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

## TL;DR

This study examines how drug delivery to the retina and vitreous humor varies across species and drug properties, finding that delivery is influenced by eye size and drug characteristics.

## Contribution

The paper introduces a unified predictive model for suprachoroidal drug delivery that incorporates eye diameter and drug physicochemical properties across multiple species.

## Key findings

- Drug concentrations in the retina were higher than in the vitreous humor across all species.
- A predictive equation incorporating eye diameter and drug properties explained 74% of retinal and 93% of vitreous concentration variance.
- Drug delivery decreased with increasing eye diameter (rabbit > porcine > bovine).

## Abstract

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 (LogD7.4: −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 (LogD7.4), 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*LogD7.4 + 0.106*LogS + 0.004*TPSA + 0.395*1/d2. Vitreous humor delivery scaled for all species: Log FD/g = -1.898–0.047*LogD7.4 − 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.

The online version contains supplementary material available at 10.1038/s41598-025-34631-x.