In vitro tear replenishment system: assessing drug delivery from contact lens biomaterials through corneal epithelial monolayer and multilayer under replenishment conditions

Abstract

There is a need to develop improved in vitro ocular models for biocompatibility and drug delivery studies to assess the potential of in vivo performance of contact lenses. By using an in vitro corneal epithelial cell model combined with a tear replenishment method, this study aimed to investigate the delivery of the glaucoma drug latanoprost from contact lenses and compare the dynamic release results to no-replenishment (immersion) conditions. Corneal epithelial cells were grown as a monolayer or multilayer on curved cellulose cell culture inserts. Three contact lens materials (balafilcon A; senofilcon A; etafilcon A), soaked for 24 h in latanoprost, were placed on the curved cornea models (CCM) and drug concentration was determined on the basal (diffusion/transport) and apical (supernatant) sides after 1, 4, 8 and 12 h. The in vitro tear replenishment was achieved via intermittent flow of a tear solution over the CCM at a rate of 1 mL/hour. A zero-order kinetic was observed for basal drug concentration over the 12 h period. Similar basal and apical drug concentrations were observed with monolayer and multilayer CCM, except for the etafilcon A material. The apical release of latanoprost was significantly lower under replenishment compared to no-replenishment conditions. These results demonstrate the role that a dynamic release model will have in predicting the amount of drug that can be released from a contact lens into the tear film and the critical role of a cell monolayer in in vitro drug delivery studies. Graphical Abstract