Department of Pharmaceutics, College of Pharmacy, Shandong University , Jinan , China and.
Drug Deliv. 2015 Jan;22(1):50-7. doi: 10.3109/10717544.2013.873501. Epub 2014 Jan 13.
Although curcumin (CUR) can inhibit proliferation and induce apoptosis of tumors, the poor water solubility restricted its clinical application. The aim of this study was to improve the aqueous solubility of CUR and make more favorable changes to bioactivity by preparing curcumin-loaded phospholipid-sodium deoxycholate-mixed micelles (CUR-PC-SDC-MMs). CUR-PC-SDC-MMs were prepared by the thin-film dispersion method. Based on the results of single factor exploration, the preparation technology was optimized using the central composite design-response surface methodology with drug loading and entrapment efficiency (EE%) as indicators. The images of transmission electron microscopy showed that the optimized CUR-PC-SDC-MMs were spherical and well dispersed. The average size of the mixed micelles was 66.5 nm, the zeta potential was about -26.96 mV and critical micelle concentration was 0.0087 g/l. CUR was encapsulated in PC-SDC-MMs with loading capacity of 13.12%, EE% of 87.58%, and the solubility of CUR in water was 3.14 mg/ml. The release results in vitro showed that the mixed micelles presented sustained release behavior compared to the propylene glycol solution of CUR. The IC50 values of CUR-loaded micelles and free drug in human breast carcinoma cell lines were 4.10 μg/ml and 6.93 µg/ml, respectively. It could be concluded from the above results that the CUR-PC-SDC-MMs system might serve as a promising nanocarrier to improve the solubility and bioactivity of CUR.
虽然姜黄素 (CUR) 可以抑制肿瘤的增殖并诱导其凋亡,但较差的水溶性限制了其在临床上的应用。本研究旨在通过制备载姜黄素的磷脂-脱氧胆酸钠混合胶束 (CUR-PC-SDC-MMs) 来提高 CUR 的水溶性并使其生物活性发生更有利的变化。CUR-PC-SDC-MMs 通过薄膜分散法制备。基于单因素探索的结果,采用中心复合设计-响应面法优化了载药率和包封率(EE%)作为指标的制备工艺。透射电子显微镜的图像表明,优化后的 CUR-PC-SDC-MMs 呈球形且分散良好。混合胶束的平均粒径为 66.5nm,Zeta 电位约为-26.96mV,临界胶束浓度为 0.0087g/l。CUR 被包封在 PC-SDC-MMs 中,载药量为 13.12%,EE%为 87.58%,在水中的溶解度为 3.14mg/ml。体外释放结果表明,与 CUR 的丙二醇溶液相比,混合胶束呈现出持续释放行为。载药胶束和游离药物在人乳腺癌细胞系中的 IC50 值分别为 4.10μg/ml 和 6.93μg/ml。从以上结果可以得出结论,CUR-PC-SDC-MMs 系统可能是一种有前途的纳米载体,可以提高 CUR 的溶解度和生物活性。