Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing 210028, China.
Jiangsu Provincial Academy of Traditional Chinese Medicine , Nanjing 210028, China.
Biomacromolecules. 2017 Apr 10;18(4):1268-1280. doi: 10.1021/acs.biomac.7b00011. Epub 2017 Mar 28.
The aim of this study is to demonstrate the enhanced therapeutic efficacy of anticancer drugs on drug-resistant breast cancer using multicomponent microemulsions (ECG-MEs) as an oral delivery system. The etoposide-loaded ECG-MEs were composed of coix seed oil and ginsenoside Rh2 (G-Rh2), both of which possess not only the synergistic antitumor effect with etoposide, but also have excipient-like properties. Orally administrated ECG-MEs were demonstrated to be able to accumulate at the tumor site following crossing the intestines as intact vehicles into the blood circulation. The spatiotemporal controlled release characteristics of ECG-MEs brought about the efficient P-gp inhibition by the initially released G-Rh2 and the increased intracellular accumulation of the sequentially released etoposide. The combination antitumor activity of etoposide, G-Rh2 and coix seed oil using ECG-MEs was verified on the xenograft drug-resistant breast tumor mouse models. In addition, the safety evaluation studies indicated that treatment with ECG-MEs did not cause any significant toxicity in vivo. These findings suggest that ECG-MEs as an oral formulation may offer a promising strategy to treat the drug-resistant breast cancer.
本研究旨在展示多组分微乳液（ECG-MEs）作为口服给药系统用于增强耐药乳腺癌的抗癌药物治疗效果。载依托泊苷的 ECG-MEs 由薏苡仁油和人参皂苷 Rh2（G-Rh2）组成，它们不仅具有与依托泊苷协同的抗肿瘤作用，而且具有赋形剂样特性。口服给予 ECG-MEs 后，能够作为完整载体穿过肠道进入血液循环并在肿瘤部位聚集。ECG-MEs 的时空调控释放特性导致最初释放的 G-Rh2 有效抑制 P-gp，随后释放的依托泊苷在细胞内积累增加。在异种耐药乳腺癌小鼠模型上验证了 ECG-MEs 中依托泊苷、G-Rh2 和薏苡仁油的联合抗肿瘤活性。此外，安全性评估研究表明，ECG-MEs 治疗在体内不会引起任何显著毒性。这些发现表明，ECG-MEs 作为一种口服制剂可能为治疗耐药乳腺癌提供一种有前途的策略。
