The effect of safranal loaded mucoadhesive nanoemulsion on oxidative stress markers in cerebral ischemia.
Antioxidants, with reported neuroprotective activity, encounter free radical induced neural damage leading to reduced risk of cerebral ischemia-reperfusion (IR) injury. Safranal, an antioxidant drug with potential role in the amelioration of cerebral ischemia, endures low solubility and poor absorption property thus resulting a low serum and tissue bioavailability. This research aims to prepare nanoemulsion with the concept; to increase the bioavailability in order to reduce oxidative stress-induced brain injury as well as to evaluate the brain-drug targeting following non-invasive nasal route administration in middle cerebral artery occlusion (MCAO) animal model. Titration method was used to prepare safranal mucoadhesive nanoemulsion (SMNE) followed by further characterization, i.e. entrapment efficiency, particles size, and zeta potential study. Optimized SMNE showed; mean globule size of 89.64 nm (±9.12), zeta potential -11.39 mV (±1.32), drug content 98.47% (±1.01), and viscosity of 124 cp (±14). Rats were subjected to 2 h of MCAO, successively followed by a 22 h reperfusion, after which the grip strength, locomotor activity, and biochemical studies, i.e. glutathione reductase (GR), glutathione peroxidase, lipid peroxidation, catalase, and superoxide dismutase were studied as assessment tool for effective treatment in brain. SMNE administered i.n. (intranasal) in MCAO induced cerebral ischemia rats exhibited significant improvement in neurobehavioral (locomotor and grip strength) and antioxidant activity as well as histopathological studies. The toxicity studies performed at the end revealed safe nature of developed SMNE.
a Department of Pharmaceutics, College of Clinical Pharmacy , Dammam University , Dammam , Kingdom of Saudi Arabia.
Niyaz
N
Ahmad
b Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy , Dammam University , Dammam , Kingdom of Saudi Arabia.
Rizwan
R
Ahmad
c Department of Pharmacy Practice, College of Clinical Pharmacy , University of Dammam , Dammam , Kingdom of Saudi Arabia.
Atta
A
Abbas Naqvi
d Neuroscience and Toxicology Unit , College of Pharmacy, Jazan University , Jazan , Kingdom of Saudi Arabia.
Mohammad
M
Ashafaq
e Department of Pharmaceutics, School of Medical and Allied Sciences , Galgotias University , Gautam Budh Nagar , Greater , Noida , India.
Md Aftab
MA
Alam
f Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy , Hamdard Nagar , Jamia Hamdard , New Delhi , India.
Farhan Jalees
FJ
Ahmad
g Department of Pharmacology, College of Clinical Pharmacy , University of Dammam , Dammam , Kingdom of Saudi Arabia.
Mastour Safer
MS
Al-Ghamdi
D000268:Adhesiveness; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D053138:Cyclohexenes / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004655:Emulsions; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D018737:Hand Strength / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008124:Locomotion / Q000187:drug effects; D049329:Nanostructures; D009297:Nasal Mucosa / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D053138:Cyclohexenes; D004655:Emulsions; D013729:Terpenes; D017392:Thiobarbituric Acid Reactive Substances; C087963:safranal; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione
MCAO; Safranal; cerebral ischemia; mucoadhesive nanoemulsion; oxidative stress