title: Characterization and anti-tumor activity of chemical conjugation of doxorubicin in polymeric micelles (DOX-P) in vitro.
abstract: Characterization and anti-tumor activity of chemical conjugation of doxorubicin (DOX) in polymeric micelles were investigated. Polymeric micelles with chemical conjugation of doxorubicin (DOX-P) were prepared. Succinic anhydride activated pluronic F68 was first synthesized and the primary amine group in doxorubicin was conjugated to the terminal carboxyl of pluronic F68 via a amide. The resulting polymeric micelles in aqueous solution were characterized by measurement of size, ξ-potential, drug loading and critical micelle concentration. From characterization results, DOX-P micelles had superiorities over physically-loaded DOX micelles in loading efficiency, diameter and CMC value. From drug release experiment in vitro, DOX-P micelles reached a sustained release profile for DOX. The cytotoxic activity of the micelles against A549/DOX cells was greater than free DOX. Fluorescence microscope observation and flow cytometry analysis supported the enhanced cellular uptake of the micelles. From A549/DOX cells experiments, DOX-P micelles could enhance DOX anti-tumor activity and circumvent the multi-drug resistance (MDR) of A549/DOX cells. With low CMC value, high loading efficiency, nanometer diameter, good penetration ability and controlled release behaviour, DOX-P micelles might be developed as a new cancer targeted delivery system.
authors.affiliation: Wenzhou Medical College, Wenzhou City, Zhejiang Province, China.
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
authors.forename: Chang-Zheng
authors.initials: CZ
authors.lastname: Sun
authors.forename: Cui-Tao
authors.initials: CT
authors.lastname: Lu
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Dai
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Lv
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Chang-Wei
authors.initials: CW
authors.lastname: Wan
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008823:Micelles; D011108:Polymers
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D004317:Doxorubicin