Melatonin-Polydopamine Nanoformulation Prevents Retinal Neurodegeneration in a Preclinical Model of Diabetic Retinopathy

Reactive oxygen species, inflammation, angiogenesis, and retinal neurodegeneration lead to diabetic retinopathy (DR) progression. The inhibition of VEGF and prevention from retinal neurodegeneration pave the way to developing DR treatment. Melatonin is a potent anti-inflammatory agent and a promising therapeutic candidate for DR therapy. However, melatonin has a lower absorption kinetic that limits its therapeutic efficiency. Recently, nanotechnology-based nanodrug delivery systems have gained attention to overcome limitations of existing potent drugs. Therefore, we have prepared melatonin-loaded polydopamine nanoparticles to improve the melatonin release profile that result in endowed therapeutic potential of melatonin. The evaluation of in vitro and in vivo DR studies have shown the protection efficiency of our nanoformulation. The mechanism of protection is attributed to downregulated vascular endothelial growth factor (VEGF), inhibited CASPASE3, and upregulated nerve/glial antigen 2 (NG2) and choline acetyltransferase (CHAT) that reflect the antiangiogenesis, antiapoptosis, and neuroprotective potential of our nanoformulation in the preclinical DR model. Thus, the antiangiogenesis and retinal neuroprotection efficiency of melatonin-loaded polydopamine nanoparticles suggests our nanoformulation as a promising nanotherapeutic agent for DR treatment.