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-druguptake 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 <100 nm 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. (C) 2016 Elsevier B.V. All rights reserved.