Assessment and evaluation of melatonin loaded PLGA injectable nanosuspension for the treatment of subarachnoid hemorrhage: Preclinical study

Oxidative stress has connection in the development of acute brain injury after SAH, according to a large body of research. Strong antioxidant melatonin is non-toxic and readily crosses the blood-brain barrier when converted to nanoparticles with PLGA. Nanosuspension of melatonin was formulated by use of different concentrations of PLGA and other stabilisers with variable concentration. Nano particles of Melatonin were prepared by high pressure homogenization method. Their particle size, PDI, zeta potential, surface morphology, encapsulation efficiency and in vitro release study were evaluated. Animal study was performed on rats on different groups. Out of nine batches, formulation F6 was optimized batch with drug: PLGA concentration was 1:3 and Poloxamer 188 was used as stabilizer. Physicochemical parameters for the nanoparticles were found within limit. Drug release was found in sustain release pattern for F6 batch complete release of the drug was observed in 120 hours and showed sustained release of the drug. A considerable decrease in 24-hour mortality was observed in the optimised batch when 30 mg/kg of melatonin was administered. The melatonin therapy group's brain water content was assessed to determine whether a decrease in brain edema was linked to a lower death rate and the prevention of edema and cerebral water content was discovered. Melatonin in a medication delivery system nanocapsulated could be a promising treatment for subarachnoid haemorrhage.