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用于 1 型糖尿病治疗的溶解型和葡萄糖响应型胰岛素释放微针贴片。

A dissolving and glucose-responsive insulin-releasing microneedle patch for type 1 diabetes therapy.

机构信息

School of Power and Mechanical Engineering & The Institute of Technological Science, Wuhan University, 430072, Wuhan, China.

出版信息

J Mater Chem B. 2021 Jan 28;9(3):648-657. doi: 10.1039/d0tb02133d.

Abstract

Diabetes and its complications have become crucial public health challenges worldwide. In this study, we aim to develop a dissolving and glucose-responsive insulin-releasing microneedle (MN) patch system, for minimally invasive and glucose-responsive insulin delivery for type 1 diabetes therapy. The MNs were composed of dissolving and biodegradable gelatin and starch materials, which encapsulated glucose-responsive insulin-releasing gold nanocluster (AuNC) nanocarriers. The fabricated MNs had a complete and uniform structure, consisting of an array of 11 × 11 conical needles, with a needle height of 756 μm, a bottom diameter of 356 μm, a tip diameter of 10 μm, and a tip-to-tip distance of 591 μm. The encapsulated AuNC nanocarriers as additives in the MNs enhanced the mechanical strength of the MNs, and facilitated the penetration of the MNs into the skins of mice. Moreover, the AuNC nanocarrier drugs in the MNs enabled MN patches with a glucose-responsive insulin releasing behavior. With one transdermal application of MN patches on the dorsal skin of mice, the MN patches effectively regulated the BG levels of mice in normoglycemic ranges for 1 to 2 days, and effectively alleviated the diabetic symptoms in type 1 diabetic mice. This dissolving and glucose-responsive insulin-releasing MN patch system realized a closed-loop administration of insulin with minimal invasion, providing great potential applications for type 1 diabetes therapy.

摘要

糖尿病及其并发症已成为全球重要的公共健康挑战。本研究旨在开发一种可溶解且对葡萄糖响应的胰岛素释放微针(MN)贴片系统,用于 1 型糖尿病治疗的微创和葡萄糖响应胰岛素输送。MN 由可溶解和可生物降解的明胶和淀粉材料组成,其封装了葡萄糖响应的胰岛素释放金纳米团簇(AuNC)纳米载体。所制备的 MN 具有完整且均匀的结构,由 11×11 个锥形针的阵列组成,针高为 756μm,底直径为 356μm,针尖直径为 10μm,针尖到针尖的距离为 591μm。作为 MN 中添加剂的封装的 AuNC 纳米载体增强了 MN 的机械强度,并促进了 MN 进入小鼠皮肤的穿透。此外,MN 中的 AuNC 纳米载体药物使 MN 贴片具有葡萄糖响应的胰岛素释放行为。通过在小鼠背部皮肤单次透皮应用 MN 贴片,MN 贴片可有效将小鼠的 BG 水平调节至正常血糖范围 1 至 2 天,并有效缓解 1 型糖尿病小鼠的糖尿病症状。这种可溶解且对葡萄糖响应的胰岛素释放 MN 贴片系统实现了最小侵入性的胰岛素闭环管理,为 1 型糖尿病治疗提供了巨大的应用潜力。

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