a Department of Pharmaceutics, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University (Formerly University of Dammam) , Dammam , Kingdom of Saudi Arabia.
b Department of Pharmaceutical Chemistry, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University (Formerly University of Dammam) , Dammam , Kingdom of Saudi Arabia.
Artif Cells Nanomed Biotechnol. 2018 Jun;46(4):717-729. doi: 10.1080/21691401.2017.1337024. Epub 2017 Jun 12.
Quercetin (QUR), as an antioxidant flavonoid, exhibits potential role in the amelioration of cerebral ischaemia; however, poor solubility as well as oral absorption results low serum and tissue levels for this drug.
To enhance bioavailability, this study aims to prepare QUR nanoemulsions and administer via non-invasive nasal route in order to evaluate the drug targeting in brain.
Quercetin mucoadhesive nanoemulsion (QMNE) was prepared (ionic gelation method) and optimized using various parameters, that is, particle size, entrapment efficiency, zeta potential and ex vivo permeation study.
The results observed for optimized QMNE were as follows: mean globule size (91.63 ± 4.36 nm), zeta potential (-17.26 ± 1.04 mV), drug content (99.84 ± 0.34%) and viscosity (121 ± 13 cp). To evaluate the extent of bioavailability for QMNE via post-intranasal (i.n.) administration, Ultra performance liquid chromatography-mass spectroscopy (UPLC-ESI-Q-TOF-MS/MS)-based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (9333.33 ± 39.39%) and brain drug-targeting potential (2181.83 ± 5.69%) which revealed enhanced QUR brain bioavailability as compared to intravenous administration (i.v.). Furthermore, improved neurobehavioral activity (locomotor and grip strength), histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic rats model after i.n. administration of QMNE.
This study supports a significant role for QMNE in terms of high brain-targeting potential and formulation efficiency due to ease of access and effective targeting in brain.
槲皮素（QUR）作为一种抗氧化黄酮类化合物，在改善脑缺血方面具有潜在作用；然而，由于其溶解度差和口服吸收不良，导致该药物在血清和组织中的水平较低。
为了提高生物利用度，本研究旨在制备 QUR 纳米乳剂并通过非侵入性鼻内途径给药，以评估药物在大脑中的靶向作用。
采用离子凝胶法制备并优化了槲皮素黏膜黏附纳米乳剂（QMNE），考察了各种参数，即粒径、包封率、Zeta 电位和体外渗透研究。
优化后的 QMNE 的结果如下：平均粒径（91.63±4.36nm）、Zeta 电位（-17.26±1.04mV）、药物含量（99.84±0.34%）和黏度（121±13cp）。为了评估经鼻内（i.n.）给药后 QMNE 的生物利用度程度，建立并验证了基于超高效液相色谱-电喷雾串联四极杆飞行时间质谱（UPLC-ESI-Q-TOF-MS/MS）的药代动力学、生物分布、脑靶向效率（9333.33±39.39%）和脑药物靶向潜力（2181.83±5.69%），与静脉给药（i.v.）相比，这表明 QUR 的脑生物利用度得到了提高。此外，经 i.n.给予 QMNE 后，在大脑中动脉闭塞（MCAO）诱导的脑缺血大鼠模型中观察到改善的神经行为活动（运动和握力）、组织病理学和减少梗死体积的效果。
本研究支持 QMNE 在高脑靶向潜力和制剂效率方面具有重要作用，因为它易于进入和有效靶向大脑。
