Melatonin and the nervous system: nanomedicine perspectives

The mechanism of action of melatonin on the nervous system, sleep, cognitive deficits, and aging is not fully understood. Neurodegenerative diseases (ND) are one of the leading causes of disability and mortality worldwide. Sleeping and cognitive impairments also represent common and serious public health problems, particularly deteriorating with the aging process. Melatonin, as a neuromodulatory hormone, regulates circadian rhythms and the sleep-wake cycle, with functions extending to antioxidant, anti-inflammatory, neuroprotective, and anti-aging properties. However, melatonin is a hydrophobic compound with relatively low water solubility and a short half-life. While melatonin can cross the blood-brain barrier, exogenous melatonin administered orally or intravenously has poor bioavailability, undergoes rapid metabolism in the circulation, and shows limited brain accumulation, ultimately compromising its therapeutic efficacy. In recent years, the convergence of melatonin research with nanomedicine ensures safe therapeutic uses, limited drug degradation, and perspectives for targeted drug delivery to the central nervous system. Here we outline the promising neurotherapeutic properties of nanomaterials as carriers loaded with melatonin drug alone or in combinations with other active molecules.