Polymer micelles with cross-linked ionic cores for delivery of anticancer drugs

J Control Release. 2006 Aug 28;114(2):163-74. doi: 10.1016/j.jconrel.2006.06.015. Epub 2006 Jun 17.

Abstract

This work reports the design of polymer micelles with cross-linked ionic cores that display high stability. Block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) copolymer and divalent metal cations were utilized as micellar templates for the synthesis of the cross-linked micelles. Such micelles represent hydrophilic nanospheres of core-shell morphology. The core comprises a network of the cross-linked polyanions, which is surrounded by the shell of hydrophilic PEO chains. The ionic character of the core provided for pH-dependent swelling/collapse behavior of the nanogels. Cisplatin, a potent chemotherapeutic agent, was incorporated into the ionic core of the micelles with remarkably high efficiency (22% w/w). The drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. Slow release of platinum complexes was observed in sustained manner from the cisplatin-loaded cross-linked micelles in physiological saline. In vitro studies using human A2780 ovarian carcinoma cells demonstrated that the cross-linked micelles rapidly internalized and delivered cisplatin into cells. These results indicated that polymer micelles with cross-linked ionic cores are promising for further fundamental material studies and practical applications as drug delivery carriers.

Publication types

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

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Cell Line, Tumor
  • Chemical Phenomena
  • Chemistry, Physical
  • Cisplatin / administration & dosage
  • Cisplatin / chemistry
  • Cross-Linking Reagents
  • Drug Delivery Systems
  • Electrophoretic Mobility Shift Assay
  • Fluoresceins
  • Fluorescent Dyes
  • Humans
  • Magnetic Resonance Spectroscopy
  • Micelles
  • Microscopy, Atomic Force
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Polymers
  • Spectrophotometry, Ultraviolet

Substances

  • Antineoplastic Agents
  • Cross-Linking Reagents
  • Fluoresceins
  • Fluorescent Dyes
  • Micelles
  • Polymers
  • Cisplatin