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无创载有胰高血糖素的溶解微针用于糖尿病大鼠模型严重低血糖急救治疗的实用性。

Practicality of non-invasive glucagon-loaded dissolving microneedle for life-saving treatment of severe hypoglycemia in a diabetic rat model.

机构信息

School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China.

School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China; National Clinical Drug Monitoring Center, Department of Pharmacy, Hebei Province General Center, Shijiazhuang 050051, China.

出版信息

Int J Pharm. 2023 Sep 25;644:123340. doi: 10.1016/j.ijpharm.2023.123340. Epub 2023 Aug 23.

Abstract

The development of dissolving microneedles (DMNs) has brought light to the transdermal delivery of biomolecules that are released into the skin through the rapid dissolution of the matrix material to enter the systemic circulation and exert therapeutic effects. Herein, we aimed to prepare, characterize, and analyze the effectiveness of a glucagon-loaded DMN system that rapidly increases blood sugar levels in rats with diabetic hypoglycemia. The stability and content of biological drugs following DMNs preparation was assessed using circular dichroism and bicinchoninic acid kit for protein determination kits(BCA kits). The maximum drug loading capacity of DMNs was approximately 140 μg in each patch, and the microneedles could be stored for up to 14 days under dry storage conditions. In vitro skin permeation studies were conducted using a Franz diffusion cell apparatus for glucagon-loaded DMNs. To investigate the efficacy of transdermal drug delivery, drug-laden DMNs were administered to rats with hypoglycemic diabetes. Compared to subcutaneous injections, microneedle drug release demonstrated comparable efficacy in raising blood glucose levels in vivo. Therefore, this study demonstrated that glucagon-loaded DMNs may be a promising approach for efficient transdermal drug delivery as an alternative to subcutaneous injection for the treatment of severe hypoglycemia in patients with diabetes.

摘要

溶解微针(DMN)的发展为生物分子的透皮递送带来了曙光,这些生物分子通过基质材料的快速溶解释放到皮肤中,进入体循环并发挥治疗作用。在此,我们旨在制备、表征和分析一种载有胰高血糖素的 DMN 系统的有效性,该系统可快速提高糖尿病低血糖大鼠的血糖水平。使用圆二色性和双缩脲试剂盒(BCA 试剂盒)评估 DMNs 制备后生物药物的稳定性和含量。每个贴片的最大药物载量约为 140μg,并且在干燥储存条件下,微针可以储存长达 14 天。使用 Franz 扩散池装置进行了载有胰高血糖素的 DMNs 的体外皮肤渗透研究。为了研究透皮药物递送的效果,将载有药物的 DMNs 施用于患有低血糖糖尿病的大鼠。与皮下注射相比,微针药物释放在体内升高血糖水平方面显示出相当的效果。因此,这项研究表明,载有胰高血糖素的 DMNs 可能是一种有前途的高效透皮药物递送方法,可替代皮下注射治疗糖尿病患者的严重低血糖。

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