Diffusive Transport in the Vitreous Humor: Experimental and Analytical Studies

Abstract

In relation to intravitreal drug delivery, predictive mathematical models for drug transport are being developed, and to effectively implement these for retinal delivery, the information on biophysical properties of various ocular tissues is fundamentally important. It is therefore necessary to accurately measure the diffusion coefficient of drugs and drug surrogates in the vitreous humor. In this review, we present the studies conducted by various researchers on such measurements over the last several decades. These include imaging techniques (fluorescence and magnetic resonance imaging (MRI)) that make use of introducing a contrast agent or a labeled drug into the vitreous and tracking its diffusive movement at various time points. A predictive model for the same initial conditions when matched with the experimental measurements provides the diffusion coefficient, leading to results for various molecules ranging in size from approximately 0.1 to 160 kDa. For real drugs, the effectiveness of this system depends on the successful labeling of the drugs with suitable contrast agents such as fluorescein and gadolinium or manganese so that fluorescence or MR imagining could be conducted. Besides this technique, some work has been carried out using the diffusion apparatus for measuring permeation of a drug across an excised vitreous body from a donor chamber to the receptor by sampling assays from the chambers at various time intervals. This has the advantage of not requiring labeling but is otherwise more disruptive to the vitreous. Some success with nanoparticles has been achieved using dynamic light scattering (DLS), and presently, radioactive labeling is being explored.