Humanin nanoparticles for reducing pathological factors characteristic of age-related macular degeneration

Background: Humanin is a novel neuronal peptide that has displayed potential in the treatment of Alzheimer’s Disease through the suppression of inflammatory IL-6 cytokine receptors. Such receptors are found throughout the body, including the eye, suggesting its other potential applications. Age-related Macular Degeneration (AMD) is the leading cause of blindness in the developing world. There is no cure for this disease, and current treatments have several negative side effects associated with them, making finding other treatment options desirable. Objective: In this study, the potential applications in treating AMD for a more potent humanin derivative, AGA-HNG, were studied. Methods: AGA-HNG was synthesized and encapsulated in chitosan Nanoparticles (NPs), which were then characterized for their size, Encapsulation Efficiency (EE), and drug release. Their ability to suppress VEGF secretion and protect against oxidative apoptosis was studied in vitro using ARPE-19 cells. The chitosan NPs exhibited similar anti-VEGF properties and oxidative protection as the free protein while exhibiting superior pharmaceutical characteristics including biocompatibility and drug release. Results: Drug-loaded NPs exhibited a radius of 346nm with desirable pharmacokinetic properties including a stable surface charge (19.5 ± 3.7 mV) and steady drug release capacity. AGA-HNG showed great promise in mediating apoptosis in hypoxic cells. They were also able to significantly reduce VEGF expression in vitro with reduced cellular toxicity compared to the free drug. Conclusion: The ability of this drug delivery system to reduce retinal apoptosis with desirable pharmacokinetic and biocompatible properties makes this a promising therapeutic option for AMD.