In vitro and Computational Modelling of Drug Delivery across the Outer Blood-Retinal Barrier

The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer bloodretinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow. This study reports the development of complementary in vitro and in silico models to study drug transport from silicone oil across the outer blood-retinal barrier. Monolayer cultures of a human retinal pigmented epithelium cell line, ARPE-19, were added to chambers and exposed to a controlled flow to simulate drug clearance across the OBRB. Movement of dextran molecules and release of ibuprofen from silicone oil in this model were measured. Corresponding simulations were developed using COMSOL Multiphysics computational fluid dynamics (CFD) software and validated using independent in vitro data sets. Computational simulations were able to predict dextran movement and ibuprofen release, with all of the features of the experimental release profiles being observed in the simulated data. Simulated values for peak concentrations of permeated dextran and ibuprofen released from silicone oil were within 18% of the in vitro results. This model could be used as a predictive tool of drug transport across this important tissue