Journal
JOURNAL OF CONTROLLED RELEASE
Volume 153, Issue 1, Pages 64-72Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2011.03.028
Keywords
Cisplatin; Block copolymers; Cross-linking; Drug delivery; Micelle
Funding
- National Institutes of Health (NIH) [CA116590, RR021937]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1122029] Funding Source: National Science Foundation
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Benefits of the frequently prescribed platinum (II) chemotherapy drugs are compromised by undesirable side effects, poor pharmacokinetics and development of drug resistance. Polymer micelles derived from amphiphillic block copolymers, offer a novel macromolecular platform for carrier based delivery of such compounds. Soft polymeric nanocarriers were synthesized by template-assisted method involving condensation of the poly(ethylene oxide)-b-polymethacrylate anions by metal ions into core-shell block ionomer complex micelles followed by chemical cross-linking of the polyion chains in the micelle cores. The resulting micelles can efficiently incorporate cisplatin with a high loading capacity (up to 42% w/w). Core cross-linking stabilized the micelles against structural disintegration and prevented premature drug release. The reversible cisplatin entrapment involved the carboxylate groups of the micellar core. The drug was released in a pH-responsive manner, without loss of its biological activity. The stable cross-linked polymer micelles can potentially improve platinum (II) drug disposition with improved therapeutic potential. (C) 2011 Elsevier B.V. All rights reserved.
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