Mechanism of nanotization-mediated improvement in the efficacy of caffeine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism

Naveen Kumar Singhal, Swati Agarwal, Priyanka Bhatnagar, Manindra Nath Tiwari, Shashi Kant Tiwari, Garima Srivastava, Pradeep Kumar, Brashket Seth, Devendra Kumar Patel, Rajnish Kumar Chaturvedi, Mahendra Pratap Singh, Kailash Chand Gupta

Research output: Contribution to journalArticlepeer-review


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-κB) 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-κB and activation of protein kinase B phosphorylation.

Original languageEnglish (US)
Pages (from-to)2211-2222
Number of pages12
JournalJournal of Biomedical Nanotechnology
Issue number12
StatePublished - Dec 1 2015
Externally publishedYes


  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Caffeine
  • Caffeine-encapsulated PLGA nanoparticles
  • Parkinson's disease

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science


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