Niyaz Ahmad1, Rizwan Ahmad2, Atta Abbas Naqvi3, Md Aftab Alam4, Mohammad Ashafaq5, Mohd Samim6, Zeenat Iqbal7, Farhan Jalees Ahmad7. 1. Department of Pharmaceutics, College of Clinical Pharmacy, Dammam University, Dammam 31441, Saudi Arabia. Electronic address: nanhussain@uod.edu.sa. 2. Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Dammam University, Dammam 31441, Saudi Arabia. 3. Department of Pharmacy Practice, College of Clinical Pharmacy, University of Dammam, Dammam 31441, Saudi Arabia. 4. Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Gautam Budh Nagar, Greater Noida 201310, India. 5. Neuroscience and Toxicology Unit, College of Pharmacy, Jazan University, Jazan, Saudi Arabia. 6. Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110062, India. 7. Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
Abstract
OBJECTIVE: Rutin, a potent antioxidant, has been reported to reduce the risk of ischemic disease. Our study aims to prepare rutin-encapsulated-chitosan nanoparticles (RUT-CS-NPs) via ionic gelation method and determine its results, based on different parameters i.e. surface morphology characterization, in-vitro or ex-vivo release, dynamic light scattering and differential scanning calorimetry (DSC), for treating cerebral ischemia. METHODS: UPLC-ESI-Q-TOF-MS/MS was used to evaluate the optimized RT-CS-NPs1 for brain-drug uptake as well as to follow-up the pharmacokinetics, bio-distrbution, brain-targeting efficiency and potential after intranasal administration (i.n.). KEY FINDINGS: A particle size of <100nm for the formulation, significantly affected by drug:CS ratio, and entrapment efficiency and loading capacity of 84.98%±4.18% and 39.48%±3.16%, respectively were observed for RUT. Pharmacokinetics, bio-distribution, brain-targeting efficiency (1443.48±39.39%) and brain drug-targeting potential (93.00±5.69%) showed enhanced bioavailability for RUT in brain as compared to intravenous administration. In addition; improved neurobehavioral activity, histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO) induced cerebral ischemic rats model after i.n. administration of RUT-CS-NPs. CONCLUSION: A significant role of mucoadhesive-RT-CS-NPs1 as observed after high targeting potential and efficiency of the formulation prove; RUT-CS-NPs are more effectively accessed and target easily the brain.
OBJECTIVE:Rutin, a potent antioxidant, has been reported to reduce the risk of ischemic disease. Our study aims to prepare rutin-encapsulated-chitosan nanoparticles (RUT-CS-NPs) via ionic gelation method and determine its results, based on different parameters i.e. surface morphology characterization, in-vitro or ex-vivo release, dynamic light scattering and differential scanning calorimetry (DSC), for treating cerebral ischemia. METHODS: UPLC-ESI-Q-TOF-MS/MS was used to evaluate the optimized RT-CS-NPs1 for brain-drug uptake as well as to follow-up the pharmacokinetics, bio-distrbution, brain-targeting efficiency and potential after intranasal administration (i.n.). KEY FINDINGS: A particle size of <100nm for the formulation, significantly affected by drug:CS ratio, and entrapment efficiency and loading capacity of 84.98%±4.18% and 39.48%±3.16%, respectively were observed for RUT. Pharmacokinetics, bio-distribution, brain-targeting efficiency (1443.48±39.39%) and brain drug-targeting potential (93.00±5.69%) showed enhanced bioavailability for RUT in brain as compared to intravenous administration. In addition; improved neurobehavioral activity, histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO) induced cerebral ischemicrats model after i.n. administration of RUT-CS-NPs. CONCLUSION: A significant role of mucoadhesive-RT-CS-NPs1 as observed after high targeting potential and efficiency of the formulation prove; RUT-CS-NPs are more effectively accessed and target easily the brain.
Authors: Laurie E Hopkins; Emilia A Laing; Janice L Peake; Dale Uyeminami; Savannah M Mack; Xueting Li; Suzette Smiley-Jewell; Kent E Pinkerton Journal: Toxicol Pathol Date: 2017-09-15 Impact factor: 1.902