International Journal of Nanomedicine (Aug 2024)
Co-Delivery of Docetaxel and Curcumin Functionalized Mixed Micelles for the Treatment of Drug-Resistant Breast Cancer by Oral Administration
Abstract
Chengyang Dian,1 Zebin Qian,1 Mengnan Ran,1 Xiong Yan,1 Linghui Dian1,2 1School of Pharmaceutical Sciences, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 2Dongguan Key Laboratory of Screening and Research of Anti-Inflammatory Ingredients in Chinese Medicine, Guangdong Medical University, Dongguan, 523808, People’s Republic of ChinaCorrespondence: Linghui Dian, School of Pharmaceutical Sciences, Guangdong Medical University, Xincheng Road 1, Dongguan, 523808, People’s Republic of China, Tel/Fax +86769 22896560, Email [email protected]: 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.Methods and Results: 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.Conclusion: (DTX+CUR)-loaded mixed micelles could provide a potential formulation for treating drug-resistant breast cancers by oral administration. Keywords: docetaxel, mixed micelles, resistant breast cancer, oral delivery, bioavailability, mice
