Large-pore silica nanocarriers for antiangiogenic treatment against age-related macular degeneration

Background: Wet age-related macular degeneration (AMD) is a progressive disease that leads to central vision loss due to damaged retinal pigment epithelium (RPE) and photoreceptors in the central area of the retina. Wet AMD occurs in patients who develop subretinal choroidal neovascularization, mostly produced by an abnormal expression in the RPE of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues such as important side effects and low patient compliance. The encapsulation of anti-VEGF drugs in suitable nanocarriers with better penetration, higher retention times and sustained release would be of great interest. The objective of this work is the development of a drug delivery system for the topical administration of anti-VEGF siRNA molecules based on large-pore mesoporous silica nanoparticles (LP-MSNs). siRNA is loaded into the LP-MSNs pores, while the nanoparticles’ external surface is functionalized with polyethylenimine (PEI) chains, which act as pore capping ensembles that allow the siRNA controlled release and promote endosomal escape to facilitate its cytosolic delivery.