Glucose-responsive insulin delivery systems that mimic pancreatic endocrine function could enhance health and improve quality of life for people with type 1 and type 2 diabetes with reduced β-cell function. However, insulin delivery systems with rapid in vivo glucose-responsive behaviour typically have limited insulin-loading capacities and cannot be manufactured easily. Here, we show that a single removable transdermal patch, bearing microneedles loaded with insulin and a non-degradable glucose-responsive polymeric matrix, and fabricated via in situ photopolymerization, regulated blood glucose in insulin-deficient diabetic mice and minipigs (for minipigs >25 kg, glucose regulation lasted >20 h with patches of ~5 cm2). Under hyperglycaemic conditions, phenylboronic acid units within the polymeric matrix reversibly form glucose-boronate complexes that-owing to their increased negative charge-induce the swelling of the polymeric matrix and weaken the electrostatic interactions between the negatively charged insulin and polymers, promoting the rapid release of insulin. This proof-of-concept demonstration may aid the development of other translational stimuli-responsive microneedle patches for drug delivery.

中文翻译：

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葡萄糖反应性胰岛素贴剂，用于调节小鼠和小型猪的血糖。

模仿胰腺内分泌功能的葡萄糖反应性胰岛素递送系统可以增强β细胞功能降低的1型和2型糖尿病患者的健康，并改善他们的生活质量。然而，具有快速的体内葡萄糖响应行为的胰岛素递送系统通常具有有限的胰岛素负荷能力，并且不容易制造。在这里，我们显示了一个可移动的透皮贴片，装有微针，该微针装有胰岛素和不可降解的葡萄糖反应性聚合物基质，并通过原位光聚合制备，可调节胰岛素缺乏型糖尿病小鼠和小型猪的血糖（对于小型猪> 25千克，葡萄糖调节持续> 20 h，斑块约5 cm2）。在高血糖情况下，聚合物基质中的苯基硼酸单元可逆地形成葡萄糖-硼酸酯络合物，由于它们的负电荷增加，会导致聚合物基质溶胀并削弱带负电荷的胰岛素与聚合物之间的静电相互作用，从而促进胰岛素的快速释放。这一概念验证证明可能有助于开发其他翻译刺激反应性微针贴片以进行药物递送。