Cisplatin-loaded core cross-linked micelles: Comparative pharmacokinetics, antitumor activity, and toxicity in mice

Hardeep S. Oberoi, Natalia V. Nukolova, Frederic C. Laquer, Larisa Y. Poluektova, Jiangeng Huang, Yazen Alnouti, Masanao Yokohira, Lora L. Arnold, Alexander V. Kabanov, Samuel M. Cohen, Tatiana K. Bronich

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Polymer micelles with cross-linked ionic cores are shown here to improve the therapeutic performance of the platinum-containing anticancer compound cisplatin. Biodistribution, antitumor efficacy, and toxicity of cisplatin-loaded core cross-linked micelles of poly(ethylene glycol)-b-poly(methacrylic acid) were evaluated in a mouse ovarian cancer xenograft model. Cisplatin-loaded micelles demonstrated prolonged blood circulation, increased tumor accumulation, and reduced renal exposure. Improved antitumor response relative to free drug was seen in a mouse model. Toxicity studies with cisplatin-loaded micelles indicate a significantly improved safety profile and lack of renal abnormalities typical of free cisplatin treatment. Overall, the study supports the fundamental possibility of improving the potential of platinum therapy using polymer micelle-based drug delivery.

Original languageEnglish (US)
Pages (from-to)2557-2571
Number of pages15
JournalInternational journal of nanomedicine
Volume7
DOIs
StatePublished - 2012

Keywords

  • Block ionomer complex
  • Cisplatin
  • Cross-linked micelle
  • Drug delivery
  • Ovarian cancer

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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