Rutin-encapsulated chitosan nanoparticles targeted to the brain in the treatment of Cerebral Ischemia.
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.).


RESULTS
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.


CONCLUSIONS
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.
Department of Pharmaceutics, College of Clinical Pharmacy, Dammam University, Dammam 31441, Saudi Arabia. Electronic address: nanhussain@uod.edu.sa.
Niyaz
N
Ahmad
Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Dammam University, Dammam 31441, Saudi Arabia.
Rizwan
R
Ahmad
Department of Pharmacy Practice, College of Clinical Pharmacy, University of Dammam, Dammam 31441, Saudi Arabia.
Atta Abbas
AA
Naqvi
Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Gautam Budh Nagar, Greater Noida 201310, India.
Md Aftab
MA
Alam
Neuroscience and Toxicology Unit, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
Mohammad
M
Ashafaq
Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110062, India.
Mohd
M
Samim
Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
Zeenat
Z
Iqbal
Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
Farhan Jalees
FJ
Ahmad
D000268:Adhesiveness; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D000067493:Dynamic Light Scattering; D006041:Goats; D018737:Hand Strength; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009297:Nasal Mucosa / Q000187:drug effects; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D010919:Placebos; D011108:Polymers / Q000737:chemistry; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012431:Rutin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution / Q000187:drug effects
D010919:Placebos; D011108:Polymers; D012431:Rutin; D048271:Chitosan
Brain pharmacokinetics and pharmacodynamics; Cerebral ischemia; Chitosan nanoparticles; Rutin; UPLC–MS/MS method validation