PMID- 27264648 OWN - NLM STAT- MEDLINE DCOM- 20170306 LR - 20170306 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) VI - 91 DP - 2016 Oct TI - Rutin-encapsulated chitosan nanoparticles targeted to the brain in the treatment of Cerebral Ischemia. PG - 640-55 LID - S0141-8130(16)30527-X [pii] LID - 10.1016/j.ijbiomac.2016.06.001 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Ahmad, Niyaz AU - Ahmad N AD - Department of Pharmaceutics, College of Clinical Pharmacy, Dammam University, Dammam 31441, Saudi Arabia. Electronic address: nanhussain@uod.edu.sa. FAU - Ahmad, Rizwan AU - Ahmad R AD - Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Dammam University, Dammam 31441, Saudi Arabia. FAU - Naqvi, Atta Abbas AU - Naqvi AA AD - Department of Pharmacy Practice, College of Clinical Pharmacy, University of Dammam, Dammam 31441, Saudi Arabia. FAU - Alam, Md Aftab AU - Alam MA AD - Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Gautam Budh Nagar, Greater Noida 201310, India. FAU - Ashafaq, Mohammad AU - Ashafaq M AD - Neuroscience and Toxicology Unit, College of Pharmacy, Jazan University, Jazan, Saudi Arabia. FAU - Samim, Mohd AU - Samim M AD - Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110062, India. FAU - Iqbal, Zeenat AU - Iqbal Z AD - Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India. FAU - Ahmad, Farhan Jalees AU - Ahmad FJ AD - Nanomedicine Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India. LA - eng PT - Journal Article DEP - 20160602 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 RN - 0 (Placebos) RN - 0 (Polymers) RN - 5G06TVY3R7 (Rutin) RN - 9012-76-4 (Chitosan) SB - IM MH - Adhesiveness MH - Animals MH - Biological Transport/drug effects MH - Brain/drug effects/*pathology MH - Brain Ischemia/*drug therapy/pathology MH - Calorimetry, Differential Scanning MH - Chitosan/*chemistry MH - Chromatography, High Pressure Liquid MH - *Drug Delivery Systems MH - Dynamic Light Scattering MH - Goats MH - Hand Strength MH - Nanoparticles/*chemistry/ultrastructure MH - Nasal Mucosa/drug effects MH - Particle Size MH - Permeability/drug effects MH - Placebos MH - Polymers/chemistry MH - Rats, Wistar MH - Reproducibility of Results MH - Rutin/pharmacokinetics/pharmacology/*therapeutic use MH - Spectrometry, Mass, Electrospray Ionization MH - Tandem Mass Spectrometry MH - Tissue Distribution/drug effects OTO - NOTNLM OT - Brain pharmacokinetics and pharmacodynamics OT - Cerebral ischemia OT - Chitosan nanoparticles OT - Rutin OT - UPLC-MS/MS method validation EDAT- 2016/06/07 06:00 MHDA- 2017/03/07 06:00 CRDT- 2016/06/07 06:00 PHST- 2016/05/10 00:00 [received] PHST- 2016/06/01 00:00 [revised] PHST- 2016/06/01 00:00 [accepted] PHST- 2016/06/07 06:00 [entrez] PHST- 2016/06/07 06:00 [pubmed] PHST- 2017/03/07 06:00 [medline] AID - S0141-8130(16)30527-X [pii] AID - 10.1016/j.ijbiomac.2016.06.001 [doi] PST - ppublish SO - Int J Biol Macromol. 2016 Oct;91:640-55. doi: 10.1016/j.ijbiomac.2016.06.001. Epub 2016 Jun 2.