智能口服胰岛素装置具有改善血糖管理的潜力。它可以降低与外源性胰岛素（INS）治疗相关的低血糖风险，同时还可以避免与皮下注射相关的许多缺点。此外，糖尿病（DM）是一种以炎症为特征的内分泌疾病，在维持平均血糖的同时最大限度地减少糖尿病患者炎症标志物的数量至关重要。在这项研究中，开发了一种具有抗炎作用的响应性纳米系统维生素 B12-岩藻多糖-刀豆球蛋白 A (VB12-FU-ConA NP)，用于智能口服胰岛素。 Con A作为葡萄糖响应材料具有高灵敏度和强特异性。褐藻糖胶具有抗炎、免疫调节和降血糖的功能，它可以与Con A结合形成可逆的复合物。在高葡萄糖条件下，游离葡萄糖竞争性地与刀豆蛋白 A 结合，从而使纳米载体膨胀并促进胰岛素释放。此外，在胃肠道的低pH环境下，带正电荷的VB12与阴离子岩藻依聚糖紧密结合，保护包裹在载体中的胰岛素，并且VB12还可以与肠上皮因子结合，提高转运率，从而促进INS吸收。体外测试表明，纳米颗粒在高血糖溶液中的释放明显高于正常血糖条件下的药物释放。在体内药效学过程中，口服纳米系统可显着降低 I 型糖尿病小鼠 (T1DM) 的血糖水平，从而最大限度地降低低血糖风险。 8小时后血糖水平达到最低8.1±0.4mmol/L。口服纳米系统可显着降低糖尿病小鼠血清中肿瘤坏死因子-α (TNF-α) 和白细胞介素 6 (IL-6) 的水平。该纳米递送系统口服后可在肠道内降解代谢，具有良好的生物降解性和生物安全性。总之，本研究表明 VB12-FU-ConA 纳米载体有望成为一种合理化血糖的新型系统。版权所有 © 2024。由 Elsevier B.V. 出版。

The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose.Copyright © 2024. Published by Elsevier B.V.