Ahmad Niyaz, Ahmad Rizwan, Naqvi Atta Abbas, Alam Md Aftab, Ashafaq Mohammad, Samim Mohd, Iqbal Zeenat, Ahmad Farhan Jalees
Department of Pharmaceutics, College of Clinical Pharmacy, Dammam University, Dammam 31441, Saudi Arabia.
Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Dammam University, Dammam 31441, Saudi Arabia.
Int J Biol Macromol. 2016 Oct;91:640-55. doi: 10.1016/j.ijbiomac.2016.06.001. Epub 2016 Jun 2.
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.
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.).
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.
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.
芦丁是一种有效的抗氧化剂，据报道可降低缺血性疾病的风险。我们的研究旨在通过离子凝胶法制备芦丁包封的壳聚糖纳米颗粒（RUT-CS-NPs），并基于不同参数，即表面形态表征、体外或体内释放、动态光散射和差示扫描量热法（DSC），来确定其治疗脑缺血的效果。
采用超高效液相色谱-电喷雾电离-四极杆-飞行时间串联质谱（UPLC-ESI-Q-TOF-MS/MS）评估优化后的RT-CS-NPs1对脑内药物摄取的情况，并跟踪其鼻内给药后的药代动力学、生物分布、脑靶向效率和潜力。
该制剂的粒径<100nm，受药物与壳聚糖比例的显著影响，芦丁的包封率和载药量分别为84.98%±4.18%和39.48%±3.16%。与静脉给药相比，药代动力学、生物分布、脑靶向效率（1443.48±39.39%）和脑药物靶向潜力（93.00±5.69%）显示芦丁在脑内的生物利用度有所提高。此外，在鼻内给予RUT-CS-NPs后，在大脑中动脉闭塞（MCAO）诱导的脑缺血大鼠模型中观察到神经行为活性改善、组织病理学变化以及梗死体积减小的效果。
如在该制剂的高靶向潜力和效率后所观察到的，粘膜粘附性RT-CS-NPs1具有重要作用；RUT-CS-NPs能更有效地进入并轻松靶向大脑。
