title: Core cross-linked block ionomer micelles as pH-responsive carriers for cis-diamminedichloroplatinum(II).
abstract: 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 amphiphilic 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.
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: Hardeep S
authors.initials: HS
authors.lastname: Oberoi
authors.forename: Frederic C
authors.initials: FC
authors.lastname: Laquer
authors.forename: Luis A
authors.initials: LA
authors.lastname: Marky
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* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D008823:Micelles; D002945:Cisplatin