State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Int J Pharm. 2013 Feb 25;443(1-2):175-82. doi: 10.1016/j.ijpharm.2012.12.032. Epub 2012 Dec 31.
This work aims to develop curcumin (Cur) loaded biodegradable self-assembled polymeric micelles (Cur-M) to overcome poor water solubility of Cur and to meet the requirement of intravenous administration. Cur-M were prepared by solid dispersion method, which was simple and easy to scale up. Cur-M had a small particle size of 28.2 ± 1.8 nm and polydisperse index (PDI) of 0.136 ± 0.050, and drug loading and encapsulation efficiency of Cur-M were 14.84 ± 0.11% and 98.91 ± 0.70%, respectively. Besides, in vitro release profile showed a significant difference between rapid release of free Cur and much slower and sustained release of Cur-M. Cytotoxicity study showed that the encapsulated Cur remained its potent anti-tumor effect. Furthermore, Cur-M were more effective in inhibiting tumor growth and spontaneous pulmonary metastasis in subcutaneous 4T1 breast tumor model, and prolonged survival of tumor-bearing mice. In addition, immunofluorescent and immunohistochemical studies also showed that tumors of Cur-M-treated mice had more apoptosis cells, fewer microvessels, and fewer proliferation-positive cells. In conclusion, polymeric micelles encapsulating Cur were developed with enhanced anti-tumor and anti-metastasis activity on breast tumor, and Cur-M is excellent water-based formulation of Cur which may serve as a candidate for breast cancer therapy.
本研究旨在开发负载姜黄素(Cur)的可生物降解自组装聚合物胶束(Cur-M),以克服 Cur 的低水溶性并满足静脉给药的要求。Cur-M 采用固体分散法制备,方法简单,易于放大。Cur-M 的粒径为 28.2±1.8nm,多分散指数(PDI)为 0.136±0.050,载药量和包封率分别为 14.84±0.11%和 98.91±0.70%。此外,体外释放曲线显示游离 Cur 的快速释放与 Cur-M 的缓慢持续释放之间存在显著差异。细胞毒性研究表明,包封的 Cur 保持了其强大的抗肿瘤作用。此外,Cur-M 在皮下 4T1 乳腺癌模型中更有效地抑制肿瘤生长和自发性肺转移,并延长荷瘤小鼠的生存时间。此外,免疫荧光和免疫组织化学研究还表明,Cur-M 治疗组的肿瘤具有更多的凋亡细胞、更少的微血管和更少的增殖阳性细胞。总之,开发了负载姜黄素的聚合物胶束,对乳腺癌具有增强的抗肿瘤和抗转移活性,Cur-M 是 Cur 的优良水基制剂,可能成为乳腺癌治疗的候选药物。