Examination of penetration routes and distribution of ionic permeants during and after transscleral iontophoresis with magnetic resonance imaging
Examination of penetration routes and distribution of ionic permeants during and after transscleral iontophoresis with magnetic resonance imaging
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DOI：
10.1016/j.ijpharm.2006.11.001
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发表时间：
2007-04-20
影响因子：
5.8
通讯作者：
Li, S. Kevin
中科院分区：
文献类型：
--
作者：
Molokhia, Sarah A.;Jeong, Eun-Kee;Li, S. Kevin
在此之前，使用核磁共振成像(MRI)研究了经巩膜和经角膜的离子导入，并与被动导入和玻璃体内注射进行了比较。本研究的目的是利用MRI进一步研究影响经巩膜离子导入的因素。本研究在体外和体内实验中，分别用摘除的巩膜在并列扩散池中进行了阴阳极恒流离子导入。总电流2 mA，作用时间20~60min，电流密度分别为10和20 mA/cm(2)。用核磁共振技术测定模型渗透剂锰离子(Mn2+)和乙二胺四乙酸锰络合物(MnEDTA(2-))在眼内离子导入过程中的转运和分布，并与以往结膜下注射和被动给药的研究结果进行比较。在体外和体内实验中，与被动转运相比，阳极型和阴极型离子导入均显著增强了眼部给药。经巩膜离子导入与体内离子导入的部位和持续时间有关。观察到，当平坦部是应用部位时，渗透剂主要被输送到眼睛的前段。延长这个部位的离子导入时间，可以使渗透剂进入玻璃体的深度和程度比应用部位在眼后靠近穹隆的情况下更深、更大。结果表明，电极位置是影响经巩膜离子导入的重要因素，睫状体(平坦部)是离子导入阻力最小的通道。这些新的发现继续支持MRI作为一种非侵入性技术在眼部给药研究和测试中的应用。(C)2006爱思唯尔B.V.保留所有权利。
Previously, transscleral and transcorneal iontophoretic delivery was studied and compared to passive delivery and intravitreal injection using nuclear magnetic resonance imaging (MRI). The objective of the present study was to employ MRI to further investigate the factors affecting transscleral iontophoretic delivery. In the present study, anodal and cathodal constant current transscleral iontophoresis were conducted with excised sclera in side-by-side diffusion cells in vitro and with rabbits in vivo. The total current and duration of application were 2 and 4 mA (current density 10 and 20 mA/cm(2)) and 20-60 min, respectively. The delivery and distribution of the model permeants manganese ion (Mn2+) and manganese ethylenediaminetetraacetic acid complex (MnEDTA(2-)) into the eye during iontophoresis were determined with MRI and compared with the results obtained in previous studies of subconjunctival injection and passive delivery. Both anodal and cathodal iontophoresis provided significant enhancement in ocular delivery compared to passive transport in the in vitro and in vivo experiments. Transscleral iontophoretic delivery was related to the position and duration of the iontophoresis application in vivo. Permeants were observed to be delivered primarily into the anterior segment of the eye when the pars plana was the application site. Extending the duration of iontophoresis at this site allowed the permeants to be delivered into the vitreous more deeply and to a greater extent than when the application site was at the back of the eye near the fornix. The present results show that electrode placement was an important factor in transscleral iontophoresis, and the ciliary body (pars plana) was determined to be the pathway of least resistance for iontophoretic transport. These new findings continue to support the utility of MRI as a noninvasive technique in ocular drug delivery research and testing. (c) 2006 Elsevier B.V. All rights reserved.