Paper Title
FUNCTIONALIZED NANOCARRIERS FOR TARGETED DELIVERY OF ROSMARINIC ACID AND RESVERATROL TO ACCUMULATED Α-SYNUCLEIN AGAINST NEURODEGENERATION

Abstract
Abstract - Drug delivery nanocarriers composed of poly(carbonate urethane) and polyvinylpyrrolidone with leptin (Lep) and wheat germ agglutinin (WGA) were develop to carry two antioxidants, rosmarinic acid (RA) and resveratrol (RES), for inhibiting pathobiology in Parkinson’s disease (PD) management. Composition of the polymeric nanoparticles (NPs) were optimized via physical properties, including the average particle diameter and stability, and pharmaceutical properties, including the drug encapsulation and release. The optimal nanocarriers were applied to penetrate the blood-brain barrier (BBB) and to protect 1-methyl-4-phenylpyridinium (MPP+)-insulted SH-SY5Y cells from apoptosis. The viability of BBB cells was in an acceptable range after treating the Lep- and WGA-conjugated NPs with entrapped RA and RES (Lep-WGA-RA-RES-NPs), suggesting a qualified colloidal system with biocompatibility for targeting the brain. The results indicated that an impact of MPP+ increased α-synuclein (α-syn) expression, and the subsequent accumulation of α-syn incited tau protein (tau) phosphorylation in SH-SY5Y cells. Constraint of the inflammatory pathways by Lep-WGA-RA-RES-NPs substantially promoted dopamine transporter (DAT) and B cell lymphoma 2 (Bcl-2) expressions, and decreased Bcl-2-associated X protein (Bax), α-syn, p-tau and caspase-3 expressions in MPP+-insulted SH-SY5Y cells. The dual-functional Lep-WGA-RA-RES-NPs can effectively prevent degenerated dopaminergic neurons from deterioration via restricting abnormal oxidative stress, and can be promising nanocarriers in neuroprotection for PD treatment in preclinical trial. Keywords - Leptin, Wheat Germ Agglutinin, Nanocarrier, Dopaminergic Neuron