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Glucose-Responsive Microneedle Patch with High Insulin Loading Capacity for Prolonged Glycemic Control in Mice and Minipigs
ACS Nano ( IF 15.8 ) Pub Date : 2024-09-11 , DOI: 10.1021/acsnano.4c05562 Shiqi Wang 1 , Changwei Yang 1 , Wentao Zhang 1 , Sheng Zhao 1 , Jiahuan You 1 , Ruisi Cai 1 , Hao Wang 1 , Yuhang Bao 1 , Ying Zhang 1 , Juan Zhang 1 , Kangfan Ji 1 , Yuqi Zhang 1, 2 , Xiao Ye 3, 4 , Zhen Gu 1, 5, 6, 7, 8 , Jicheng Yu 1, 5, 6, 7
ACS Nano ( IF 15.8 ) Pub Date : 2024-09-11 , DOI: 10.1021/acsnano.4c05562 Shiqi Wang 1 , Changwei Yang 1 , Wentao Zhang 1 , Sheng Zhao 1 , Jiahuan You 1 , Ruisi Cai 1 , Hao Wang 1 , Yuhang Bao 1 , Ying Zhang 1 , Juan Zhang 1 , Kangfan Ji 1 , Yuqi Zhang 1, 2 , Xiao Ye 3, 4 , Zhen Gu 1, 5, 6, 7, 8 , Jicheng Yu 1, 5, 6, 7
Affiliation
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Transdermal microneedle-mediated glucose-responsive insulin delivery systems can modulate insulin release based on fluctuations in blood glucose levels, thus maintaining normoglycemia effectively in a continuous, convenient, and minimally invasive manner. However, conventional microneedles are limited by the low drug loading capacity, making it challenging to be applied on human skin at a reasonable size for a lasting glucose-controlling effect, thus hindering their clinical translation. Here, we design a microneedle patch with a solid insulin powder core to achieve a high loading capacity of insulin (>70 wt %) as well as a glucose-sensitive polymeric shell to realize glucose-responsive insulin release. Once exposed to hyperglycemia, the formation of negatively charged glucose–boronate complexes increases the charge density of the shell matrix, leading to swelling of the shell and accelerating insulin release from the core. We have demonstrated that this glucose-responsive microneedle patch could achieve long-term regulation of blood glucose levels in both type 1 diabetic mice and minipigs (up to 48 h with patches of ∼3.5 cm2 for minipigs >25 kg).
中文翻译：
具有高胰岛素负荷能力的葡萄糖响应微针贴片，可延长小鼠和小型猪的血糖控制
透皮微针介导的葡萄糖反应性胰岛素输送系统可以根据血糖水平的波动调节胰岛素的释放，从而以持续、便捷、微创的方式有效维持正常血糖。然而，传统微针的载药量较低，难以以合理的尺寸应用于人体皮肤以达到持久的血糖控制效果，从而阻碍了其临床转化。在这里，我们设计了一种微针贴片，其具有固体胰岛素粉末核心，以实现胰岛素的高负载能力（>70 wt%），以及葡萄糖敏感的聚合物外壳，以实现葡萄糖响应性胰岛素释放。一旦暴露于高血糖，带负电荷的葡萄糖-硼酸盐复合物的形成会增加壳基质的电荷密度，导致壳膨胀并加速胰岛素从核心的释放。我们已经证明，这种葡萄糖响应微针贴片可以实现对 1 型糖尿病小鼠和小型猪血糖水平的长期调节（对于小型猪 >25 kg，贴片尺寸约为 3.5 cm 2 ，最长可达 48 小时）。
更新日期：2024-09-11
中文翻译：
具有高胰岛素负荷能力的葡萄糖响应微针贴片，可延长小鼠和小型猪的血糖控制
透皮微针介导的葡萄糖反应性胰岛素输送系统可以根据血糖水平的波动调节胰岛素的释放，从而以持续、便捷、微创的方式有效维持正常血糖。然而，传统微针的载药量较低，难以以合理的尺寸应用于人体皮肤以达到持久的血糖控制效果，从而阻碍了其临床转化。在这里，我们设计了一种微针贴片，其具有固体胰岛素粉末核心，以实现胰岛素的高负载能力（>70 wt%），以及葡萄糖敏感的聚合物外壳，以实现葡萄糖响应性胰岛素释放。一旦暴露于高血糖，带负电荷的葡萄糖-硼酸盐复合物的形成会增加壳基质的电荷密度，导致壳膨胀并加速胰岛素从核心的释放。我们已经证明，这种葡萄糖响应微针贴片可以实现对 1 型糖尿病小鼠和小型猪血糖水平的长期调节（对于小型猪 >25 kg，贴片尺寸约为 3.5 cm 2 ，最长可达 48 小时）。
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