Abstract：
The timely administration of glucagon is a standard clinical practice for the treatment of severe hypoglycemia. However, the process involves cumbersome steps, including the reconstitution of labile glucagon and filling of the syringe, which cause considerable delays in emergency situations. Moreover, multiple dosages are often required to prevent the recurrence of the hypoglycemic episode because of the short half-life of glucagon in plasma. Herein, we develop a glucagon-loaded long-dissolving microneedle (GLMN) patch that exhibits the properties of fast onset and sustained activity for the effective treatment of severe hypoglycemia. Three types of MN patches were fabricated with different dimensions (long, medium, and short). The longer MN patch packaged a higher dosage of glucagon and exhibited supreme mechanical strength compared to the shorter one. Additionally, the longer MN patch could insert more deeply into the skin, resulting in higher permeability of glucagon across the skin tissue and more rapid systemic absorption as compared with the shorter MN patch. The GLMN patch was observed to reverse the effects of hypoglycemia within 15 min of application in animal models (specifically, rat and rhesus monkey models) and maintained long-term glycemic control, owing to highly efficient drug permeation and the drug reservoir effect of the MN base. The current study presents a promising strategy for the rapid reversal of severe hypoglycemia that exhibits the desirable properties of easy use, high efficiency, and sustained action.
摘要：
及时给予胰高血糖素是治疗严重低血糖的标准临床实践。然而,这个过程涉及繁琐的步骤，包括不稳定的胰高血糖素的重建和注射器的填充，这会在紧急情况下造成相当大的延误。此外，由于胰高血糖素在血浆中的半衰期较短,因此通常需要多剂量来预防低血糖事件的复发.在这里，我们开发了一种加载胰高血糖素的长溶解微针（GLMN）贴片，该贴片具有快速起效和持续活性的特性，可有效治疗严重的低血糖。制作了三种不同尺寸的MN贴片(长，中等,和短)。较长的MN贴剂包装较高剂量的胰高血糖素,并且与较短的贴剂相比表现出最高的机械强度。此外,时间越长的MN贴片可以更深入地插入皮肤，与较短的MN贴片相比,导致胰高血糖素穿过皮肤组织的更高的渗透性和更快的全身吸收。观察到GLMN贴片在动物模型中应用15分钟内逆转了低血糖的影响（特别是，大鼠和恒河猴模型）并保持长期血糖控制，由于MN碱的高效药物渗透和药物储库效应。目前的研究提出了一种快速逆转严重低血糖的有希望的策略，表现出易于使用的理想特性，效率高,和持续的行动。
