Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin.
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.
Kim
Jong Oh
JO
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.
Kabanov
Alexander V
AV
Bronich
Tatiana K
TK
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*
D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D004317:Doxorubicin; D004337:Drug Carriers; D008823:Micelles; D000071228:Polyelectrolytes; D011108:Polymers