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ROS/pH 双重响应槲皮素负载鸟嘌呤硼酸超分子水凝胶灌肠剂治疗葡聚糖硫酸钠诱导的小鼠结肠炎。

ROS/pH dual-responsive quercetin-loaded guanosine borate supramolecular hydrogel enema in dextran sulfate sodium-induced colitis in mice.

机构信息

Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23, Back Street, Art Museum, Dongcheng District, Beijing 100010, China.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, No. 15 Beisanhuan Road East, Chaoyang District, Beijing 100029, China.

出版信息

J Mater Chem B. 2024 Oct 30;12(42):10861-10876. doi: 10.1039/d4tb01659a.

Abstract

Ulcerative colitis (UC) is an inflammatory bowel disease that predominantly impacts the colon, typically starting in the rectum. A significant characteristic of UC is its propensity to affect the distal colon, which is particularly beneficial for targeted treatments such as enemas. This localized approach ensures that the medication is delivered directly to the affected areas, resulting in minimal systemic absorption. In this research, we have formulated a novel stimuli-responsive quercetin-loaded guanosine borate supramolecular hydrogel (named GBQ hydrogel), designed to prolong the residence time of the drug and protect the ulcerated intestinal tissues. The GBQ hydrogel has exhibited excellent injectability, self-healing capabilities, and biocompatibility, rendering it an ideal candidate for enema administration. studies have highlighted its ROS/pH dual-responsive release profile, which mimics the microenvironment of intestinal inflammation. Furthermore, we assessed the efficacy of the GBQ hydrogel on dextran sulfate sodium (DSS)-induced colitis, a common animal model for UC. Our findings indicate that the GBQ hydrogel significantly reduces disease activity, mitigates oxidative stress, restores the intestinal mucosal barrier, and prevents colonic cell apoptosis. Collectively, this study underscores the therapeutic potential of the GBQ hydrogel in managing inflammatory bowel conditions and paves the way for a novel hydrogel enema-based treatment strategy for UC.

摘要

溃疡性结肠炎(UC)是一种炎症性肠病,主要影响结肠,通常从直肠开始。UC 的一个显著特征是其倾向于影响远端结肠,这对于靶向治疗如灌肠特别有益。这种局部方法确保药物直接输送到受影响的区域,从而最大限度地减少全身吸收。在这项研究中,我们设计了一种新型的刺激响应性槲皮素负载鸟苷硼酸超分子水凝胶(命名为 GBQ 水凝胶),旨在延长药物的停留时间并保护溃疡性肠组织。GBQ 水凝胶具有优异的可注射性、自修复能力和生物相容性,使其成为灌肠给药的理想候选物。研究强调了其 ROS/pH 双重响应释放特性,该特性模拟了肠道炎症的微环境。此外,我们评估了 GBQ 水凝胶在葡聚糖硫酸钠(DSS)诱导的结肠炎中的疗效,DSS 诱导的结肠炎是 UC 的一种常见动物模型。我们的研究结果表明,GBQ 水凝胶可显著降低疾病活动度,减轻氧化应激,恢复肠道黏膜屏障,并防止结肠细胞凋亡。总之,这项研究强调了 GBQ 水凝胶在管理炎症性肠病方面的治疗潜力,并为 UC 的新型水凝胶灌肠治疗策略铺平了道路。

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