Li S Kevin, Jeong Eun-Kee, Hastings Matthew S
Department of Pharmaceutics, Utah Center for Advanced Imaging Research (Radiology), University of Utah, Salt Lake City, Utah 84112, USA.
Invest Ophthalmol Vis Sci. 2004 Apr;45(4):1224-31. doi: 10.1167/iovs.03-0821.
The objectives were to determine by nuclear magnetic resonance imaging (MRI) the target sites of ion delivery in the eye during iontophoresis, compare transscleral and transcorneal ocular iontophoresis, and monitor the distribution of a probe ion in the anterior chamber and vitreous after iontophoretic delivery.
Thirty-minute 2-mA anodal constant current transscleral and transcorneal iontophoresis (current density, 10 mA/cm(2)) was performed on three New Zealand White rabbits in vivo. Intravitreal injection and passive delivery were the controls. Transscleral and transcorneal iontophoresis experiments were conducted with the electrode device placed in the superior cul-de-sac away from the limbus and on the cornea adjacent to the limbus, respectively. During iontophoresis, the current delivered into the eye was monitored using a probe ion (Mn(2+)) with MRI. The distributions of the ion in the aqueous and vitreous humor after iontophoresis, passive delivery, and intravitreal injection were also determined by MRI.
With the short application time, passive diffusion did not deliver a significant amount of the ion into the eye. Whereas transscleral iontophoresis delivered the ion into the vitreous, transcorneal iontophoresis delivered the ion into the anterior chamber. The current pathways during iontophoresis were mainly from the electrode into the eye, perpendicular to the electrode-eye interface beneath the electrode. Electric current along the surface of the globe was relatively minimal. With the present transscleral iontophoresis protocol, the ion penetrated the sclera and traveled as far as 1.5 mm from the electrode-conjunctiva interface into the vitreous. For transcorneal iontophoresis, the ion penetrated the cornea and filled the entire anterior chamber.
MRI can be a useful technique in the study of the penetration of probe compounds in the eye during and after iontophoresis, such as in iontophoresis protocol and device testing. Ocular pharmacokinetic studies using MRI are noninvasive and provide real-time data without perturbation and compound redistribution that can occur during dissection and assay in traditional pharmacokinetic studies. With MRI, it was shown that transscleral iontophoresis, transcorneal iontophoresis, and intravitreal injection deliver ions to different parts of the eye.
本研究旨在通过核磁共振成像（MRI）确定离子导入过程中眼部离子递送的靶点，比较经巩膜和经角膜眼部离子导入，以及监测离子导入递送后前房和玻璃体中探针离子的分布。
对三只新西兰白兔进行30分钟、2毫安的阳极恒流经巩膜和经角膜离子导入（电流密度为10毫安/平方厘米）。玻璃体内注射和被动递送作为对照。经巩膜和经角膜离子导入实验分别将电极装置置于远离角膜缘的上方结膜囊和靠近角膜缘的角膜上。在离子导入过程中，使用带有MRI的探针离子（Mn²⁺）监测进入眼内的电流。离子导入、被动递送和玻璃体内注射后，房水和玻璃体液中离子的分布也通过MRI确定。
在短时间应用时，被动扩散未能将大量离子递送至眼内。经巩膜离子导入将离子递送至玻璃体，而经角膜离子导入将离子递送至前房。离子导入过程中的电流路径主要是从电极进入眼内，垂直于电极下方的电极-眼界面。沿眼球表面的电流相对较小。按照目前的经巩膜离子导入方案，离子穿透巩膜并从电极-结膜界面进入玻璃体达1.5毫米。对于经角膜离子导入，离子穿透角膜并充满整个前房。
MRI可作为一种有用的技术，用于研究离子导入过程中及之后探针化合物在眼内的渗透，如在离子导入方案和装置测试中。使用MRI的眼部药代动力学研究是非侵入性的，可提供实时数据，且不会出现传统药代动力学研究中解剖和分析过程中可能发生的干扰和化合物重新分布。通过MRI表明，经巩膜离子导入、经角膜离子导入和玻璃体内注射将离子递送至眼的不同部位。
