Permeability and diffusion in vitreous humor: implications for drug delivery

Previous experimental work suggests that convection may be important in determining the biodistribution of drugs implanted or injected in the vitreous humor. To develop accurate biodistribution models, the relative importance of diffusion and convection in intravitreal transport must be assessed. This requires knowledge of both the diffusivity of candidate drugs and the hydraulic conductivity of the vitreous humor.

Hydraulic conductivity of cadaveric bovine vitreous humor was measured by confined compression tests at constant loads of 0.15 and 0.2 N and analyzed numerically using a two-phase model. Diffusion coefficient of acid orange 8, a model compound, in the same medium was measured in a custom-built diffusion cell.

Acid orange 8 diffusivity within vitreous humor is about half that in free solution. When viscous effects are properly accounted for, the hydraulic conductivity of bovine vitreous humor is 8.4+/-4.5 x 10(-7) cm2/Pa x s.

We predict that convection does not contribute significantly to transport in the mouse eye, particularly for low-molecular-weight compounds. For delivery to larger animals, such as humans we conclude that convection accounts for roughly 30% of the total intravitreal drug transport. This effect should be magnified for higher-molecular-weight compounds, which diffuse more slowly, and in glaucoma, which involves higher intraocular pressure and thus potentially faster convective flow. Thus, caution should be exercised in the extrapolation of small-animal-model biodistribution data to human scale.