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

Int J Nanomedicine. 2012:7:2557-71. doi: 10.2147/IJN.S29145. Epub 2012 Jun 8.

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.

Keywords: block ionomer complex; cisplatin; cross-linked micelle; drug delivery; ovarian cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / toxicity
  • Cisplatin / administration & dosage*
  • Cisplatin / pharmacokinetics
  • Cisplatin / toxicity
  • Drug Carriers / administration & dosage*
  • Drug Carriers / pharmacokinetics
  • Drug Carriers / toxicity
  • Female
  • Hemolysis / drug effects
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Micelles*
  • Nanomedicine
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Polyethylene Glycols / chemistry
  • Polymethacrylic Acids / chemistry
  • Tissue Distribution / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Micelles
  • Polymethacrylic Acids
  • Polyethylene Glycols
  • Cisplatin