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载姜黄素聚合物胶束抑制乳腺肿瘤生长和自发性肺转移。

Curcumin loaded polymeric micelles inhibit breast tumor growth and spontaneous pulmonary metastasis.

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.

出版信息

Int J Pharm. 2013 Feb 25;443(1-2):175-82. doi: 10.1016/j.ijpharm.2012.12.032. Epub 2012 Dec 31.

Abstract

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.

摘要

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。

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