Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin

Jong Oh Kim, Alexander V. Kabanov, Tatiana K. Bronich

Research output: Contribution to journalArticle

196 Scopus citations

Abstract

Polymer micelles with cross-linked ionic cores were prepared by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) copolymer and divalent metal cations as templates. Doxorubicin (DOX), an anthracycline anticancer drug, was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. A substantial drug loading level (up to 50 w/w%) was achieved and it was strongly dependent on the structure of the cross-linked micelles and pH. The drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. The DOX-loaded polymer micelles exhibited noticeable pH-sensitive behavior with accelerated release of DOX in acidic environment due to the protonation of carboxylic groups in the cores of the micelles. The attempt to protect the DOX-loaded core with the polycationic substances resulted in the decrease of loading efficacy and had a slight effect on the release characteristics of the micelles. The DOX-loaded polymer micelles exhibited a potent cytotoxicity against human A2780 ovarian carcinoma cells. These results point to a potential of novel polymer micelles with cross-linked ionic cores to be attractive carriers for the delivery of DOX.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalJournal of Controlled Release
Volume138
Issue number3
DOIs
StatePublished - Sep 15 2009

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Keywords

  • Block copolymer micelles
  • Core-shell morphology
  • Doxorubicin
  • Self-assembly

ASJC Scopus subject areas

  • Pharmaceutical Science

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