Purpose: The polysaccharide chitosan is a unique material for the design of ocular drug-delivery vehicles. The aim of this study was to radiolabel chitosan with iodine-124 ((124)I) for measurement of ocular pharmacokinetics in rabbits using small-animal positron emission tomography (PET).
Procedures: Crl:CHBB (HM) rabbits received one drop (35 µL) of either a formulation containing chitosan (0.5%, w/v) spiked with (124)I-labeled chitosan ([(124)I]chitosan) (n = 4) or a control solution of sodium [(124)I]iodide in buffer (n = 2) in the conjunctival sac of the right eye. Radioactivity distribution in the head region was measured at five different time points between 0 and 22 h after topical application. Regions of interest were manually defined in the reconstructed PET images, and activity concentration was quantified as percent applied dose (AD) per cubic centimeter tissue.
Results: Clear differences were observed in the ocular pharmacokinetics of the two formulations. At 3 h after application, ocular activity uptake was 0.5 ± 0.1%AD/cc for sodium [(124)I]iodide, compared to 4.7 ± 5.3%AD/cc for the [(124)I]chitosan formulation.
Conclusions: We were able to show that ocular pharmacokinetics of (124)I-labeled ophthalmic formulations can be measured with small-animal PET and that [(124)I]chitosan had approximately a 2-fold increased ocular retention through the study period compared to sodium [(124)I]iodide.