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姜黄素负载生物活性自纳米乳化制剂的开发、表征优化与评估及其对人乳腺癌MCF-7细胞的抑制作用

Development, Characterization Optimization, and Assessment of Curcumin-Loaded Bioactive Self-Nanoemulsifying Formulations and Their Inhibitory Effects on Human Breast Cancer MCF-7 Cells.

作者信息

Kazi Mohsin, A Nasr Fahd, Noman Omar, Alharbi Abdulrahman, Alqahtani Mohammed S, Alanazi Fars K

机构信息

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Medicinal Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

出版信息

Pharmaceutics. 2020 Nov 18;12(11):1107. doi: 10.3390/pharmaceutics12111107.

Abstract

Curcumin (CUR) is an attractive polyphenol for its anti-inflammatory, antibacterial, antioxidant, and anticancer properties. Poor solubility in water and sensitivity against sunlight are the most challenging characteristics in the development of CUR for clinical use. The aim is to develop oral lipid-based bioactive self-nanoemulsifying drug delivery systems (Bio-SNEDDSs) for curcumin as a candidate for cancer therapy. Bio-SNEDDSs containing black seed oil, medium-chain mono- and diglycerides, and surfactants were prepared as CUR delivery vehicles. The morphology, droplet size, physical stability, encapsulation efficiency, risk of precipitation, lipid digestion, antioxidant activity, and antimicrobial activity were evaluated for the representative formulations. Finally, an MTT assay was performed on MCF-7 cells to determine the cytotoxic effect of the different formulations. The results showed lower droplet size (28.53 nm) and higher drug-loading (CUR 20 mg, thymoquinone 1.2 mg) for the representative Bio-SNEDDS (black seed oil/Imwitor 988/KolliphorEL (35/15/50) % ), along with a transparent appearance upon aqueous dilution. The dynamic dispersion and in-vitro lipolysis data proved that the Bio-SNEDDS was able to keep the CUR in a solubilized form in the gastrointestinal tract. From the antioxidant and antimicrobial studies, it was suggested that the Bio-SNEDDS had the highest activity for disease control. The MTT assay showed that the representative Bio-SNEDDS treatment led to a reduction of cell viability of MCF-7 cells compared to pure CUR and conventional SNEDDSs. A Bio-SNEDDS with elevated entrapment efficiency, antioxidant/antimicrobial activities, and an antiproliferative effect could be the best anticancer drug candidate for potential oral delivery.

摘要

姜黄素(CUR)因其抗炎、抗菌、抗氧化和抗癌特性而成为一种有吸引力的多酚。水溶性差和对阳光敏感是姜黄素临床开发中最具挑战性的特性。目的是开发基于脂质的口服生物活性自纳米乳化药物递送系统(Bio-SNEDDSs),作为姜黄素用于癌症治疗的候选方案。制备了含有黑种草籽油、中链甘油单酯和甘油二酯以及表面活性剂的Bio-SNEDDSs作为姜黄素的递送载体。对代表性制剂的形态、液滴大小、物理稳定性、包封率、沉淀风险、脂质消化、抗氧化活性和抗菌活性进行了评估。最后,对MCF-7细胞进行MTT试验,以确定不同制剂的细胞毒性作用。结果表明,代表性的Bio-SNEDDS(黑种草籽油/Imwitor 988/聚氧乙烯蓖麻油(35/15/50)%)具有较低的液滴大小(28.53 nm)和较高的载药量(姜黄素20 mg,百里醌1.2 mg),加水稀释后外观透明。动态分散和体外脂解数据证明,Bio-SNEDDS能够使姜黄素在胃肠道中保持溶解状态。从抗氧化和抗菌研究中可以看出,Bio-SNEDDS在疾病控制方面具有最高的活性。MTT试验表明,与纯姜黄素和传统SNEDDSs相比,代表性的Bio-SNEDDS处理导致MCF-7细胞的细胞活力降低。一种具有提高的包封效率、抗氧化/抗菌活性和抗增殖作用的Bio-SNEDDS可能是潜在口服给药的最佳抗癌药物候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddff/7698745/9c7c1d6f86c7/pharmaceutics-12-01107-g001.jpg

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