Preparation and evaluation of self-assembly Soluplus^®-sodium cholate-phospholipid ternary mixed micelles of docetaxel

Abstract

Ternary mixed micelles constituted of Soluplus^®, sodium cholate, and phospholipid were prepared as nano-delivery system of the anticancer drug, docetaxel. The formulation of docetaxel-loaded ternary mixed micelles (DTX-TMMs) with an optimized composition (Soluplus^®/sodium cholate/phospholipid= 3:2:1 by weight) were obtained. The main particle size of DTX-TMMs was 76.36 ± 2.45 nm, polydispersity index (PDI) was 0.138 ± 0.039, and the zeta potential was −8.46 ± 0.55 mv. The encapsulation efficiency was 94.24 ± 4.30% and the drug loading was 1.25%. The critical micelle concentration value was used to assess the ability of carrier materials to form micelles. The results indicated that the addition of Soluplus^® to sodium cholate-phospholipid mixed micelles could reduce the critical micelle concentration and improve the stability. In vitro release studies demonstrated that compared with DTX-Injection group, the DTX-TMMs presented a controlled release property of drugs. In vivo pharmacodynamics results suggested that DTX-TMMs had the most effective inhibitory effect on tumor proliferation and had good biosafety. In addition, the relative bioavailability of mixed micelles was increased by 1.36 times compared with the DTX-Injection in vivo pharmacokinetic study indicated that a better therapeutic effect could be achieved. In summary, the ternary mixed micelles prepared in this study are considered to be promising anticancer drug delivery systems.

Keywords:

• Docetaxel
• ternary mixed micelles
• Soluplus^®
• CMC
• pharmacodynamics
• pharmacokinetics

Acknowledgements

We would like to express our gratitude to the Pharmacological Laboratory Center and the Animal Center of Shenyang Pharmaceutical University for their support.

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 under Grant (no. 81202480, 81302723), the Natural Science Foundation of Liaoning Province under Grant (no. 2015020749) and the Innovation training program for college students under Grant (no. 201710163000080).