Li Lan, Ni Jingyu, Li Min, Chen Jingrui, Han Lifeng, Zhu Yan, Kong Deling, Mao Jingyuan, Wang Yi, Zhang Boli, Zhu Meifeng, Gao Xiumei, Fan Guanwei
a First Teaching Hospital of Tianjin University of Traditional Chinese Medicine , Tianjin , PR China.
b State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , Tianjin , PR China.
Drug Deliv. 2017 Nov;24(1):1617-1630. doi: 10.1080/10717544.2017.1391893.
Doxorubicin (DOX) is one of the most effective chemotherapy agents used in the treatment of hematological and solid tumors, however, it causes dose-related cardiotoxicity that may lead to heart failure in patients. One of the major reasons was increased reactive oxygen species (ROS) production. Ginsenoside Rg3 (Rg3), was powerful free radical scavengers and possessed cardioprotective effects. Nevertheless, Rg3 has low aqueous solubility and oral bioavailability, limiting its effects. Herein, we encapsulated Rg3 through spontaneous self-assembly of Pluronic F127 to improve its solubility and oral bioavailability. Moreover, co-administering Rg3 in Pluronic F127 micelles with doxorubicin can mitigate the cardiotoxicity, with ameliorating mitochondrial and metabolic function, improving calcium handling, and decreasing ROS production. In addition, it can improve the anticancer efficacy of doxorubicin. Therefore, our study provides a rational strategy for further developing a potentially viable adjunct-supportive treatment for reducing toxicity and increasing efficiency on chemotherapy.
阿霉素（DOX）是用于治疗血液系统肿瘤和实体瘤的最有效化疗药物之一，然而，它会引起与剂量相关的心脏毒性，这可能导致患者出现心力衰竭。主要原因之一是活性氧（ROS）生成增加。人参皂苷Rg3（Rg3）是强大的自由基清除剂，具有心脏保护作用。然而，Rg3的水溶性和口服生物利用度较低，限制了其效果。在此，我们通过普朗尼克F127的自发自组装来包裹Rg3，以提高其溶解度和口服生物利用度。此外，将Rg3与阿霉素共同给药于普朗尼克F127胶束中可减轻心脏毒性，改善线粒体和代谢功能，改善钙处理，并减少ROS生成。此外，它还可提高阿霉素的抗癌疗效。因此，我们的研究为进一步开发一种潜在可行的辅助支持治疗方法提供了合理策略，以降低化疗毒性并提高化疗效率。
