Permeability and Diffusion in Vitreous Humor: Implications for Drug Delivery

AbstractPurpose. Previous experimental work suggests that convection maybe important in determining the biodistribution of drugs implanted orinjected in the vitreous humor. To develop accurate biodistributionmodels, the relative importance of diffusion and convection inintravitreal transport must be assessed. This requires knowledge of both thediffusivity of candidate drugs and the hydraulic conductivity of thevitreous humor. Methods. Hydraulic conductivity of cadaveric bovine vitreous humorwas measured by confined compression tests at constant loads of 0.15and 0.2 N and analyzed numerically using a two-phase model. Diffusioncoefficient of acid orange 8, a model compound, in the same mediumwas measured in a custom-built diffusion cell. Results. Acid orange 8 diffusivity within vitreous humor is about halfthat in free solution. When viscous effects are properly accounted for,the hydraulic conductivity of bovine vitreous humor is 8.4 ± 4.5 ×10−7 cm2/Pa s. Conclusions. We predict that convection does not contributesignificantly to transport in the mouse eye, particularly forlow-molecular-weight compounds. For delivery to larger animals, such as humanswe conclude that convection accounts for roughly 30% of the totalintravitreal drug transport. This effect should be magnified forhigher-molecular-weight compounds, which diffuse more slowly, and inglaucoma, which involves higher intraocular pressure and thus potentiallyfaster convective flow. Thus, caution should be exercised in theextrapolation of small-animal-model biodistribution data to human scale.