Yang Xi, Li Zhaojun, Wang Ning, Li Ling, Song Linjiang, He Tao, Sun Lu, Wang Zhihan, Wu Qinjie, Luo Na, Yi Cheng, Gong Changyang
Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China.
School of Medicine, Nankai University, Tianjin, 300071, China.
Sci Rep. 2015 May 18;5:10322. doi: 10.1038/srep10322.
To develop injectable formulation and improve the stability of curcumin (Cur), Cur was encapsulated into monomethyl poly (ethylene glycol)-poly (ε-caprolactone)-poly (trimethylene carbonate) (MPEG-P(CL-co-TMC)) micelles through a single-step solid dispersion method. The obtained Cur micelles had a small particle size of 27.6 ± 0.7 nm with polydisperse index (PDI) of 0.11 ± 0.05, drug loading of 14.07 ± 0.94%, and encapsulation efficiency of 96.08 ± 3.23%. Both free Cur and Cur micelles efficiently suppressed growth of CT26 colon carcinoma cells in vitro. The results of in vitro anticancer studies confirmed that apoptosis induction and cellular uptake on CT26 cells had completely increased in Cur micelles compared with free Cur. Besides, Cur micelles were more effective in suppressing the tumor growth of subcutaneous CT26 colon in vivo, and the mechanisms included the inhibition of tumor proliferation and angiogenesis and increased apoptosis of tumor cells. Furthermore, few side effects were found in Cur micelles. Overall, our findings suggested that Cur micelles could be a stabilized aqueous formulation for intravenous application with improved antitumor activity, which may be a potential treatment strategy for colon cancer in the future.
为了开发可注射制剂并提高姜黄素(Cur)的稳定性,通过单步固体分散法将Cur包裹于单甲氧基聚(乙二醇)-聚(ε-己内酯)-聚(三亚甲基碳酸酯)(MPEG-P(CL-co-TMC))胶束中。所制备的Cur胶束粒径小,为27.6±0.7nm,多分散指数(PDI)为0.11±0.05,载药量为14.07±0.94%,包封率为96.08±3.23%。游离Cur和Cur胶束在体外均能有效抑制CT26结肠癌细胞的生长。体外抗癌研究结果证实,与游离Cur相比,Cur胶束对CT26细胞的凋亡诱导作用和细胞摄取能力均显著增强。此外,Cur胶束在体内对皮下CT26结肠癌的肿瘤生长抑制作用更强,其机制包括抑制肿瘤增殖和血管生成以及增加肿瘤细胞凋亡。此外,Cur胶束的副作用较少。总体而言,我们的研究结果表明,Cur胶束可能是一种稳定的水性静脉注射制剂,具有增强的抗肿瘤活性,这可能是未来结肠癌的一种潜在治疗策略。