Improvement of Transdermal Delivery of Exendin-4 Using Novel Tip-Loaded Microneedle Arrays Fabricated from Hyaluronic Acid

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• 作者：Shu Liu ; Dan Wu ; Ying-shu Quan ; Fumio Kamiyama ; Kosuke Kusamori ; Hidemasa Katsumi ; Toshiyasu Sakane ; Akira Yamamoto
• 刊名：Molecular Pharmaceutics
• 出版年：2016
• 出版时间：January 4, 2016
• 年：2016
• 卷：13
• 期：1
• 页码：272-279
• 全文大小：455K
• ISSN：1543-8392

文摘

The purpose of this study was to evaluate the characteristics of exendin-4 tip-loaded microneedle arrays and to compare their acute efficacy with subcutaneous injections in type 2 diabetic GK/Slc rats. Fluorescein isothiocyanate labeled dextran with an average molecular weight of 4,000 (FD4) was selected as a model drug, and FD4 tip-loaded microneedle arrays were prepared in this study. In addition, intraperitoneal glucose tolerance tests after application of exendin-4 tip-loaded microneedle arrays were also compared with those after subcutaneous injection in type 2 diabetic GK/Slc rats. The release of FD4 from the tip-loaded microneedle arrays was very rapid, particularly in the initial 30 s, and most of the FD4 was released within 5 min. In addition, glucose tolerance was improved and the insulin secretion was enhanced after application of exendin-4 tip-loaded microneedle arrays, and these effects were comparable to those after subcutaneous injection of exendin-4. Similar plasma concentration profiles were seen after application of exendin-4 tip-loaded microneedle arrays, as was the case with subcutaneous injection in type 2 diabetic GK/Slc rats. These findings indicate that exendin-4 tip-loaded microneedle arrays can be used as an alternative to achieve sufficient delivery of exendin-4 for treatment of type 2 diabetes. To our knowledge, this is the first report of transdermal exendin-4 delivery using tip-loaded microneedle arrays.