title: Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin.
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.
authors.affiliation: 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.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Bronich
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D002277:Carcinoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006801:Humans; D008823:Micelles; D010051:Ovarian Neoplasms / Q000188:drug therapy; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D004317:Doxorubicin; D004337:Drug Carriers; D008823:Micelles; D000071228:Polyelectrolytes; D011108:Polymers