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

JOURNAL OF CONTROLLED RELEASE

卷:138

Article; Proceedings Paper

Kim, Jong Oh^1,2  Kabanov, Alexander V.^1,2,3  Bronich, Tatiana K.^1,2 

[1] Univ Nebraska Med Ctr, Coll Pharm, Dept Pharmaceut Sci, Omaha, NE 68198 USA

[2] Univ Nebraska Med Ctr, Coll Pharm, Ctr Drug Delivery & Nanomed, Omaha, NE 68198 USA

[3] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia

关键词: Block copolymer micelles;    Doxorubicin;    Self-assembly;    Core-shell morphology;   

DOI  :  10.1016/j.jconrel.2009.04.019

来源: Elsevier

【 摘 要 】

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. (c) 2009 Elsevier B.V. All rights reserved.

【 授权许可】

Free