Transdermal delivery of desmopressin using a coated microneedle array patch system
Transdermal delivery of desmopressin using a coated microneedle array patch system
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DOI：
10.1016/j.jconrel.2004.04.003
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发表时间：
2004-07-07
影响因子：
10.8
通讯作者：
Daddona, P
中科院分区：
文献类型：
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作者：
Cormier, M;Johnson, B;Daddona, P
去氨加压素是一种合成肽类激素，主要用于治疗小儿遗尿症。它可用于注射，鼻内和口服制剂。虽然注射给药不太适合幼儿的常规使用，但鼻内和口服给药导致生物利用度低且可变。因此，本研究探索了使用Macroflux（R）技术经皮施用去氨加压素的可行性，该技术使用微针阵列来克服皮肤屏障。在2 cm（2）阵列的微针尖端覆盖不同数量的去氨加压素固体涂层，并应用于无毛豚鼠皮肤5或15 min。5 min后递送药理学相关量的去氨加压素。生物利用度高达85%，并显示可接受的变异性（30%）。免疫反应性血清去氨加压素达到峰值水平后，Tmax为60分钟。消除动力学血清去氨加压素是相似的经皮和静脉内（IV）输送后，这表明没有皮肤贮库。在施用后，在皮肤表面上发现仅10%的加载到微针阵列上的去氨加压素剂量。此外，贴剂耐受性良好。这些结果表明，通过Macroflux（R）经皮递送去氨加压素是目前可用的给药途径的安全且有效的替代方案。(C)2004 Elsevier B.V.保留所有权利。
Desmopressin is a synthetic peptide hormone chiefly used for treatment of enuresis in young children. It is available in injectable, intranasal, and oral formulations. While administration by injection is poorly suited for routine use in young children, intranasal and oral administration result in low and variable bioavailability. This study therefore explored the feasibility of administering desmopressin transdermally using Macroflux(R) technology, which uses a microneedle array to overcome the skin barrier. The tips of microneedles in 2-cm(2) arrays were covered with a solid coating of various arnounts of desmopressin and applied to the skin of hairless guinea pigs for 5 or 15 min. Pharmacologically relevant amounts of desmopressin were delivered after 5 min. Bioavailability was as high as 85% and showed acceptable variability (30%). Immunoreactive serum desmopressin reached peak levels after a T-max of 60 min. Elimination kinetics for serum desmopressin was similar after transdermal and intravenous (IV) delivery, suggesting the absence of a skin depot. Only 10% of the desmopressin dose loaded onto the microneedle array was found on the skin surface after application. Additionally, the patches were well tolerated. These results suggest that transdermal delivery of desmopressin by Macroflux(R) is a safe and efficient alternative to currently available routes of administration. (C) 2004 Elsevier B.V. All rights reserved.