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.
Keywords: Brucea javanica oil; Toad skin; nanoemulsions; unification of drugs and excipients.