Polysialic acid and pluronic F127 mixed polymeric micelles of docetaxel as new approach for enhanced antitumor efficacy

Abstract

In our previous study, polysialic acid-octadecyl dimethyl betaine (PSA-BS18) was synthesized and modified to liposomal EPI. Preliminary experiments revealed that the PSA-BS18 was a potential material for targeting tumor site with superior curative effects. In this study, PSA-BS18 and Pluronic F127 (F127) mixed polymeric micelles encapsulated docetaxel (DTX) (FP/DTX) were prepared by a self-assembly method. The FP/DTX was found to have a diameter of 34.83 ± 0.50 nm with a narrow polydispersity, the entrapment efficiency was 99.12 ± 1.17%, and the drug loading efficiency of 1.40 ± 0.01%. The storage and dilution stability of FP/DTX was fine. In vitro release studies demonstrated that FP/DTX had delayed the drug release from the micelles. In vitro cytotoxicity assay on B16 cells presented that FP/DTX led to a stronger cytotoxic activity in comparison to F127 micelles based DTX (F127/DTX) and Tween80-based DTX (Taxotere^®). The in vivo imaging study showed that the accumulation of FP/DTX at tumor sites was more than F127/DTX. The in vivo antitumor activity of FP/DTX against B16 tumor xenograft model showed a significant higher inhibition and a lower toxicity compared with F127/DTX and Taxotere^®. Taken together, the results obtained above showed that PSA-BS18 and F127 mixed polymeric micelles may be a promising strategy for antitumor delivery of DTX.

Keywords:

• Pluronic F127
• docetaxel
• polysialic acid-octadecyl dimethyl betaine
• micelle
• antitumor activity

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (grant no. 81373334).