For some instances of
Parkinson disease (PD), current evidence in the literature is consistent with
reactive oxygen species being involved in the etiology of the disease. The management of PD is still challenging owing to its ambiguous etiology and lack of permanent cure. Because
nicotine offers neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced
parkinsonism, the neuroprotective efficacy of
nicotine-encapsulated
poly(lactic-co-glycolic) acid (PLGA) nanoparticles and the underlying mechanism of improved efficacy, if any, over bulk
nicotine were assessed in this study. The selected indicators of oxidative stress, dopaminergic neurodegeneration and apoptosis, were measured in both in vitro and rodent models of
parkinsonism in the presence or absence of "nanotized" or bulk
nicotine. The levels of
dopamine and its metabolites were measured in the striatum,
nicotine and its metabolite in the nigrostriatal tissues while the immunoreactivities of
tyrosine hydroxylase (TH),
metallothionein-III (
MT-III),
inducible nitric oxide synthase (iNOS) and microglial activation were checked in the substantia nigra of controls and treated mice. GSTA4-4,
heme oxygenase (HO)-1,
tumor suppressor protein 53 (p53),
caspase-3, lipid peroxidation (LPO), and
nitrite levels were measured in the nigrostriatal tissues.
Nicotine-encapsulated PLGA nanoparticles improved the endurance of TH-immunoreactive neurons and the number of fiber outgrowths and increased the
mRNA expression of TH, neuronal
cell adhesion molecule, and growth-associated protein-43 over bulk against 1-methyl-4-phenyl pyridinium ion-induced degeneration in the in vitro model.
MPTP reduced TH immunoreactivity and levels of
dopamine and its metabolites and increased microglial activation, expression of GSTA4-4, iNOS,
MT-III, HO-1, p53, and
caspase-3, and levels of
nitrite and LPO. Whereas both bulk
nicotine and
nicotine-encapsulated PLGA nanoparticles modulated the changes toward controls, the modulation was more pronounced in
nicotine-encapsulated PLGA nanoparticle-treated parkinsonian mice. The levels of
nicotine and
cotinine were elevated in
nicotine-encapsulated PLGA nanoparticle-treated PD mouse brain compared with bulk. The results obtained from this study demonstrate that nanotization of
nicotine improves neuroprotective efficacy by enhancing its bioavailability and subsequent modulation in the indicators of oxidative stress and apoptosis.