In Vitro and Ex Vivo Models for Assessing Drug Permeation across the Cornea

Drugpermeation across the cornea remains a major challenge dueto its unique and complex anatomy and physiology. Static barrierssuch as the different layers of the cornea, as well as dynamic aspectssuch as the constant renewal of the tear film and the presence ofthe mucin layer together with efflux pumps, all present unique challengesfor effective ophthalmic drug delivery. To overcome some of the currentophthalmic drug limitations, the identification and testing of noveldrug formulations such as liposomes, nanoemulsions, and nanoparticlesbegan to be considered and widely explored. In the early stages ofcorneal drug development reliable in vitro and ex vivo alternatives, are required, to be in line with theprinciples of the 3Rs (Replacement, Reduction, and Refinement), withsuch methods being in addition faster and more ethical alternativesto in vivo studies. The ocular field remains limitedto a handful of predictive models for ophthalmic drug permeation. In vitro cell culture models are increasingly used whenit comes to transcorneal permeation studies. Ex vivo models using excised animal tissue such as porcine eyes are themodel of choice to study corneal permeation and promising advancementshave been reported over the years. Interspecies characteristics mustbe considered in detail when using such models. This review updatesthe current knowledge about in vitro and ex vivo corneal permeability models and evaluates theiradvantages and limitations.