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一种新型亲水性抗肿瘤药物潜在载体的设计与评价:黑木耳多糖-壳聚糖纳米粒作为盐酸多柔比星的递送系统

Design and evaluation of a novel potential carrier for a hydrophilic antitumor drug: Auricularia auricular polysaccharide-chitosan nanoparticles as a delivery system for doxorubicin hydrochloride.

作者信息

Xiong Wei, Li Li, Wang Yingying, Yu Yibin, Wang Shenxia, Gao Yunyun, Liang Yanyao, Zhang Guogang, Pan Weisan, Yang Xinggang

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.

College of Information and Computer Engineering, Northeast Forestry University, 26 Hexing Street, Harbin 150040, China.

出版信息

Int J Pharm. 2016 Sep 10;511(1):267-275. doi: 10.1016/j.ijpharm.2016.07.026. Epub 2016 Jul 14.

Abstract

To improve the low loading content of hydrophilic drugs in nanodrug delivery systems, a natural watersoluble polysaccharide, Auricularia auricular polysaccharide (AAP), was extracted and purified as a vehicle for the hydrophilic drug doxorubicin hydrochloride (Dox·HCl). This involved the preparation of polyelectrolyte complexes nanoparticles (PEC NPs) using the electrostatic interaction between cationic chitosan (CS) and anionic AAP. The formation of AAP-CS-NPs was confirmed by FT-IR and TEM. It was found that Dox-loaded AAP-CS-NPs possessed a spherical morphology with average diameters of 237.6nm and 74.1% Dox·HCl encapsulation efficiency. The stability of Dox AAP-CS-NPs was examined by suspending the nanoparticles in PBS (pH 7.4) at room temperature. The particle size of the nanoparticle samples remained stable and exhibited no obvious variations in drug content after half a month. In addition, in vitro cytotoxicity studies showed that blank AAP-CS-NPs did not exhibit any cytotoxic effects, while Dox AAP-CS-NPs increased the Dox·HCl cytotoxicity against MCF-7 cells as the result of significantly increased cellular uptake, compared with free Dox·HCl. Hence, the overall results obtained suggest that AAP-CS-NPs are very effective in entrapping Dox·HCl and to penetrate into tumor cells, rendering them promising carriers for hydrophilic antitumor drugs.

摘要

为提高纳米药物递送系统中亲水性药物的低负载量,提取并纯化了一种天然水溶性多糖——黑木耳多糖(AAP),作为亲水性药物盐酸多柔比星(Dox·HCl)的载体。这包括利用阳离子壳聚糖(CS)与阴离子AAP之间的静电相互作用制备聚电解质复合物纳米颗粒(PEC NPs)。通过傅里叶变换红外光谱(FT-IR)和透射电子显微镜(TEM)证实了AAP-CS-NPs的形成。结果发现,负载Dox的AAP-CS-NPs呈球形,平均直径为237.6nm,盐酸多柔比星包封率为74.1%。通过将纳米颗粒悬浮于室温下的PBS(pH 7.4)中,考察了Dox AAP-CS-NPs的稳定性。半个月后,纳米颗粒样品的粒径保持稳定,药物含量无明显变化。此外,体外细胞毒性研究表明,空白AAP-CS-NPs未表现出任何细胞毒性作用,而Dox AAP-CS-NPs由于细胞摄取显著增加,增强了盐酸多柔比星对MCF-7细胞的细胞毒性,与游离盐酸多柔比星相比。因此,总体结果表明,AAP-CS-NPs在包封盐酸多柔比星并穿透肿瘤细胞方面非常有效,使其成为亲水性抗肿瘤药物的有前景的载体。

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