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用于结肠癌治疗的不同沸石系统:离子释放、细胞毒性及药物释放行为的监测

Different zeolite systems for colon cancer therapy: monitoring of ion release, cytotoxicity and drug release behavior.

作者信息

Abd-Elsatar A G, Farag M M, Youssef H F, Salih S A, Mounier M M, El-Meliegy E

机构信息

Ceramics, Refractories and Building Materials Department, National Research Centre, 33 El-Buhouth Street, Dokki, Cairo, 12622, Egypt.

Glass Research Department, National Research Centre, 33 El-Buhouth Street, Dokki, Cairo, 12622, Egypt.

出版信息

Prog Biomater. 2019 Jun;8(2):101-113. doi: 10.1007/s40204-019-0115-8. Epub 2019 May 20.

Abstract

Three types of oral administrated micronized zeolites [ZSM-5, zeolite A and Faujasite NaX (ZSM-5, ZA and ZX, respectively)] were prepared as anticancer 5-fluorouracil (5-Fu) delivery systems for colon cancer treatment. They were prepared by economically widespread and cheap natural resource, kaolin, at low temperatures, using microwave advanced tool. The obtained powders were characterized by XRD, SEM/EDX and BET; meanwhile, their degradation was investigated in two gastric fluids; FaSSGF (pH 1.6) and FeSSGF (pH 5), through concentration measurement of their solution disintegrated elemental constituents of Na, Al and Si ions. Also, the processes of drug release and mechanism in both solutions were investigated. Moreover, the inhibition action of 5-Fu-free and 5-Fu-conjugated zeolites on colon cancer cells (CaCo-2) was estimated. The results showed that, the prepared zeolites possessed high surface areas of 526, 250, and 578 m/g for ZSM-5, ZA and ZX, respectively. Although, zeolite structures seemed significantly stable, their frameworks seemed more likely reactive with time. The ions and drug release for zeolites occurred in successively two stages and found to be pH dependent, where the drug and zeolite ions were significantly of higher values in the more acidic media of the gastric solution (pH 1.6) than those of the mild acidic one (pH 5). The obtained activity indicated no cytotoxic affinity for all the prepared zeolite types. Accordingly, the synthesized zeolite frameworks are proposed to be of strong potential drug delivery vehicle for the treatment of gastrointestinal cancer.

摘要

制备了三种口服微粉化沸石[分别为ZSM - 5、A型沸石和八面沸石NaX(分别为ZSM - 5、ZA和ZX)]作为用于结肠癌治疗的抗癌5 - 氟尿嘧啶(5 - Fu)递送系统。它们是利用微波先进工具,在低温下通过经济上广泛且廉价的天然资源高岭土制备而成。通过X射线衍射(XRD)、扫描电子显微镜/能谱仪(SEM/EDX)和比表面积分析仪(BET)对所得粉末进行了表征;同时,通过测量其在两种胃液[模拟禁食状态下的胃液(FaSSGF,pH 1.6)和模拟进食状态下的胃液(FeSSGF,pH 5)]中崩解后溶液中钠、铝和硅离子等元素成分的浓度,研究了它们的降解情况。此外,还研究了两种溶液中的药物释放过程及机制。而且,评估了不含5 - Fu和负载5 - Fu的沸石对结肠癌细胞(CaCo - 2)的抑制作用。结果表明,制备的沸石比表面积分别为:ZSM - 5为526 m²/g、ZA为250 m²/g、ZX为578 m²/g。尽管沸石结构看起来相当稳定,但它们的骨架似乎随时间更易发生反应。沸石的离子和药物释放分两个连续阶段进行,且发现其与pH有关,在胃酸溶液酸性更强的介质(pH 1.6)中,药物和沸石离子的含量明显高于酸性较弱的介质(pH 5)中的含量。所获得的活性表明,所有制备的沸石类型均无细胞毒性亲和力。因此,所合成的沸石骨架被认为具有作为治疗胃肠道癌症的强大潜在药物递送载体的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c14/6556166/ad4437ba1f83/40204_2019_115_Fig1_HTML.jpg

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