Mechanism of Nanotization-Mediated Improvement in the Efficacy of Caffeine Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonism
Authors: Priyanka Bhatnagar
Devendra Kumar Patel
Swati Agarwal
Rajnish Kumar Chaturvedi
Pradeep Kumar
Manindra Nath Tiwari
Shashi Kant Tiwari
Garima Srivastava
Kailash Chand Gupta
Mahendra Pratap Singh
Naveen Kumar Singhal
Seth Brashket
Journal: Journal of Biomedical Nanotechnology (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: neuroprotective efficacy; caffeine-encapsulated PLGA nanoparticles; Parkinsonism; dopaminergic neurons; tyrosine hydroxylase

Abstract:  The study aimed to measure the neuroprotective efficacy of caffeine-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles over bulk and to delineate the mechanism of improvement in efficacy both in vitro and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinsonism. Caffeine-encapsulated PLGA nanoparticles exhibited more pronounced increase in the endurance of dopaminergic neurons, fibre outgrowth and expression of tyrosine hydroxylase (TH) and growth-associated protein-43 (GAP-43) against 1-methyl-4-phenylpyridinium (MPP+)-induced alterations in vitro. Caffeine-encapsulated PLGA nanoparticles also inhibited MPP(+)-mediated nuclear translocation of nuclear factor-kappa B (NF-Œ∫B) and augmented protein kinase B phosphorylation more potentially than bulk counterpart. Conversely, MPTP reduced the striatal dopamine and its metabolites and nigral TH immunoreactivity whereas augmented the nigral microglial activation and nigrostriatal lipid peroxidation and nitrite content, which were shifted towards normalcy by caffeine. The modulations were more evident in caffeine-encapsulated PLGA nanoparticles treated animals as compared with bulk. Moreover, the striatal caffeine and its metabolites were found to be significantly higher in caffeine-encapsulated PLGA nanoparticles-treated mice as compared with bulk. The results thus suggest that nanotization improves the protective efficacy of caffeine against MPTP-induced Parkinsonism owing to enhanced bioavailability, inhibition of the nuclear translocation of NF-Œ∫B and activation of protein kinase B phosphorylation. 

Retracted: No

PubPeer comments:
  Figure 3. Dopaminergic neuron cultures were treated with bulk caffeine or caffeine-encapsulated PLGA nanoparticles (50 M) in the presence or absence of MPP+ (100 M). GAP-43 immunoreactivity in cultured dopaminergic neurons of various treatment groups; scale bar = 20 m (A).  Overlapping images representing different conditions. , 
 J Biomed Nanotechnol. 2019 Jan 1;15(1):212-213. doi: 10.1166 jbn.2019.2662. ERRATUM Mechanism of Nanotization-Mediated Improvement in the Efficacy of Caffeine Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonism (Journal of Biomedical Nanotechnology, Vol. 11(12), pp. 2211-2222 (2015)). Singhal NK, Agarwal S, Bhatnagar P, Tiwari MN, Tiwari SK, Srivastava G, Kumar P, Seth B, Patel DK, Chaturvedi RK, Singh MP, Gupta KC. Erratum for Mechanism of Nanotization-Mediated Improvement in the Efficacy of Caffeine Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonism. [J Biomed Nanotechnol. 2015] ,