Microwave Assisted Solvent Anti-Solvent Approach for The Development of Melatonin Loaded Nano-Formulation to Improve Neuroprotective Activity

Abstract

Melatonin has emerged as a promising neuroprotective agent for treating various neurological disorders, yet its clinical application remains limited due to poor bioavailability, rapid metabolism, and short half-life. This research develops a novel microwave-assisted solvent anti-solvent Nano formulation to enhance melatonin's neuroprotective efficacy. The study addresses critical challenges in conventional melatonin delivery by creating nanoparticles that improve brain bioavailability and sustained release characteristics. Using microwave irradiation to accelerate the solvent anti-solvent precipitation process, we synthesized melatonin-loaded nanoparticles with mean particle sizes ranging from 120-180 nm and encapsulation efficiencies exceeding 78%. The Nano formulation demonstrated significantly enhanced cellular uptake in neuronal cell lines, improved stability under physiological conditions, and superior neuroprotective effects against oxidative stress-induced neuronal damage compared to free melatonin. In vitro studies showed that the Nano formulation reduced reactive oxygen species generation by 65% and prevented neuronal apoptosis more effectively than conventional melatonin solutions. The microwave-assisted approach reduced synthesis time from hours to minutes while maintaining reproducibility and scalability. This work contributes a practical, efficient method for developing melatonin Nano formulations with enhanced therapeutic potential for neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, and traumatic brain injury.