Examination of barriers and barrier alteration in transscleral iontophoresis
Examination of barriers and barrier alteration in transscleral iontophoresis
复制标题
DOI：
10.1002/jps.21003
复制
发表时间：
2008-02-01
影响因子：
3.8
通讯作者：
Li, Kevin
中科院分区：
文献类型：
--
作者：
Molokhia, Sarah;Jeong, Eun-Kee;Li, Kevin
经巩膜电离子导入的通量增强机制还不清楚。本研究的目的是通过磁共振成像（MRI）研究经巩膜电离子导入对眼屏障的影响和屏障的改变。本实验采用恒流离子导入法（电流密度10 mA/cm ~ 2），经巩膜结膜下注射，对家兔进行了活体和死后实验，并对离体巩膜进行了并行扩散池实验。死后和体外实验将有助于阐明血管清除和其他转运屏障在经巩膜离子导入中的重要性。以锰离子（Mn ~（2+））和乙二胺四乙酸锰络合物（MnEDTA（2-））为模型渗透物。结果表明，通过离子电渗法用电场预处理眼睛增强了渗透物在体内结膜下递送至眼前段。这表明电场诱导的屏障改变可能是眼离子导入的重要吸收增强机制。在死后实验中，随着大量渗透物被输送到眼睛和眼睛后部，渗透增强被放大。在体内和死后研究中观察到的不同结果可归因于眼部给药中的眼部清除。(C)2007 Wiley-Liss，Inc.和美国药剂师协会
The flux enhancing mechanisms of transscleral iontophoresis are not well understood. The objective of the present study was to investigate the ocular barrier and barrier alterations in transscleral iontophoretic delivery with magnetic resonance imaging (MRI). Experiments involving constant current transscleral iontophoresis of 2 mA (current density 10 mA/cm(2)) and subconjunctival injection were conducted with rabbits in vivo and postmortem and with excised sclera in side-by-side diffusion cells in vitro. The postmortem and in vitro experiments were expected to be helpful in clarifying the importance of vascular clearance and other transport barriers in transscleral iontophoresis. Manganese ion (Mn2+) and manganese ethylenediaminetetraacetic acid complex (MnEDTA(2-)) were the model permeants. The results show that pretreatment of the eye with an electric field by iontophoresis enhanced subconjunctival delivery of the permeants to the anterior segment of the eye in vivo. This suggests that electric field-induced barrier alterations can be an important absorption enhancing mechanism of ocular iontophoresis. Penetration enhancement was magnified in the postmortem experiments with larger amounts of the permeants delivered into the eye and to the back of the eye. The different results observed in the in vivo and postmortem studies can be attributed to ocular clearance in ocular delivery. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.