Analysis of drug delivery in the eye using magnetic resonance imaging.

摘要

With the rapid increase in the elderly population, the number of Americans afflicted with vision impairment due to ocular disease is projected to rise substantially by the year 2020. Ocular disorders are becoming a major public health problem, and efforts have increased in recent years to develop methods of efficient drug delivery. Currently, the most effective method for treating serious ocular disorders is to inject drug solutions directly into the vitreous. However, injecting in this manner carries a high risk of severe side effects. As a safer alternative, researchers in recent years have been investigating transscleral drug delivery, in which the drug is administered to the outer coat of the eye. Various methods of transscleral drug delivery have been proposed, but it is still clinically not as effective as intravitreal drug delivery. In order to design improved transscleral drug delivery systems, the ocular barriers to drug transport must be accurately understood.; While various barrier types have been identified in the eye, the significance and contribution of individual barriers have not been investigated and are still widely unknown. A reason for this lack of understanding is due to the inability to acquire concentration measurements in the eye in vivo. In this study, magnetic resonance imaging (MRI) was employed to obtain drug concentration measurements in vivo after transscleral drug delivery.; To address the current needs of the ocular drug delivery community, several goals have been achieved in this work: (1) to evaluate transscleral drug delivery in vivo using MRI, (2) to assess MRI as a technique for evaluating drug delivery in the eye, and (3) to better understand the significance of individual barriers in the eye by quantitatively analyzing experimental (MRI) data and by pharmacokinetic modeling. While encompassing many advantages, it is found that MRI has limitations in spatial and temporal resolution that may restrict its use in measuring parameters with low sensitivity. However, the MRI results in parallel with analysis from the pharmacokinetic model give new insight into the barriers to drug transport in the eye.