In most posterior eye diseases, e.g., macular degeneration, the blood-retina barrier breaks. One of the therapeutic modalities for these diseases is the delivery of anti-VEGF agents to the posterior eye to suppress the pathologic vascularization. This is currently done through intravitreal injections administered at a frequency that causes discomfort to both patients and care givers. Sustained delivery of anti-VEGF agents by other routes is currently gaining in popularity.

In this paper, we present a model for sustained delivery of anti-VEGF agents through the sclera. The anti-VEGF agents are macromolecules with molecular weight 65 – 150 kDa and are loaded in macroporous poly(N-isopropylacrylamide) hydrogels, placed episclerally. Polyethylene glycol (PEG) is used as a pore forming agent but does not participate in the polymerization / crosslinking. The gels are known to show a pronounced and reversible temperature-induced phase transition at a lower critical solution temperature, LCST, about 32oC. The phase transition entails change in the hydrophilic / hydrophobic character of the material which results in gel swelling below LCST and gel collapse above LCST. Based on the gel composition, and PEG concentration and molecular weight, the degree of equilibrium swelling is calculated. When the gel is placed episclerally, its temperature, degree of swelling and amount of drug loaded are known. The gel is modeled as a poroelastic medium The dynamics of the drug release are obtained from the solution of the following equations: (a) heat equation (to predict evolution of the gel temperature from its initial value to the body temperature), (b) mass balance for the system of the poroelastic medium and fluid (water), (c) individual momentum balances for the poroelastic medium and the fluid, and (d) mass balance for the anti-VEGF agent.

The model of anti-VEGF agent release from the episcleral hydrogel impant is followed by a pharmacokinetic model with three compartments, i.e., sclera, choroid, retina, for transport of the anti-VEGF agent through the posterior eye tissue. The concentration of the anti-VEGF agents released from the impant is the incoming concentration of the drug in the sclera. From the three compartments, the sclera has the lowest and the retina the highest permeability to macromolecular anti-VEGF agents. The permeability of the sclera to these macromolecules is estimated by the Stokes-Einstein equation and effective medium theories and is found to compare well with measured values. Part of the drug is eliminated in the sclera and the choroid by vascular microflows. The pharmacokinetic model provides us with estimates of duration of the sustained drug release and the times of keeping a therapeutic level of the drug at the blood-retina barrier. These estimates will enable us to design more efficacious hydrogel implants for sustained delivery of anti-VEGF agents to the blood-retina barrier.