Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs
Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs
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DOI：
10.1038/s41551-019-0508-y
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发表时间：
2020-02-03
影响因子：
28.1
通讯作者：
Gu, Zhen
中科院分区：
文献类型：
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作者：
Yu, Jicheng;Wang, Jinqiang;Gu, Zhen
模拟胰腺内分泌功能的葡萄糖反应性胰岛素输送系统可以改善β细胞功能降低的1型和2型糖尿病患者的健康和生活质量。然而，具有快速体内葡萄糖反应行为的胰岛素输送系统通常具有有限的胰岛素负荷能力，并且不易制造。在这里，我们展示了一个可拆卸的透皮贴片，上面有装载胰岛素的微针和不可降解的葡萄糖反应聚合物基质，通过原位光聚合制成，可以调节胰岛素缺乏的糖尿病小鼠和小型猪的血糖（对于体重为25公斤的小型猪，葡萄糖调节持续20小时，贴片为5厘米(2)）。在高血糖条件下，聚合物基质中的苯硼酸单元可逆地形成葡萄糖-硼酸复合物，由于其负电荷增加，诱导聚合物基质膨胀，削弱带负电荷的胰岛素与聚合物之间的静电相互作用，促进胰岛素的快速释放。这一概念验证演示可能有助于开发其他用于药物递送的翻译刺激反应微针贴片。
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 beta-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 cm(2)). 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.