title: Enhancement in the Neuroprotective Power of Riluzole Against Cerebral Ischemia Using a Brain Targeted Drug Delivery Vehicle.
abstract: Riluzole is the only available drug for motor neuron diseases quite well-known for its neuroprotective activity. But its poor aqueous solubility, short half-life with some side-effects at higher concentration poses a limitation to its use as a therapeutic agent. The present study was performed to investigate the therapeutic potential of nanoriluzole (NR), i.e., riluzole encapsulated in nanoparticles against cerebral ischemia (stroke) at three different concentrations [10 (NRL), 20 (NRM), and 40 (NRH) μg/kg body weight intraperitoneally (i.p.)]. Chitosan conjugated NIPAAM (N-isopropylacrylamide) nanoparticles coated with tween80 were synthesized through free radical polymerization. The particles were characterized with Transmission Electron Microscopy, Dynamic Light Scattering, and Fourier Transform Infrared spectroscopy and were found to have size of ∼50 nm. Cerebral ischemia was induced by Middle Cerebral Artery Occlusion (MCAO) model for 1 h and NR was given intraperitoneally after 1 h of MCAO. Animals were dissected after a reperfusion period of 24 h for evaluation of various parameters. Triphenyl tetrazolium chloride staining shows substantial reduction in infarct size in all three treated groups. It was also supported by histopathological results, biochemical parameters, and behavioral studies. Immunological parameters like NOS-2, NF-kB, and COX-2 also show profound reduction in expression in NR treated groups. Thus, the present work clearly demonstrated that the nanoparticle was good enough to carry large amount of drug across the Blood Brain Barrier which results in significant neuroprotection even at a very low concentration. It also substantially lowered the required concentration by overcoming the poor aqueous solubility; hence hardly leaving any scope for side-effects.
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi-62 110062, India.
authors.forename: Shashi K
authors.initials: SK
authors.lastname: Verma
authors.affiliation: Department of Biomedical Sciences, Shaheed Rajguru College of Applied Sciences for Women, Delhi University , Delhi-7 110062, India.
authors.forename: Indu
authors.initials: I
authors.lastname: Arora
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi-62 110062, India.
authors.forename: Kalim
authors.initials: K
authors.lastname: Javed
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University) , New Delhi-62 110062, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Akhtar
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi-62 110062, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Samim
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D016503:Drug Delivery Systems; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole
keywords: BBB; nanoparticle; neuroprotection; riluzole; stroke