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用于姜黄素和黄连素共递送的玉米醇溶蛋白-壳聚糖纳米粒的制备、表征及体外细胞暴露研究

Fabrication, characterization and in vitro cell exposure study of zein-chitosan nanoparticles for co-delivery of curcumin and berberine.

作者信息

Ghobadi-Oghaz Niloofar, Asoodeh Ahmad, Mohammadi Marzieh

机构信息

Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran; Cellular and Molecular Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.

出版信息

Int J Biol Macromol. 2022 Apr 15;204:576-586. doi: 10.1016/j.ijbiomac.2022.02.041. Epub 2022 Feb 11.

Abstract

For the first time, we synthesized the co-delivery nanopolymers using zein protein as the core and chitosan polysaccharide as the shell to deliver curcumin (Cur) and berberine (Ber) in MDA-MB-231 breast cancer cells. It has been shown that Cur and Ber altogether have synergistic effects on multiple cancers. Herein, the curcumin-zein-berberine-chitosan (Cur-Z-Ber-Ch) nanoparticles were fabricated and their organization procedure was reported. Physicochemical properties of synthesized nanoparticles were determined by Fourier transform infrared (FTIR) spectroscopy, XRD and fluorescence spectroscopy analyses. The nanoparticles included relatively small particles (d = 168.24 nm) with +36.76 mV zeta potential. The resulting nanoparticles had high entrapment efficiency (about 75%) for Cur and 60% for Ber. The Cur-Z-Ber-Ch nanoparticles represented ideal redispersibility and storage stability after 4 months. Drug release of the freeze-dried nanoparticles had pH-sensitive characteristic. In vitro cytoxicity assay demonstrated that Cur-Z-Ber-Ch nanoparticles induced elevated cytotoxic effect in MDA-MB-231 and A549 cancer cells. In vitro studies in MDA-MB-231 cells demonstrated that the Cur-Z-Ber-Ch nanoparticles could successfully increase cellular uptake and apoptosis with significant inhibition of IL-8 pro-inflammatory cytokines in comparison to the free Cur + Ber bioactive molecules. These bio-nanoparticles are the co-delivery vehicle for Cur and Ber which could be beneficial for participating them into pharmaceutical products.

摘要

我们首次合成了以玉米醇溶蛋白为核心、壳聚糖多糖为外壳的共递送纳米聚合物,用于在MDA-MB-231乳腺癌细胞中递送姜黄素(Cur)和黄连素(Ber)。研究表明,Cur和Ber对多种癌症具有协同作用。在此,制备了姜黄素-玉米醇溶蛋白-黄连素-壳聚糖(Cur-Z-Ber-Ch)纳米颗粒并报道了其制备过程。通过傅里叶变换红外(FTIR)光谱、XRD和荧光光谱分析确定了合成纳米颗粒的物理化学性质。纳米颗粒包括相对较小的颗粒(d = 168.24 nm),ζ电位为+36.76 mV。所得纳米颗粒对Cur的包封率较高(约75%),对Ber的包封率为60%。Cur-Z-Ber-Ch纳米颗粒在4个月后表现出理想的再分散性和储存稳定性。冻干纳米颗粒的药物释放具有pH敏感特性。体外细胞毒性试验表明,Cur-Z-Ber-Ch纳米颗粒在MDA-MB-231和A549癌细胞中诱导了更高的细胞毒性作用。在MDA-MB-231细胞中的体外研究表明,与游离的Cur + Ber生物活性分子相比,Cur-Z-Ber-Ch纳米颗粒能够成功增加细胞摄取和凋亡,并显著抑制IL-8促炎细胞因子。这些生物纳米颗粒是Cur和Ber的共递送载体,可能有利于将它们应用于药物产品中。

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