Numerical simulations of ethacrynic acid transport from precorneal region to trabecular meshwork

Topical application of drugs for treatment of intraocular diseases is often limited by inadequate transport and induced toxicity in corneal tissues. To improve the drug delivery, a mathematical model was developed to numerically simulate the transport process of ethacrynic acid (ECA), a potential drug for glaucoma treatment, in the anterior segment of a typical human eye. The model considered diffusion of ECA in all tissues and the aqueous humor (AH) as well as convection of ECA in the AH. The simulation results showed that ECA concentration in the eye depended on the rate of AH production, the half-life of ECA in the precorneal tear film, and the transport parameters in the model. In addition, the main pathway for ECA clearance from the eye was the trabecular meshwork (TM) and the rate of clearance was approximately proportional to the AH production rate. The model predicted that the most effective approach to improving topical drug delivery was to prolong its half-life in the precorneal tear film. These simulation results and model prediction, which could be verified experimentally, might be useful for improving delivery of ECA and other therapeutic agents to the TM as well as other tissues in the anterior segment of the eye.