化疗药物在抗肿瘤治疗中存在一定的弊端，主要是注射引起的严重毒副作用和多重耐药性(MDR)。通过纳米胶束共同递送两种或多种药物是解决这些问题的一种有前景的策略。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。该研究旨在开发使用 D-α-生育酚聚乙二醇 1000 琥珀酸酯 (TPGS) 和 soluplus 的混合胶束，用于共封装多西他赛 ( DTX）和姜黄素（CUR），标记为负载（DTX CUR）的混合胶束，通过口服治疗耐药乳腺癌。负载(DTX CUR)的混合胶束具有均匀的粒径(~64 nm)、较高的载药量和包封率、体外缓释特性和良好的pH依赖性稳定性。在体外细胞研究中，负载 (DTX CUR) 的混合胶束在 MCF-7/Adr 细胞上表现出最高的细胞摄取、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，负载 (DTX CUR) 的混合胶束显着增强了 DTX 的口服吸收，相对口服生物利用度为 574%。口服(DTX CUR)负载混合胶束对耐药乳腺癌小鼠具有与注射泰素帝相同的抗癌功效。(DTX CUR)负载混合胶束可以为口服治疗耐药乳腺癌提供潜在的制剂。 © 2024 Dian 等人。

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.© 2024 Dian et al.