School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
J Control Release. 2011 Sep 5;154(2):148-55. doi: 10.1016/j.jconrel.2011.05.021. Epub 2011 May 26.
Over the past decade, microneedles have been shown to dramatically increase skin permeability to a broad range of compounds by creating reversible microchannels in the skin. However, in order to achieve sustained transdermal drug delivery, the extent and duration of skin's increased permeability needs to be determined. In this study, we used electrical impedance spectroscopy to perform the first experiments in human subjects to analyze the resealing of skin's barrier properties after insertion of microneedles. Microneedles having a range of geometries were studied in conjunction with the effect of occlusion to test the hypothesis that increasing microneedle length, number, and cross-sectional area together with occlusion leads to an increase in skin resealing time that can exceed one day. Results indicated that in the absence of occlusion, all microneedle treated sites recovered barrier properties within 2 h, while occluded sites resealed more slowly, with resealing windows ranging from 3 to 40 h depending on microneedle geometry. Upon subsequent removal of occlusion, the skin barrier resealed rapidly. Longer microneedles, increased number of needles, and larger cross-sectional area demonstrated slower resealing kinetics indicating that microneedle geometry played a significant role in the barrier resealing process. Overall, this study showed that pre-treatment of skin with microneedles before applying an occlusive transdermal patch can increase skin permeability for more than one day, but nonetheless allow skin to reseal rapidly after patch removal.
在过去的十年中，已经证明微针通过在皮肤中创建可逆的微通道，可以极大地增加皮肤对各种化合物的通透性。然而，为了实现持续的经皮药物输送，需要确定皮肤通透性增加的程度和持续时间。在这项研究中，我们使用电阻抗光谱法首次在人体受试者中进行实验，以分析微针插入后皮肤屏障特性的重新密封情况。研究了具有不同几何形状的微针，并结合了封闭的效果，以检验以下假设：增加微针的长度、数量和横截面积以及封闭会导致皮肤重新密封时间延长，甚至超过一天。结果表明，在没有封闭的情况下，所有微针处理部位在 2 小时内恢复了屏障特性，而封闭部位的重新密封速度较慢，根据微针的几何形状，重新密封窗口范围为 3 至 40 小时。随后去除封闭后，皮肤屏障迅速重新密封。较长的微针、更多的针数和更大的横截面积表明，重新密封的动力学较慢，这表明微针的几何形状在屏障重新密封过程中起着重要作用。总体而言，这项研究表明，在应用封闭性经皮贴剂之前，用微针预处理皮肤可以使皮肤通透性增加一天以上，但在去除贴剂后仍能迅速重新密封。
