Although the importance of quercetin (QUE) in diets and as food supplements is well-known, the oral utilization of QUE is limited by its instability, poor solubility, and low bioavailability. To overcome these disadvantages, QUE-loaded chitosan derivative-based nanoparticles (QUE-CDNPs) were fabricated, and their ameliorative efficacy against intestinal injury and gut microbiota dysbiosis in chemotherapy-induced mucositis were investigated. The morphology and structural characteristics of the QUE-CDNPs produced showed an average size of about 370.7 nm and a ζ potential of −21.9 mV. It indicated that the QUE encapsulation efficiency in CDNPs reached 71.2%, and the CDNP carrier substantially increased the bioavailability of QUE compared with that of the free QUE invivo. QUE-CDNP treatment remarkably alleviated the 5-Fu-induced destruction of villus and crypt in the jejunum. In addition, QUE-CDNPs effectively caused an attenuation of the pro-inflammation factors expression and an enhancement of claudin-1 expression in the jejunum, which consequently ameliorated intestinal barrier function. Furthermore, the QUE-CDNP treatment partially reversed the alterations in the intestinal microbiota of mice with 5-Fu-induced mucositis by decreasing the abundance of Bacteroides. These results demonstrate that the use of the QUE-CDNP-delivery system has the potential to improve both the stability and bioavailability and thus the efficacy of quercetin for the treatment of intestinal mucositis.

中文翻译：

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口服包裹壳聚糖衍生物的壳聚糖衍生物纳米颗粒减轻粘膜炎肠道损伤并调节肠道菌群失调。

尽管槲皮素（QUE）在饮食中和作为食品补充剂的重要性众所周知，但QUE的口服使用受到其不稳定，溶解性差和生物利用度低的限制。为了克服这些缺点，制备了基于QUE的壳聚糖衍生物纳米颗粒（QUE-CDNPs），并研究了它们在化疗诱导的粘膜炎中对肠损伤和肠道菌群失调的改善作用。所产生的QUE-CDNP的形态和结构特征显示出平均尺寸为约370.7nm，ζ电势为-21.9mV。这表明QUE在CDNPs中的包封效率达到了71.2％，并且CDNP载体与游离QUE在体内的生物利用度相比大大提高了QUE的生物利用度。。QUE-CDNP处理显着减轻了5-Fu诱导的空肠绒毛和隐窝破坏。另外，QUE-CDNPs有效地引起空肠中炎症因子的表达减弱和claudin-1表达的增强，从而改善了肠屏障功能。此外，QUE-CDNP处理通过降低拟杆菌的丰度，部分逆转了5-Fu致粘膜炎小鼠的肠道菌群变化。这些结果表明，QUE-CDNP-递送系统的使用具有改善稳定性和生物利用度以及因此槲皮素治疗肠粘膜炎的功效的潜力。