title: Polymer micelles with cross-linked ionic cores for delivery of anticancer drugs.
abstract: 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.
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: Satya
authors.initials: S
authors.lastname: Bontha
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Bronich
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems; D024202:Electrophoretic Mobility Shift Assay; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D011108:Polymers; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008823:Micelles; D011108:Polymers; D002945:Cisplatin