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Iranian Journal of Pharmaceutical Research
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Ambhore, N., Kalidhindi, R., Mulukutla, S., Yamjala, K., Mohire, S., Karri, V., Gupta, S., Murthy, V., Kannan, E. (2017). Brain Targeting of 1,9-Pyrazoloanthrone an c-Jun-N-terminal Kinase Inhibitor Using Liposomes for Effective Management of Parkinson’s Disease. Iranian Journal of Pharmaceutical Research, 16(4), 1463-1478. doi: 10.22037/ijpr.2017.2131
Nilesh Sudhakar Ambhore; Rama Satyanarayana Raju Kalidhindi; Shashank Mulukutla; Karthik Yamjala; Shubhashri Mohire; Veera Venkata Satyanarayana Reddy Karri; saurabh Gupta; Vishakantha Murthy; Elango Kannan. "Brain Targeting of 1,9-Pyrazoloanthrone an c-Jun-N-terminal Kinase Inhibitor Using Liposomes for Effective Management of Parkinson’s Disease". Iranian Journal of Pharmaceutical Research, 16, 4, 2017, 1463-1478. doi: 10.22037/ijpr.2017.2131
Ambhore, N., Kalidhindi, R., Mulukutla, S., Yamjala, K., Mohire, S., Karri, V., Gupta, S., Murthy, V., Kannan, E. (2017). 'Brain Targeting of 1,9-Pyrazoloanthrone an c-Jun-N-terminal Kinase Inhibitor Using Liposomes for Effective Management of Parkinson’s Disease', Iranian Journal of Pharmaceutical Research, 16(4), pp. 1463-1478. doi: 10.22037/ijpr.2017.2131
Ambhore, N., Kalidhindi, R., Mulukutla, S., Yamjala, K., Mohire, S., Karri, V., Gupta, S., Murthy, V., Kannan, E. Brain Targeting of 1,9-Pyrazoloanthrone an c-Jun-N-terminal Kinase Inhibitor Using Liposomes for Effective Management of Parkinson’s Disease. Iranian Journal of Pharmaceutical Research, 2017; 16(4): 1463-1478. doi: 10.22037/ijpr.2017.2131

Brain Targeting of 1,9-Pyrazoloanthrone an c-Jun-N-terminal Kinase Inhibitor Using Liposomes for Effective Management of Parkinson’s Disease

Article 17, Volume 16, Issue 4, Autumn 2017, Page 1463-1478  XML PDF (2.96 MB)
Document Type: Research article
DOI: 10.22037/ijpr.2017.2131
Authors
Nilesh Sudhakar Ambhore email 1; Rama Satyanarayana Raju Kalidhindi2; Shashank Mulukutla2; Karthik Yamjala3; Shubhashri Mohire3; Veera Venkata Satyanarayana Reddy Karri4; saurabh Gupta5; Vishakantha Murthy6; Elango Kannan7
1Dept of Pharmacology, JSS College of Pharmacy, Rockland, Elkhil Road, Ooty. 643001
2Department of Pharmacology, JSS College of Pharmacy, Ootacamund, JSS University, Mysore 643001, India
3Department of Pharmaceutical Analysis, JSS College of Pharmacy, Ootacamund, JSS University, Mysore 643001, India
4Department of Pharmaceutics, JSS College of Pharmacy, Ootacamund, JSS University, Mysore 643001, India
5Department of Pharmacology, Indore Institute of Pharmacy, Pithampur road, Opp. IIM, Rau, Indore, M.P, India
6Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905 – USA
7Department of Pharmacology, JSS College of Pharmacy, Ootacamund, JSS University, Mysore, Tamilnadu-643001, India
Abstract
The major challenge to treat Parkinson’s disease (PD) is penetration of target molecule into the brain to improve the efficacy of drugs. To achieve better brain penetration and targeted delivery, 1,9-Pyrazoloanthrone (1,9-P) loaded liposomes were developed by solvent injection technique using ultrasonication and evaluated for particle size, morphology, entrapment efficiency, FT-IR, and in-vitro drug release studies. The potential of 1,9-Pyrazoloanthrone (1,9-P), a c-Jun-N-terminal Kinase (JNK-3) inhibitor which could stop or retard the rate of apoptosis of neuronal cells was also evaluated. In-vivo pharmacokinetic and brain uptake studies of liposomes were performed to investigate the bioavailability and brain distribution of 1,9-P. Cytotoxicity and neuroprotection were done on SH-SY5Y cell line using MTT and AO/EB apoptosis assay. The optimized batch of liposomes showed an average size of 112.33 ± 0.84 nm with a zeta potential value of -19.40 mV and 78.96 ± 0.28% drug entrapment efficiency. The in-vitro release studies demonstrated the sustained release profile of liposome up to 24 h. The pharmacokinetic data in Wistar rats over the period of 12 h demonstrated 4.82-folds greater AUC (0-12 h) for liposome in brain compared with 1,9-P suspension. Cytotoxicity assay showed no sign of toxicity, whereas apoptosis assay revealed a neuroprotective action of liposomes. The results demonstrated successful targeting of the 1,9-P, to brain as a novel strategy having significant therapeutic potential to treat PD.
Keywords
Parkinson’s disease; 1; 9-Pyrazoloanthrone; Biodistribution; liposomes; Sustained-release system; SH-SY5Y neuroblastoma cell line
Main Subjects
Pharmacutics
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