β-Elemene-loaded polymeric micelles intensify anti-carcinoma efficacy and alleviate side effects

Abstract β-Elemene is a volatile oil used for the treatment of cancer, but poor solubility, low bioavailability, and various adverse reactions limit its application. For ameliorating risks of the venous toxicity of β-elemene, intravenously injectable micelle of β-elemene was prepared using the thin-film hydration method. The results pointed out the micellar was uniformly spherical with about 20.96 ± 0.1966 nm in average diameter and exhibited high entrapment efficiency (99.02% ± 0.88%). As revealed by drug release studies in vitro, β-elemene micelles had sustained drug release. Compared with free β-elemene, the micelles increased the drug cellular uptake and enhanced anti-tumor effect in vitro through retarding cell cycle and inducing apoptosis. Meanwhile, the elevated serum stability of β-elemene micelles implied less drug leakage and reduced toxicity. The wound healing and tube formation assay in vitro manifested anti-metastasis and anti-angiogenesis effects of β-elemene micelles. Moreover, the pharmacokinetics study showed the AUC and T1/2 of β-elemene in micelle group was 1.79 and 1.62 times of that in the free β-elemene group, suggesting the circulation time of β-elemene in the blood had been prolonged. In addition, β-elemene micelles showed a favorable antitumor response compared with the β-elemene solution on the C26 colon cancer-bearing mice model. Local irritation study investigated in rabbits indicated that the β-elemene micelles strikingly mitigated the irritation to the injection sites compared with free β-elemene. These results have been proved that the micelle could be a good candidate as an auspicious drug delivery system of β-elemene for the prospective clinical treatment of carcinoma.