Kinetics of skin resealing after insertion of microneedles in human subjects.

Kinetics of skin resealing after insertion of microneedles in human subjects.
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DOI:
10.1016/j.jconrel.2011.05.021
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发表时间:
2011-09-05
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Prausnitz MR
Prausnitz MR
中科院分区:
其他
文献类型:
--
作者:
Gupta J;Gill HS;Andrews SN;Prausnitz MR

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在过去的十年中,微针已被证明通过在皮肤中创建可逆的微通道来显著增加皮肤对各种化合物的渗透性。然而,为了实现持续的经皮药物递送,需要确定皮肤渗透性增加的程度和持续时间。在这项研究中,我们使用电阻抗谱法在人类受试者中进行了第一次实验,以分析插入微针后皮肤屏障特性的重新密封。研究了具有一系列几何形状的微针以及闭塞的影响,以检验以下假设:增加微针长度、数量和横截面积以及闭塞导致皮肤重新密封时间增加,可能超过一天。结果表明,在没有闭塞的情况下,所有微针处理的部位在2小时内恢复屏障性能,而闭塞部位重新密封更慢,根据微针几何形状,重新密封窗口范围为3-40小时。在随后去除闭塞后,皮肤屏障迅速重新密封。较长的微针、增加的针数量和较大的横截面积表现出较慢的再密封动力学,表明微针几何形状在屏障再密封过程中起着重要作用。总的来说,这项研究表明,在应用封闭性透皮贴剂之前用微针预处理皮肤可以增加皮肤渗透性超过一天,但仍然允许皮肤在贴剂去除后快速重新密封。
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 3-40 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.
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