Objective: The aim of the present study was to develop and evaluate the neuroprotective effects of resveratrol (RV) using chitosan glutamate nanoparticles (RV-CG-NPs) in a mouse model with MPTP induced Parkinsonism.

Background: Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol. The administration of a neurotoxin in Parkinson’s disease (PD) animal model resulted degeneration of the nigrostriatal dopaminergic (DA) neuron. Further evaluate the neuroprotective effects of resveratrol (RV) using chitosan glutamate nanoparticles (RV-CG-NPs) in a mouse model with MPTP induced Parkinsonism.

Method: The nanoparticles were prepared by ionic gelation method using chitosan and tripolyphosphate, and characterized for particle size distribution, encapsulation efficiency and in vitro drug release. Moreover, the optimized nanoparticles were administered via intranasal route in C57BL/6 mice induced with parkinsonism by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Results: The optimized nanoparticles exhibited particle size of 131 nm, polydispersity index (PDI) of 0.21 and entrapment efficiency of 89%. Pharmacodynamically, MPTP made significant impairment on social recognition memory along with generation of striatal oxidative stress and reduced expression of tyrosine hydroxylase in striatum. Biodistribution study of nanoparticle formulation in brain of C57BL/6 mice showed significantly higher brain levels of resveratrol as compared to the plain resveratrol solution. The Cmax (890.12ng/ml) and AUC (1986.51 ng h/ml) of said optimized nano-formulation (i.n) were found to be significantly higher in the brain at all time points compared to RV solution (i.n) and chitosan glutamate-RV-NPs (i.v). Moreover, the nanoparticles also showed significant neuroprotection activity against MPTP-induced parkinsonism in mice.

Conclusion: Overall, the results from the current work showed enhanced brain levels and neuroprotective effect resveratrol when administered through nanoparticles, which could be a substantial achievement of direct nose-to-brain targeting in Parkinson’s disease.

References: 1. Palle S, Neerati P. Improved neuroprotective effect of resveratrol nanoparticles as evinced by abrogation of rotenone-induced behavioral deficits and oxidative and mitochondrial dysfunctions in rat model of Parkinson’s disease. Naunyn Schmiedebergs Arch Pharmacol. 2018 Apr;391(4):445-453. 2. Mahfoozur Rahman. Rutin as protective and beneficial effect against 6-hydroxydopamine induced Parkinson’s disease model via altered the genetic ackgrounds” Got full travel grant award in IAPRD 2017.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/improving-neuroprotective-effects-of-resveratrol-by-brain-targeting-through-chitosan-glutamate-nanoparticles-in-mptp-induced-parkinsonism/