Precision NanoSystems Inc , Vancouver , British Columbia V6P 6T7 , Canada.
Mol Pharm. 2019 Sep 3;16(9):3957-3967. doi: 10.1021/acs.molpharmaceut.9b00583. Epub 2019 Aug 16.
Curcumin exhibits potent anticancer activity via various mechanisms, but its in vivo efficacy has been hampered by poor solubility. Nanotechnology has been employed to deliver curcumin, but most of the reported systems suffered from low drug loading capacity and poor stability. Here, we report the development and optimization of a liposomal formulation for curcumin (Lipo-Cur) using an automated microfluidic technology. Lipo-Cur exhibited a mean diameter of 120 nm with a low polydispersity index (<0.2) and superior loading capacity (17 wt %) compared to other reported liposomal systems. Lipo-Cur increased the water solubility of curcumin by 700-fold, leading to 8-20-fold increased systemic exposure compared to the standard curcumin suspension formulation. When coadministered with cisplatin to tumor-bearing mice, Lipo-Cur augmented the antitumor efficacy of cisplatin in multiple mouse tumor models and decreased the nephrotoxicity. This is the first report demonstrating the dual effects of curcumin enabled by a nanoformulation in enhancing the efficacy and reducing the toxicity of a chemo-drug in animal models under a single and low dose administration.
姜黄素通过多种机制表现出强大的抗癌活性,但由于其溶解度差,其体内疗效受到阻碍。纳米技术已被用于递送姜黄素,但大多数报道的系统都存在载药量低和稳定性差的问题。在这里,我们报告了使用自动化微流控技术开发和优化姜黄素脂质体(Lipo-Cur)的制剂。与其他报道的脂质体系统相比,Lipo-Cur 表现出 120nm 的平均直径,低多分散指数(<0.2)和优越的载药量(17wt%)。Lipo-Cur 将姜黄素的水溶解度提高了 700 倍,与标准姜黄素混悬剂配方相比,系统暴露增加了 8-20 倍。当与顺铂一起给予荷瘤小鼠时,Lipo-Cur 在多种小鼠肿瘤模型中增强了顺铂的抗肿瘤疗效,并降低了顺铂的肾毒性。这是第一个报告,证明了纳米制剂使姜黄素具有双重作用,在单次和低剂量给药下,在动物模型中增强了化疗药物的疗效并降低了其毒性。