Application of a novel multicomponent nanoemulsion to tumor therapy Based on the theory of “unification of drugs and excipients”

Abstract

Toad skin has many pharmacological activities and bufadienolides are regarded as its main anti-tumor components. The poor water solubility, high toxicity, rapid elimination and less selectivity in vivo of bufadienolides limit the application of toad skin. Based on the “unification of drugs and excipients” theory, the toad skin extracts (TSE) and Brucea javanica oil (BJO) nanoemulsions (NEs) were designed to solve the aforementioned problems. BJO as the main oil phase was not only used to prepare the NEs, but played a synergistic therapeutic role combined with TSE. TSE-BJO NEs showed 155 nm particle size, entrapment efficiency of >95% and good stability. TSE-BJO NEs demonstrated superior anti-tumor activity compared with the TSE or BJO NEs alone. The mechanism of TSE-BJO NEs to enhance the antineoplastic efficacy involved several pathways, such as inhibiting cell proliferation, inducing tumor cell apoptosis >40% and arresting cell cycle at G2/M. TSE-BJO NEs could co-deliver drugs into the target cells efficiently and exhibit satisfying synergism. Besides, TSE-BJO NEs facilitated the long circulation of bufadienolides contributing to the high accumulation of drugs at tumor sites and the improvement of anti-tumor efficacy. The study achieves the combinative administration of the toxic TSE and BJO with high efficacy and safety.

Graphical Abstract

Keywords:

• Toad skin
• Brucea javanica oil
• nanoemulsions
• unification of drugs and excipients

Author contributions

Yan Ma contributed to the conception of the study. Quandong Li and Xinru Chen performed the experiments. Quandong Li and Xinru Chen contributed significantly to the analysis and manuscript preparation. Xinru Chen performed the data analyses and wrote the manuscript. Wen Lin and Xiaofeng Guo helped perform the analysis with constructive discussions.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Science and Technology Program of Guangzhou, P.R. China (grant numbers 201904010110).