Computational modeling of drug delivery for treatment of age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a progressive, neurodegenerative ocular disease. It involves cell proliferation and uncontrolled growth in blood vessels leading to leaking of blood and proteins, scarring of the macula region, and, eventually, irreversible loss of vision. Neovascular AMD results from uncontrolled expression of the vascular endothelial growth factor (VEGF) and is treated primarily with the anti-VEGF macromolecular drugs, administered by intravitreal (IVT) injection. A less invasive, less risky system of delivery involves delivery from thermally responsive hydrogels of poly-(N-isopropylacrylamide) (pNIPAm), placed episclerally. In this case, most of the drug load is released by convection, and the remaining, close to 30% by weight, is released by diffusion. It was recently indicated that the chronic exposure to oxidative stress and a decline in lysosomal activity of retinal pigment epithelium (RPE) cells is a possible cause for RPE degeneration. An exogenous delivery of recombinant hHsp70 chaperone protein can protect RPE cells from oxidative stress and thus has the potential to be a therapeutic option against AMD. In this study, delivery of rhHsp70 from an episcleral hydrogel implant has been simulated with an anatomically and physiologically correct model of the human eye. The average drug concentration in sclera, choroid, retina and vitreous is com-pared, when the rhHsp70 is released at the limbus and the posterior of the eye. The results indicate that drug delivery from thermally responsive hydrogels, placed episclerally, is more effective than the currently practiced delivery through IVT injection.