New pathways for drug and gene delivery to the eye: A mathematical model

Abstract

Drug and gene delivery to the eye, namely to the posterior segment of the eye, is one of the most challenging problems for ophthalmologists and pharmacologists. The reason lies in the fact that the eye is protected by multiple barriers that prevent the permeation of xenobiotics and consequently prevent drugs from permeating ocular tissues. Intravitreal injection (IVI), a procedure that releases the drug directly into the vitreous, has become the gold standard for the treatment of posterior diseases. However, due to its invasiveness, several complications can occur. Medical and pharmaceutical researchers are continuously looking for new compounds, new access routes and new ways of enhancing the release. In recent years, two less invasive routes, subretinal space (SRS) and suprachoroidal space (SCS), have received considerable attention, to target the posterior segment of the eye. The aim of the paper is to present a mathematical model that simulates the coupling of an electric field with SRS or SCS injections, and to show how drug distribution compares with the gold standard, IVI. The model is represented by coupled systems of parabolic and elliptic partial differential equations. The ocular barriers are described with a certain detail. A priori estimates establish qualitative properties of the total mass released. Numerical simulations, in different scenarios, illustrate the comparative behaviour of the three treatments for short and long times. The evolution of mean drug concentration in the different ocular tissues, with and without electrical assistance, is studied.