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  • Title: Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin.
    Author: Kim JO, Kabanov AV, Bronich TK.
    Journal: J Control Release; 2009 Sep 15; 138(3):197-204. PubMed ID: 19386272.
    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.
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