Interspecies scaling of suprachoroidal drug delivery using ocular geometry and drug physicochemical properties

Excised rabbit, porcine, and bovine eyes were injected in the suprachoroidal space with a cassette of 27 drugs, including 10 beta-blockers, 8 NSAIDs, and 9 corticosteroids, spanning a lipophilicity range (LogD_7.4: -4.18 to 4.70). Drug concentrations in retina and vitreous humor were quantified by LC-MS/MS on both injected and non-injected sides. Most drugs were detected in both tissues, with higher concentrations on the injected side (0.04-3.69 fraction dose or FD/g) compared to the non-injected side (0.00-0.74 FD/g), after excluding eight outliers (drug-prodrug pairs and unstable drugs). Total retinal concentrations (0.07-1.88 FD/g) exceeded vitreous concentrations (0.02-0.40 FD/g). Across species, delivery decreased with eye diameter (rabbit > porcine > bovine). For individual species, multiple linear regression explained 70-83% of variance in retinal concentrations and 45-62% in vitreous concentrations using drug physicochemical properties. A unified equation incorporating 1/d² (d is eye diameter in cm), lipophilicity (LogD_7.4), molar solubility (LogS), and total polar surface area (TPSA) predicted concentrations in all species for a given tissue, explaining 74% of retinal and 93% of vitreous variance. Retinal delivery scaled for all species: Log FD/g = -1.121 + 0.255*LogD_7.4 + 0.106*LogS + 0.004*TPSA + 0.395*1/d². Vitreous humor delivery scaled for all species: Log FD/g = -1.898-0.047*LogD_7.4 - 0.051*LogS + 0.001*TPSA + 0.833*1/d². While this study evaluated static barriers, in vivo delivery is expected to be lower due to dynamic clearance mechanisms.