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J Control Release. 2006 Aug 28;114(2):163-74. Epub 2006 Jun 17.

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

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Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, 985830 Nebraska Medical Center, Omaha, NE 68198-5830, USA.


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.

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