Controlling postprandial glucose levels for diabetic patients is critical to achieve the tight glycemic control that decreases the risk for developing long-term micro- and macrovascular complications. Herein, we report a glucose-responsive oral insulin delivery system based on Fc receptor (FcRn)-targeted liposomes with glucose-sensitive hyaluronic acid (HA) shell for postprandial glycemic regulation. After oral administration, the HA shell can quickly detach in the presence of increasing intestinal glucose concentration due to the competitive binding of glucose with the phenylboronic acid groups conjugated with HA. The exposed Fc groups on the surface of liposomes then facilitate enhanced intestinal absorption in an FcRn-mediated transport pathway. In vivo studies on chemically-induced type 1 diabetic mice show this oral glucose-responsive delivery approach can effectively reduce postprandial blood glucose excursions. This work is the first demonstration of an oral insulin delivery system directly triggered by increasing postprandial glucose concentrations in the intestine to provide an on-demand insulin release with ease of administration.

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控制糖尿病患者的餐后血糖水平对于实现严格的血糖控制至关重要，血糖控制可降低发生长期微血管和大血管并发症的风险。在本文中，我们报告了一种基于Fc受体（FcRn）靶向脂质体的葡萄糖反应性口服胰岛素递送系统，其葡萄糖敏感的透明质酸（HA）壳用于餐后血糖调节。口服后，由于葡萄糖与与HA偶联的苯基硼酸基团的竞争性结合，在肠葡萄糖浓度增加的情况下，HA壳层会迅速脱落。然后，脂质体表面上暴露的Fc基团促进FcRn介导的转运途径中肠道吸收的增强。体内对化学诱导的1型糖尿病小鼠的研究表明，这种口服葡萄糖反应性给药方法可以有效减少餐后血糖波动。这项工作是口服胰岛素传递系统的首次演示，该系统可通过增加肠道中餐后葡萄糖浓度直接触发，以提供按需胰岛素释放并易于给药。

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