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新型 pH 驱动载体的研制:海藻酸钠/羧甲基淀粉生物涂层共载药@COF-OH 用于结肠癌的控释和协同治疗。

Development of the new pH-driven carrier from alginate/carboxymethyl starch bio-coated co-drugs@COF-OH for controlled and concomitant colon cancer treatment.

机构信息

Polymer Research Laboratory, Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.

Polymer Research Laboratory, Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Science, Tabriz, Iran.

出版信息

Int J Biol Macromol. 2023 Jun 1;239:124322. doi: 10.1016/j.ijbiomac.2023.124322. Epub 2023 Apr 3.

Abstract

To develop a new more efficient colon cancer treatment bio-vehicle, in frontier research, for the first time, an attempt has been made to design a unique colon-targeted bio-carrier containing polysaccharides along with nanoporous materials. So, at first, an imine-based covalent organic framework (COF-OH) with respectively an average pore diameter and surface area at 8.5058 nm and 208.29 m·g was fabricated. In the next step, about 41.68 % and 95.8 % of 5-fluorouracil (5-Fu) and curcumin (CUR) respectively were loaded on COF-OH, and 5-Fu + CUR@COF-OH was achieved. Due to the higher rate of drug releases in simulated stomach media, 5-Fu + CUR@COF-OH was coated with a mixture of alginate (Alg) and carboxymethyl starch (CMS) via the ionic crosslinking (Alg/CMS@(5-Fu + CUR@COF-OH)). Findings displayed that the use of polysaccharide coat reduce the drug releases in simulated gastric and improved it in simulated intestinal and colonic fluids. The beads swelled about 93.33 % under simulated gastrointestinal conditions, but this value was found higher in the simulated colonic environment and reached 326.67 %. The hemolysis rate lower than 5 %, as well as the cell viability higher than 80 %, were the main showing signs of system biocompatibility. Altogether, the results of the preliminary investigations can highlight the potential of the Alg/CMS@(5-Fu + CUR@COF-OH) for colon-specific drug delivery.

摘要

为了开发一种新的更有效的结肠癌治疗生物载体,在前沿研究中,首次尝试设计一种含有多糖和纳米多孔材料的独特的结肠靶向生物载体。因此,首先制备了一种基于亚胺的共价有机骨架(COF-OH),其平均孔径和比表面积分别为 8.5058nm 和 208.29m·g。下一步,分别将约 41.68%和 95.8%的 5-氟尿嘧啶(5-Fu)和姜黄素(CUR)负载在 COF-OH 上,得到 5-Fu+CUR@COF-OH。由于在模拟胃介质中的药物释放率较高,因此通过离子交联(Alg/CMS@(5-Fu+CUR@COF-OH))用藻酸盐(Alg)和羧甲基淀粉(CMS)的混合物对 5-Fu+CUR@COF-OH 进行包被。研究结果表明,多糖涂层的使用减少了模拟胃中的药物释放,并改善了模拟肠和结肠液中的药物释放。在模拟胃肠道条件下,微球膨胀约 93.33%,但在模拟结肠环境下,这一数值更高,达到 326.67%。溶血率低于 5%,细胞活力高于 80%,是系统生物相容性的主要表现标志。总之,初步研究结果可以突出 Alg/CMS@(5-Fu+CUR@COF-OH)在结肠特异性药物输送中的潜力。

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