School of Pharmaceutical Sciences, Guangdong Medical University, Dongguan, 523808, People's Republic of China.
Dongguan Key Laboratory of Screening and Research of Anti-Inflammatory Ingredients in Chinese Medicine, Guangdong Medical University, Dongguan, 523808, People's Republic of China.
Int J Nanomedicine. 2024 Aug 22;19:8603-8620. doi: 10.2147/IJN.S472445. eCollection 2024.
Chemotherapeutic drugs have some drawbacks in antineoplastic therapy, mainly containing seriously toxic side effects caused by injection and multi-drug resistance (MDR). Co-delivery with two or more drugs via nanomicelles is a promising strategy to solve these problems. Oral chemotherapy is increasingly preferred owing to its potential to enhance the life quality of patients.
The study intended to develop mixed micelles using D-α-Tocopherol poly(ethylene glycol) 1000 succinate (TPGS) and soluplus for the co-encapsulation of docetaxel (DTX) and curcumin (CUR), marked as (DTX+CUR)-loaded mixed micelles, treating drug-resistant breast cancer by oral administration. The (DTX+CUR)-loaded mixed micelles had a uniform particle size (~64 nm), high drug loading and encapsulation efficiency, in vitro sustained-release properties and good pH-dependent stability. In vitro cell study, the (DTX+CUR)-loaded mixed micelles displayed the highest cellular uptake, cytotoxicity, cell apoptosis-inducing rates and cell ROS-inducing levels on MCF-7/Adr cells. Notably, in vivo pharmacokinetic studies, (DTX+CUR)-loaded mixed micelles enhanced markedly the oral absorption of DTX compared to pure DTX, with a relative oral bioavailability of 574%. The (DTX+CUR)-loaded mixed micelles by oral administration had the same anticancer efficacy as taxotere by injection in resistant breast cancer bearing mice.
(DTX+CUR)-loaded mixed micelles could provide a potential formulation for treating drug-resistant breast cancers by oral administration.
化疗药物在抗肿瘤治疗中有一些缺点，主要包括注射引起的严重毒性副作用和多药耐药性（MDR）。通过纳米胶束共递送两种或更多药物是解决这些问题的一种有前途的策略。口服化疗由于其提高患者生活质量的潜力而越来越受到青睐。
本研究旨在开发使用 D-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS）和 Soluplus 的混合胶束，共包封多西紫杉醇（DTX）和姜黄素（CUR），标记为（DTX+CUR）载药混合胶束，通过口服给药治疗耐药乳腺癌。（DTX+CUR）载药混合胶束具有均匀的粒径（~64nm）、高载药量和包封效率、体外缓释特性和良好的 pH 依赖性稳定性。体外细胞研究表明，（DTX+CUR）载药混合胶束对 MCF-7/Adr 细胞具有最高的细胞摄取、细胞毒性、细胞凋亡诱导率和细胞 ROS 诱导水平。值得注意的是，体内药代动力学研究表明，与纯 DTX 相比，（DTX+CUR）载药混合胶束显著增强了 DTX 的口服吸收，相对口服生物利用度为 574%。口服给予（DTX+CUR）载药混合胶束在耐药乳腺癌荷瘤小鼠中具有与注射用多西他赛相同的抗癌疗效。
（DTX+CUR）载药混合胶束可为口服治疗耐药乳腺癌提供一种有潜力的制剂。
