Niyaz Ahmad1,2, Rizwan Ahmad3, Atta Abbas Naqvi4, Md Aftab Alam5, Mohammad Ashafaq6, Rehan Abdur Rub7, Farhan Jalees Ahmad7. 1. a Department of Pharmaceutics, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University (Formerly University of Dammam) , Dammam , Kingdom of Saudi Arabia. 2. b Department of Pharmaceutical Chemistry, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University (Formerly University of Dammam) , Dammam , Kingdom of Saudi Arabia. 3. c Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University (Formerly University of Dammam) , Dammam , Kingdom of Saudi Arabia. 4. d Department of Pharmacy Practice, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University (Formerly University of Dammam) , Dammam , Kingdom of Saudi Arabia. 5. e Department of Pharmaceutics, School of Medical and Allied Sciences , Galgotias University , Greater Noida , India. 6. f Neuroscience and Toxicology Unit, College of Pharmacy , Jazan University , Jazan , Saudi Arabia. 7. g Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India.
Abstract
BACKGROUND: Quercetin (QUR), as an antioxidant flavonoid, exhibits potential role in the amelioration of cerebral ischaemia; however, poor solubility as well as oral absorption results low serum and tissue levels for this drug. PURPOSE OF THE STUDY: To enhance bioavailability, this study aims to prepare QUR nanoemulsions and administer via non-invasive nasal route in order to evaluate the drug targeting in brain. METHODS: Quercetin mucoadhesive nanoemulsion (QMNE) was prepared (ionic gelation method) and optimized using various parameters, that is, particle size, entrapment efficiency, zeta potential and ex vivo permeation study. RESULTS: The results observed for optimized QMNE were as follows: mean globule size (91.63 ± 4.36 nm), zeta potential (-17.26 ± 1.04 mV), drug content (99.84 ± 0.34%) and viscosity (121 ± 13 cp). To evaluate the extent of bioavailability for QMNE via post-intranasal (i.n.) administration, Ultra performance liquid chromatography-mass spectroscopy (UPLC-ESI-Q-TOF-MS/MS)-based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (9333.33 ± 39.39%) and brain drug-targeting potential (2181.83 ± 5.69%) which revealed enhanced QUR brain bioavailability as compared to intravenous administration (i.v.). Furthermore, improved neurobehavioral activity (locomotor and grip strength), histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic rats model after i.n. administration of QMNE. CONCLUSION: This study supports a significant role for QMNE in terms of high brain-targeting potential and formulation efficiency due to ease of access and effective targeting in brain.
BACKGROUND:Quercetin (QUR), as an antioxidant flavonoid, exhibits potential role in the amelioration of cerebral ischaemia; however, poor solubility as well as oral absorption results low serum and tissue levels for this drug. PURPOSE OF THE STUDY: To enhance bioavailability, this study aims to prepare QUR nanoemulsions and administer via non-invasive nasal route in order to evaluate the drug targeting in brain. METHODS:Quercetin mucoadhesive nanoemulsion (QMNE) was prepared (ionic gelation method) and optimized using various parameters, that is, particle size, entrapment efficiency, zeta potential and ex vivo permeation study. RESULTS: The results observed for optimized QMNE were as follows: mean globule size (91.63 ± 4.36 nm), zeta potential (-17.26 ± 1.04 mV), drug content (99.84 ± 0.34%) and viscosity (121 ± 13 cp). To evaluate the extent of bioavailability for QMNE via post-intranasal (i.n.) administration, Ultra performance liquid chromatography-mass spectroscopy (UPLC-ESI-Q-TOF-MS/MS)-based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (9333.33 ± 39.39%) and brain drug-targeting potential (2181.83 ± 5.69%) which revealed enhanced QUR brain bioavailability as compared to intravenous administration (i.v.). Furthermore, improved neurobehavioral activity (locomotor and grip strength), histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO)-induced cerebral ischemicrats model after i.n. administration of QMNE. CONCLUSION: This study supports a significant role for QMNE in terms of high brain-targeting potential and formulation efficiency due to ease of access and effective targeting in brain.
Authors: Amit Alexander; Mukta Agrawal; Ajaz Uddin; Sabahuddin Siddique; Ahmed M Shehata; Mahmoud A Shaker; Syed Ata Ur Rahman; Mohi Iqbal M Abdul; Mohamed A Shaker Journal: Int J Nanomedicine Date: 2019-07-30