INTRANASAL DELIVERY OF RESVERATROL AND PIPERINE NANOSTRUCTURED LIPID CARRIERS: SYNERGISTIC NEUROPROTECTION IN A 6-HYDROXYDOPAMINE-INDUCED PARKINSON’S DISEASE RAT MODEL

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, leading to motor and cognitive impairments. This study investigates the neuroprotective potential of intranasally delivered Resveratrol-loaded Nanostructured Lipid Carriers (R-NLC), Piperine-loaded NLC (P-NLC), and their combined formulation (R+P-NLC) in a 6-hydroxydopamine (6-OHDA)-induced PD rat model, compared to intravenous Levodopa. Male Wistar rats were subjected to unilateral 6-OHDA lesions in the substantia nigra or striatum, followed by twice-daily intranasal administration of NLC formulations for three weeks. Behavioral assessments, including Rotarod, Open Field, Grip Strength, Y-Maze, and Morris Water Maze tests, conducted on Days 7, 14, and 21, revealed significant improvements in motor coordination, locomotor activity, fine motor skills, and cognitive function in treated groups compared to the PD group. Biochemical analyses demonstrated restored dopamine levels, reduced glutamate and acetylcholine levels, and improved oxidative stress markers (MDA, SOD, GSH, CAT) in treated groups, with R+P-NLC and Levodopa showing superior efficacy. Histological analysis of the substantia nigra and striatum confirmed significant neuroprotection, with R+P-NLC exhibiting near-normal neuronal morphology, suggesting a synergistic effect of Resveratrol and Piperine. These findings highlight the potential of intranasal NLC delivery as an effective, non-invasive strategy for PD treatment, with the combined R+P-NLC formulation offering promising therapeutic benefits.