Modeling the Flow and Fate of Ocular Drugs Using Micro-CT

Abstract

Purpose: : Many ocular drugs have a narrow therapeutic window of effectiveness and are potentially toxic at higher concentrations. Predicting the delivery of these drugs from an intravitreal injection to the retina is therefore of great interest. The purpose of this work is to create a method of assessing the concentration and transport mechanism of ocular drug surrogates following mid-vitreal injections in ex vivo and in vivo animal models.

Methods: : Three dimensional micro-computed tomography images acquired at varying time points following an intravitreal injection of gold nanoparticle contrast agent were used. A combination of volumetric regions of interest and linear signal intensity profiles were used to measure the contrast agent movement in the vitreous. Closed form mathematical solutions for diffusive transport and computer-based numerical modeling were used to predict the transport and fate of the drug surrogates.

Results: : Using a passive diffusion equation provides an acceptable model for the intravitreal injection, particularly in the horizontal direction. Concentration profiles in the vertical direction lack symmetry due to a gravitational component. Non-linear regression is used as a means of comparing experimental data with that of the computed predicted data and provides a measure for optimization results.

Conclusions: : Live imaging of experimental data was used to develop and validate a model of ocular drug flow and fate in the eye. This approach permits the development of more accurate predictive tools to provide the medical community with the ability to design and test new drugs and drug delivery systems for clinical application.

Keywords: imaging/image analysis: non-clinical • vitreous