Phytosome-Based Delivery of Andrographolide Enhances Neuroprotection In Experimental Models of Parkinson’s Disease

Parkinson's disorder (PD) is a progressive neurodegenerative condition characterized by oxidative stress and loss of dopaminergic neurons, for which current pharmacological treatments provide only symptomatic relief and are associated with long-term complications. This study investigated the neuroprotective potential of Andrographolide-Loaded Phytosomes (AGP) as a cutting-edge medication delivery method to improve the bioavailability and the effectiveness of Andrographolide in experimental PD models. AGPs were prepared by solvent evaporation using varying drug-to-lecithin ratios and evaluated for drug content, efficiency of entrapment, zeta potential, and particle size. The optimized formulation (1:1 ratio) exhibited a particle size of 227.4 nm, a zeta potential of –33.3 mV, and an entrapment efficiency of 76%, confirming the formation of stable vesicular structures. In vivo, rotenone-induced PD rat models were used to assess motor and cognitive functions, biochemical parameters, and histopathology. AGP treatment significantly improved motor performance in pole, rotarod, grip strength, stair, and wire-hanging tests, while also restoring antioxidant defenses and reducing lipid peroxidation. Moreover, AGP markedly decreased restored dopamine levels, and preserved mid brain neuronal integrity. Compared to free AGP. Histopathological analysis further confirmed neuroprotection with reduced neuronal degeneration. These findings demonstrate that AGP amplifies its remedial potential by overcoming its poor bioavailability, providing significant neuroprotection and functional recovery in PD models. AGP may serve as a promising natural product-based approach to treating Parkinson's illness.