The effect of hydration and matrix composition on solute diffusion in rabbit sclera

There is increasing interest in the possibility for drug delivery into the vitreous humor across the conjunctiva and sclera as an alternative route to the conjunctiva-cornea pathway. As a preliminary to human studies we have investigated the influence of scleral composition and hydration on solute transport in the rabbit sclera. Intermuscular sclera was excised from adult New Zealand rabbits. Tissue samples were either examined directly (controls), digested using chondroitinase ABC or crosslinked using glutaraldehyde. The effect of these treatments on the ultrastructural appearance of the sclera was assessed. Diffusion and partition coefficients for solutes of different molecular weights [sodium chloride (23 MW), C-14 sucrose (342 MW) and dextran-fluoresceins (3, 10, 40 and 70 Kda)] were measured in relation to tissue treatment. The results were used to determine the effect of tissue structure and composition on solute movement. We have found that: (1) diffusion and partition coefficients are sensitive to solute MW, decreasing as MW increases; (2) diffusion and partition coefficients are sensitive to tissue hydration, increasing as hydration increases; (3) crosslinking of the sclera by glutaraldehyde reduced the partition coefficients significantly for solutes with MW over 3 kDa; and (4) removal of glycosaminoglycans has only a small effect on either diffusion or the partition coefficient. (C) 2000 Academic Press.