Pluronic P123-Docetaxel Conjugate Micelles: Synthesis, Characterization, and Antitumor Activity

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 H-1-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 (R). Compared with Duopafei (R), 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.