title: Pluronic P123-docetaxel conjugate micelles: synthesis, characterization, and antitumor activity.
abstract: The purpose of this research is to develop and evaluate Pluronic P123 (P123)-docetaxel (DTX) conjugate that could form core-shell-type micelles in aqueous solution. DTX was covalently conjugated to P123 via ester bond after the activation of DTX by succinic anhydride. The structure of P123-DTX conjugate was confirmed by 1H-NMR. The self-assembly behavior of the P123-DTX conjugate in aqueous solution was characterized by the measurement of critical micelle concentration (CMC). The CMC of P123-DTX conjugate was (1.34 +/- 0.05) x 10(-5) mol/L, which was lower than that of P123 ((1.91 +/- 0.07) x 10(-5) mol/L). The DTX content in the conjugate could reach 13.69% (wt.%). TEM and DLS analysis showed that the conjugate formed approximately spherical micelles with mean particle size of 85.3 +/- 1.59 nm. In vitro release of DTX from the conjugate micelles showed pH dependence, being faster at lower pH value than that at pH 7.4. In vitro cytotoxicity of P123-DTX conjugate micelles was evaluated by MTT method against HepG2, MCF-7 and B16 cell lines and the result indicated that P123-DTX conjugate micelles showed lower cytotoxicity than the DTX injection-Duopafei. Compared with Duopafei, in vivo antitumor activity of P123-DTX conjugate micelles in Kunming mice bearing B16 tumor was more effective and less toxic. These results indicated that the P123-DTX conjugate micelles prepared in this study may be considered as an alternative and promising DTX delivery system.
authors.affiliation: School of Pharmaceutical Science, Shandong University, Ji'nan 250012, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Yutao
authors.initials: Y
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008823:Micelles; D058726:Nanoconjugates / Q000737:chemistry; D011060:Poloxalene / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D058726:Nanoconjugates; D043823:Taxoids; D000077143:Docetaxel; C464484:pluronic block copolymer P123; D011060:Poloxalene