title: Quantification and evaluation of thymoquinone loaded mucoadhesive nanoemulsion for treatment of cerebral ischemia.
abstract: Stroke is an important cause of deaths worldwide, resulting in an irreversible deterioration of the central nervous system. Finally, production of more free radicals. Therefore, Thymoquinone is having antioxidant property and reported to have a potential role in the amelioration of cerebral ischemia but due to low solubility and poor absorption; they exhibit low serum and tissue levels. Present work aims to prepare nanoemulsions in order enhance the bioavailability of drug and hence evaluate the drug targeting in brain via non-invasive nasal route administration. Thymoquinone Mucoadhesive Nanoemulsion (TMNE) was prepared by ionic gelation method; characterized for particles size, entrapment efficiency, zeta potential, and ex vivo permeation study. Optimized TMNE ended up with a mean globule size 94.8±6.61nm; zeta potential -13.5±1.01mV; drug content 99.86±0.35% and viscosity 110±12cp. Ultra Performance Liquid Chromatography-Photodiode Array (UPLC-PDA) based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (628.5786±44.79%) and brain drug-targeting potential (89.97±2.94%) studies via post intranasal administration which revealed enhanced bioavailability of TQ in brain as compared to intravenous administration. Improved neurobehavioural activity (locomotor and grip strength) was observed in middle cerebral artery occlusion induced cerebral ischemic rats after i.n. administration of TMNE.
authors.affiliation: Department of Pharmaceutics, College of Clinical Pharmacy, University of Dammam, Dammam 31441, Saudi Arabia. Electronic address: nanhussain@uod.edu.sa.
authors.forename: Niyaz
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, University of Dammam, Dammam 31441, Saudi Arabia.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Gautam Budh Nagar, Greater Noida 201310, India.
authors.forename: Md Aftab
authors.initials: MA
authors.lastname: Alam
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Samim
authors.affiliation: Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D016227:Benzoquinones / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D054059:Coronary Occlusion / Q000473:pathology; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D008297:Male; D020768:Middle Cerebral Artery / Q000601:surgery; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D016227:Benzoquinones; D004337:Drug Carriers; D004655:Emulsions; D018696:Neuroprotective Agents; C003466:thymoquinone
keywords: Brain pharmacokinetics; Cerebral ischemia; Nanoemulsion; Thymoquinone; UPLC-PDA method validation