School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Department of Pharmacy, Xintai People's Hospital of Shandong, Xintai 271200, Shandong, China.
Int J Pharm. 2018 Dec 20;553(1-2):510-521. doi: 10.1016/j.ijpharm.2018.10.019. Epub 2018 Oct 9.
Paclitaxel (PTX), one of the most potent anticancer agents, has showed a remarkable activity against varieties of tumors. However, the bioavailability of PTX is quite low due to its poor aqueous solubility. Moreover, the emerging multidrug resistance (MDR) in cancer to PTX remains a major obstacle for successful chemotherapy. In order to address these problems, we developed self-assembly of biotinylated poly(ethylene glycol)-poly(curcumin) (Biotin-PEG-PCDA) for PTX delivery (termed as PTX-BPC NPs) with the application of mPEG-P(CL-co-LLA) as an emulsifier. The loading content and encapsulation efficiency of PTX were 13.2% and 92.0%, respectively. In vitro drug release study showed that PTX-BPC NPs could degrade rapidly and then release the PTX payload in a 10 mM glutathione (GSH) environment. Compared with free PTX, PTX-BPC NPs exhibited enhanced anticancer efficacy (IC, 17.28 µg/mL vs. 1.15 µg/mL). In addition, these biotin-modified nanoparticles could also significantly reverse PTX resistance by suppressing the over-expression of P-gp, thus resulting in increased intracellular drug accumulation and reduced drug efflux in MCF-7/ADR cells, which showed a great anticancer effect.
紫杉醇（PTX）是最有效的抗癌药物之一，对多种肿瘤表现出显著的活性。然而，由于其较差的水溶性，PTX 的生物利用度相当低。此外，癌症中新兴的多药耐药性（MDR）仍然是成功化疗的主要障碍。为了解决这些问题，我们开发了生物素化聚乙二醇-聚（姜黄素）（Biotin-PEG-PCDA）的自组装用于 PTX 传递（命名为 PTX-BPC NPs），应用 mPEG-P（CL-co-LLA）作为乳化剂。PTX 的载药量和包封效率分别为 13.2%和 92.0%。体外药物释放研究表明，PTX-BPC NPs 在 10 mM 谷胱甘肽（GSH）环境中可以快速降解，然后释放 PTX 有效载荷。与游离 PTX 相比，PTX-BPC NPs 表现出增强的抗癌功效（IC，17.28 µg/mL 对 1.15 µg/mL）。此外，这些生物素修饰的纳米颗粒还可以通过抑制 P-糖蛋白的过度表达来显著逆转 PTX 耐药性，从而导致 MCF-7/ADR 细胞内药物积累增加和药物外排减少，从而产生强大的抗癌作用。
