Comparative permeability of human and rabbit corneas to cyclosporin and tritiated water

Diffusion of cyclosporin A (CsA) and water through fresh and frozen (liquid nitrogen, -85 degrees C) human and rabbit corneas was compared to establish the appropriateness of using the latter tissue as a model for its human counterpart for in vitro permeability studies. Permeation of CsA in the presence of three penetration enhancers, 0.01% benzalkonium chloride (BZCl), 20% dimethylsulfoxide (DMSO), 10% and 20% Cremophor-EL was also studied. Permeability was determined using a flow-through diffusion apparatus (20 degrees C, 24 hours). ANOVA, Duncan's multiple range test, and an unpaired t-test were used to determine steady state kinetics and flux differences over time intervals. No statistically significant differences in flux values of CsA and water could be detected between fresh and frozen/thawed human and rabbit corneas. The diffusion of water was significantly lower across frozen/thawed rabbit cornea than across the same human tissue. CsA flux rates across frozen/thawed rabbit cornea in the presence of all three enhancers increased significantly when compared to the same tissues without enhancer, except in the presence of 20% Cremophor-EL after 18 hours. The rabbit cornea appears to be an appropriate in vitro model for studying human transcorneal penetration of drugs. Smaller M(w) substances, however, may have higher diffusion rates across frozen/thawed human corneal tissue.