Improvement of Transdermal Delivery of Exendin-4 Using Novel Tip-Loaded Microneedle Arrays Fabricated from Hyaluronic Acid
Improvement of Transdermal Delivery of Exendin-4 Using Novel Tip-Loaded Microneedle Arrays Fabricated from Hyaluronic Acid
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DOI：
10.1021/acs.molpharmaceut.5b00765
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发表时间：
2016-01-01
影响因子：
4.9
通讯作者：
Yamamoto, Akira
中科院分区：
文献类型：
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作者：
Liu, Shu;Wu, Dan;Yamamoto, Akira
本研究的目的是评估 exendin-4 尖端装载微针阵列的特性，并比较其与皮下注射对 2 型糖尿病 GK/Slc 大鼠的急性疗效。本研究选择平均分子量为4000的异硫氰酸荧光素标记的右旋糖酐（FD4）作为模型药物，制备了FD4尖端装载的微针阵列。此外，还对2型糖尿病GK/Slc大鼠应用Exendin-4尖端装载微针阵列后的腹腔内葡萄糖耐量测试与皮下注射后的腹腔内葡萄糖耐量测试进行了比较。 FD4从尖端装载的微针阵列中的释放非常快，特别是在最初的30秒内，并且大部分FD4在5分钟内释放。此外，应用Exendin-4尖端装载微针阵列后，糖耐量得到改善，胰岛素分泌增强，这些效果与皮下注射Exendin-4后的效果相当。与 2 型糖尿病 GK/Slc 大鼠皮下注射的情况一样，应用 exendin-4 尖端装载的微针阵列后，观察到类似的血浆浓度分布。这些发现表明，Exendin-4 尖端装载的微针阵列可作为替代方案，以实现 Exendin-4 的充分递送，以治疗 2 型糖尿病。据我们所知，这是使用尖端加载的微针阵列进行透皮 Exendin-4 递送的第一份报告。
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.