Intestine-Settled Electrospun Short-Fibers Modulate Epithelial Transport Proteins to Reduce Purine and Glucose Uptake

IF 17.2 1区 工程技术 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Yunkai Tang, Juan Wang, Zhengwei Cai, Bruno Sarmento, Yawei Du, Wenguo Cui
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Abstract

Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia, mediated by specific intestinal transport proteins. Currently, there is a deficiency in targeted regulation of these proteins. In this study, we introduce an oral approach for targeted modulation using electrospun core–shell short-fibers that settle on the intestinal mucosa. These fibers, designed for the controlled in situ release of phlorizin—a multi-transporter inhibitor—are crafted through a refined electrospinning-homogenizing process using polylactic acid and gelatin. Phlorizin is conjugated via a phenyl borate ester bond. Furthermore, a calcium alginate shell ensures intestinal disintegration triggered by pH changes. These fibers adhere to the mucosa due to their unique structure, and phlorizin is released in situ post-ingestion through glucose-sensitive cleavage of the phenyl borate ester bond, enabling dual-target inhibition of intestinal transporter proteins. Both in vitro and in vivo studies confirm that the short-fibers possess intestine-settling and glucose-responsive properties, facilitating precise control over transport proteins. Using models of hyperuricemia and diabetes in mice, treatment with short-fibers results in reductions of 49.6% in blood uric acid and 17.8% in glucose levels, respectively. Additionally, 16S rRNA sequencing indicates an improved intestinal flora composition. In conclusion, we have developed an innovative oral strategy for the prevention of hyperglycemia and hyperuricemia.

Graphical abstract

Abstract Image

肠道沉降电纺短纤维调节上皮转运蛋白以减少嘌呤和葡萄糖的吸收
嘌呤和葡萄糖摄入过多会导致高血糖和高尿酸血症,这是由特定的肠道转运蛋白介导的。目前,对这些蛋白的靶向调节还存在不足。在这项研究中,我们介绍了一种利用电纺芯壳短纤维在肠粘膜上沉积进行定向调节的口服方法。这些纤维是利用聚乳酸和明胶通过精细的电纺丝均质工艺制成的,用于控制多转运体抑制剂--氯嗪的原位释放。氯嗪通过苯基硼酸酯键共轭。此外,海藻酸钙外壳可确保在 pH 值变化时引发肠道崩解。这些纤维因其独特的结构而粘附在粘膜上,通过葡萄糖敏感的苯硼酸酯键裂解作用,氯嗪在摄入后就地释放,从而实现对肠道转运蛋白的双靶点抑制。体外和体内研究都证实,短纤维具有肠道稳定和葡萄糖反应特性,有助于精确控制转运蛋白。利用小鼠高尿酸血症和糖尿病模型,使用短纤维治疗后,血尿酸和血糖水平分别降低了 49.6% 和 17.8%。此外,16S rRNA 测序表明肠道菌群组成得到改善。总之,我们开发出了一种预防高血糖和高尿酸血症的创新口服策略。 图文摘要
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来源期刊
CiteScore
18.70
自引率
11.20%
发文量
109
期刊介绍: Advanced Fiber Materials is a hybrid, peer-reviewed, international and interdisciplinary research journal which aims to publish the most important papers in fibers and fiber-related devices as well as their applications.Indexed by SCIE, EI, Scopus et al. Publishing on fiber or fiber-related materials, technology, engineering and application.
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