Eye drops of Ch-Cx carrier silibinin inducing protection in a model of Age-related Macular Disease (AMD).

AMD is a multifactorial neurodegenerative disease that affects the macula, leading cause of blindness. A pivotal role in AMD pathogenesis is played by dysregulation of iron homeostasis and no effective cure exists; controversial effects are indeed reported by the current treatment with anti-VEGF intraocular injections. An important goal is to obtain effective therapeutic drug concentrations in the eye posterior segment throughout topical drug administration. Due to blood-ocular barriers and lacrimal drainage it is difficult to design a non-invasive ocular formulation. Nanoparticles have gained attention because of their ability to penetrate ocular tissues, enhancing the drug bioavailability. We here propose a novel topical ophthalmic formulation based on choline-calix[4]arene nanoparticles (Ch-Cx) loaded with silibinin (Slb), as a potential treatment for AMD. Slb is a flavonoid extract of silymarin with multiple positive biological activities, also against several neurodegenerative conditions. The Ch-Cx nanoparticle was designed to feature a size smaller than 100 nm, a low polydispersity index and stability, and a positively charged surface that may increase eye adhesion and surface permanence. Using human retinal pigment epithelial cells (ARPE-19) exposed or not to FeSO 4 , and analyzing the effects of a topical ocular application of Ch-Cx- Slb in a AMD-like rat model induced by intravitreal injection of FeSO 4 , we validated our hypothesis. Once daily application of eye drops of Ch-Cx- Slb for ten days resulted in reduction of oxidative stress, inflammation and anti-VEGF proliferation, and effectively protected from RPE/choroid alteration and retinal degeneration in the AMD-like model.