State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
Nanoscale. 2011 Apr;3(4):1558-67. doi: 10.1039/c0nr00758g. Epub 2011 Jan 31.
Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 ± 0.011) with a mean particle size of 27.3 ± 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 ± 1.02%, and drug loading of 12.95 ± 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t(1/2) and AUC of curcumin in vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesis in vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cells in vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg(-1) curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.
姜黄素是一种有效的、安全的抗癌药物，但由于其疏水性，限制了其在临床上的应用。纳米技术为提高疏水性药物的水溶性提供了有效的方法。在这项工作中，通过一步纳米沉淀法将姜黄素包封到单甲氧基聚乙二醇-聚（ε-己内酯）（MPEG-PCL）胶束中，制备了载姜黄素的 MPEG-PCL（Cur/MPEG-PCL）胶束。这些 Cur/MPEG-PCL 胶束单分散性良好（PDI=0.097±0.011），平均粒径为 27.3±1.3nm，冻干后具有良好的再溶解性，包封效率为 99.16±1.02%，载药量为 12.95±0.15%。此外，这些胶束是通过一种简单、可重复的方法制备的，因此具有潜在的放大生产的可能。姜黄素分子分散在 MPEG-PCL 胶束的 PCL 核中，可以在体外缓慢释放。姜黄素包封在 MPEG-PCL 胶束中，提高了体内姜黄素的 t（1/2）和 AUC。与游离姜黄素一样，Cur/MPEG-PCL 胶束能有效抑制转基因斑马鱼模型的血管生成。在藻酸盐包被的癌细胞试验中，静脉注射 Cur/MPEG-PCL 胶束比游离姜黄素更有效地抑制了体内肿瘤细胞诱导的血管生成。MPEG-PCL 胶束包封的姜黄素在体外保持了姜黄素对 C-26 结肠癌细胞的细胞毒性。静脉注射 Cur/MPEG-PCL 胶束（25mgkg(-1)姜黄素）抑制了体内皮下 C-26 结肠癌细胞的生长（p<0.01），并诱导了比游离姜黄素更强的抗癌作用（p<0.05）。总之，Cur/MPEG-PCL 胶束是一种优秀的静脉注射用姜黄素水体制剂；该制剂通过抑制血管生成和直接杀伤癌细胞，抑制结肠癌的生长。
