, Yong Joo Jun, Ju Hee Song, Min Kyoung Park, Ji Hyun Oh, Song Wha Chae, In Sun Kim, Soo Jin Choi, Hwa Jeong Lee, Youn Soo Sohn

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

A hydrophobic and water-insoluble platinum(II) compound, cis-(cha)2Pt(NO3)2 was encapsulated by macromolecular micelles self-assembled from an amphiphilic cyclotriphosphazene [NP(MPEG750)(GlyPheLeu)2Et]3 (CP750). The micelle-encapsulated platinum(II) compound exhibited outstanding pharmacokinetics in rats by showing long blood circulation and much larger systemic exposure (AUC=43.5μgh/ml) compared with the free carboplatin (AUC=4.32μgh/ml). Biodistribution study of the micellar platinum(II) compound using male Sprague-Dawley rats has shown excellent tumor to tissue ratios of 4.03 at 2h post injection and 4.67 at 24h post injection. Furthermore, the micellar platinum(II) compound exhibited more than 6 times higher cellular uptake in human cervical (HeLa) and lung (A549) tumor cells compared with the free platinum compound. Also it is surprising that the micellar platinum(II) compound displayed specifically high cytotoxicity against the stomach tumor cells (SNU638), which are one of the least responsive to chemotherapeutic agents currently in clinical use. The acute toxicity study has shown that the LD50 values of free and the micellar cis-(cha)2Pt(NO3)2 are approximately 70mg/kg and 90mg/kg, respectively. Thus the platinum compound encapsulated by cyclotriphosphazene micelles is a promising candidate for preclinical studies.

Original languageEnglish
Pages (from-to)144-150
Number of pages7
JournalJournal of Controlled Release
Volume147
Issue number1
DOIs
StatePublished - Oct 2010

Keywords

  • Anticancer drug
  • Cis-bis(cyclohexylamine)dinitratoplatinum
  • Cyclotriphosphazene
  • Micelle
  • Platinum drug

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