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1From the Department of Pharmaceutics and Pharmaceutical Chemistry and the 2Utah Center for Advanced Imaging Research (Radiology), University of Utah, Salt Lake City, Utah; and 3Aciont Inc., Salt Lake City, Utah.
PURPOSE. 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.
METHODS. Thirty-minute 2-mA anodal constant current transscleral and transcorneal iontophoresis (current density, 10 mA/cm2) 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 (Mn2+) 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.
RESULTS. 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.
CONCLUSIONS. 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.
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