期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 589, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2020.119875
关键词
Paclitaxel; Curcumin; Polymeric nanoparticles; PCL-PEG-PCL; Breast cancer
资金
- Open Project Program of Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province
- Union Project of Luzhou Municipal People's Government-Southwest Medical University [2018LZXNYD-ZKO6]
- Affiliated hospital of Southwest Medical University [2017 -PT-28]
- Youth Fund Project of Southwest Medical University [2016-ZRQN-116, 2019-ZQN-169]
Multi-drug chemotherapy has been one of the most popular strategies for the treatment of malignant tumors, and has achieved desirable therapeutic outcomes. The objective of the present study is to develop biodegradable PCEC nanoparticles (NPs) for the co-delivery of paclitaxel (PTX) and curcumin (CUR), and investigate the antitumor effect of the drug delivery system (DDS: PTX-CUR-NPs) against breast cancer both in vitro and in vivo. The prepared PTX-CUR-NPs had a small size of 27.97 +/- 1.87 nm with a low polydispersity index (PDI, 0.197 +/- 0.040). The results exhibited slow release of PTX and CUR from the DDS without any burst effect. Further, the PTX-CUR-NPs displayed a dose-dependent cytotoxicity in MCF-7 cells with a higher apoptosis rate (64.29% +/- 1.97%) as compared to that of free drugs (PTX + CUR, 34.21% +/- 0.81%). The cellular uptake study revealed that the drug loaded PCEC polymeric nanoparticles were more readily uptaken by tumor cells in vitro. To evaluate the in vivo anti-tumor effect, the PTX-CUR-NPs were intravenously administered to BALB/c nude mouse xenografted with MCF-7 cells and the results exhibited significant inhibition of tumor growth with prolonged survival time and reduced side effect when compared with free drugs (PTX + CUR). Moreover, the administration of PTX-CUR-NPs treatment led to lower Ki67 expression (p < 0.05), and enhanced TUNEL positivity (higher apoptosis, p < 0.01) in tumor cells as compared to other treatment groups, suggesting the therapeutic efficacy of the DDS. Altogether, the present study suggests that the DDS PTX-CUR-NPs could be employed for the effective treatment of breast cancers in near future.
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