Fabrication of nanoparticulate system for oral delivery of Naringenin against paraquat-induced Parkinson's disorder in Wistar rats

Parkinson's disorder (PD) is a neurodegenerative condition associated with slow movement, tremors, imbalance, bradykinesia, and rigidity with advanced complications like sleep disorder, pains, sensory disability, and cognitive impairment. As per World Health Organization, PD is the leading neurological disorder worldwide. Although Parkinson's disorder cannot be cured, medications might significantly improve the symptoms. Current treatment for Parkinson's disorder includes cell implantation, Gene therapy, Surgical approaches, and Rehabilitation. But there are several adverse effects associated with these treatment methods which can be addressed using nanoparticles that possesses the ability to cross the blood-brain barrier, increased stability against enzymatic degradation, lowers liver toxicity, etc. Several Phyto-constituent have proven their role in the management of Parkinson's disorder. One such natural flavonoid is Naringenin, which is been reported to have diverse neuronal effects. In the first part, the Naringenin-loaded PLGA nanoparticles were fabricated by using a single emulsion solvent emulsion method. Optimization was performed by using a 32-factorial design to investigate the impact of independent variables viz. PLGA concentration and number of HPH cycles. The optimized batch was spray-dried and evaluated for DSC, XRD, and SEM to confirm desired characteristics. LD50 was determine by performing Acute Oral Toxicity (AOT) study as per OECD-420 guidelines. Parkinson was induced by injecting rats with paraquat (i.p.) twice a week for 6 weeks. Simultaneously, nano-suspension and standard drug were also administered orally to respective group 60min prior to paraquat every day for 6 weeks. After 42/45 days parameters like Gross examination of the brain, Relative brain weight determination, behavioral parameters, biochemical evaluation (MDA, SOD, CAT, GSH, α-synuclein protein levels), and immunohistochemistry (BDNF level) investigation were performed. Brain histopathological study was performed to support the findings. An optimized batch of Naringenin-loaded PLGA nanoparticles showed particle size, PDI, and %EE as 162.1 ​nm, 0.288, and 91% respectively. Spray-dried nanoparticles were found to be spherical during SEM analysis which may facilitate the easy movement of nanoparticles through different barriers. The DSC and XRD study confirmed the molecular dispersion of the drug. In vivo studies showed quite promising results through behavioural, histopat