Abstract
In early studies, the ‘contour method’ for determining the diffusion coefficient of the vitreous humor was developed. This technique relied on careful injection of an MRI contrast agent (surrogate drug) into the vitreous humor of fresh bovine eyes, and tracking the contours of the contrast agent in time. In addition, an analytical solution was developed for the theoretical contours built on point source model for the injected surrogate drug. The match between theoretical and experimental contours as a least square fit, while floating the diffusion coefficient, led to the value of the diffusion coefficient. This method had its limitation that the initial injection of the surrogate had to be spherical or ellipsoidal because of the analytical result based on the point-source model. With a new finite element model for the analysis in this study, the technique is much less restrictive and handles irregular shapes of the initial bolus. The fresh bovine eyes were used for drug diffusion study in the vitreous and three contrast agents of different molecular masses: gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA, 938 Da), non-ionic gadoteridol (Prohance, 559 Da), and bovine albumin conjugated with gadolinium (Galbumin, 74 kDa) were used as drug surrogates to visualize the diffusion process by MRI. The 3D finite element model was developed to determine the diffusion coefficients of these surrogates with the images from MRI. This method can be used for other types of bioporous media provided the concentration profile can be visualized (by methods such as MRI or fluorescence).
Highlights
During the past decades, many researchers have attempted to develop ocular drug delivery systems
Following the method of diffusion coefficient measurement by using MRI developed earlier, contours of constant concentration were established for different drug surrogates in each eye, and the comparison of these with the corresponding finite element calculation was shown in figure 3 where the (x, y, z) coordinate system in relation to the eye is shown in figure 4
By comparing the diffusion coefficients between Gd-DTPA, Prohance, and Galbumin, we found that Galbumin had the lowest diffusivity, while Gd-DTPA had the highest diffusivity in the vitreous
Summary
Many researchers have attempted to develop ocular drug delivery systems. It is crucial to know the drug distribution within the eye following delivery by intravitreal injection. With the help from the advanced computer software nowadays, ocular drug transport models have been developed to simulate and predict drug distribution in the eye [4,5,6,7]. These models require the values of parameters that are used in the governing equations, and one of the most common uses of parameter is drug diffusivity. The aim of this work is to develop a technique that delivers the values of diffusion coefficient of drugs in the vitreous from MRI images
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