Hao Jinsong, Li S Kevin
Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267, USA.
J Pharm Sci. 2008 Feb;97(2):893-905. doi: 10.1002/jps.21025.
Transungual iontophoretic transport of model neutral permeants mannitol (MA), urea (UR), and positively charged permeant tetraethylammonium ion (TEA) across fully hydrated human nail plates at pH 7.4 were investigated in vitro. Four protocols were involved in the transport experiments with each protocol divided into stages including passive and iontophoresis transport of 0.1 and 0.3 mA. Water and permeant uptake experiments of nail clippings were also conducted to characterize the hydration and binding effects of the permeants to the nails. Iontophoresis enhanced the transport of MA and UR from anode to cathode, but this effect (electroosmosis) was marginal. The transport of TEA was significantly enhanced by anodal iontophoresis and the experimental enhancement factors were consistent with the Nernst-Planck theory predictions. Hindered transport was also observed and believed to be critical in transungual delivery. The barrier of the nail plates was stable over the time course of the study, and no significant electric field-induced alteration of the barrier was observed. The present results with hydrated nail plates are consistent with electrophoresis-dominant (the direct field effect) transungual iontophoretic transport of small ionic permeants with small contribution from electroosmosis.
体外研究了模型中性渗透剂甘露醇(MA)、尿素(UR)以及带正电荷的渗透剂四乙铵离子(TEA)在pH 7.4条件下通过完全水合的人指甲板的经甲离子电渗转运。转运实验涉及四种方案,每种方案分为不同阶段,包括0.1 mA和0.3 mA的被动和离子电渗转运。还进行了指甲剪屑的水和渗透剂摄取实验,以表征渗透剂对指甲的水合和结合作用。离子电渗增强了MA和UR从阳极到阴极的转运,但这种效应(电渗)很微弱。阳极离子电渗显著增强了TEA的转运,实验增强因子与能斯特-普朗克理论预测一致。还观察到了转运受阻现象,并且认为这在经甲递送中至关重要。在研究的时间过程中,指甲板的屏障是稳定的,未观察到明显的电场诱导的屏障改变。水合指甲板的当前结果与小离子渗透剂以电泳为主(直接场效应)的经甲离子电渗转运一致,电渗的贡献较小。