Development and evaluation of brain targeted intranasal alginate nanoparticles for treatment of depression

Development and evaluation of brain targeted intranasal alginate nanoparticles for treatment of depression
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DOI:
10.1016/j.jpsychires.2013.10.011
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发表时间:
2014-01-01
影响因子:
4.8
通讯作者:
Baboota, Sanjula
Baboota, Sanjula
中科院分区:
医学2区
文献类型:
--
作者:
Haque, Shadabul;Md, Shadab;Baboota, Sanjula

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本研究的目的是研究文拉法辛负载的藻酸盐纳米粒(VLF AG-NPs)通过鼻内(i. n.)从鼻子到大脑的传递途径根据各种理化特性制备并优化了VLF AG-NP。采用白化病Wistar大鼠进行强迫游泳实验和自发活动实验,对VLF AG-NP的抗抑郁活性进行体内药效学研究。VLF AG-NP(i.n.)与VLF溶液(i.n.)相比,治疗显著改善了行为分析参数,即游泳、攀爬和不动性。和VLF片剂(口服)。当与VLF溶液(i. n.)和VLF片剂(口服)。在静脉内和鼻内施用罗丹明-123负载的藻酸盐纳米颗粒后,对大鼠的离体器官进行共聚焦激光扫描荧光显微镜研究,以确定其从鼻到脑递送的功效以及其向其他器官的定性分布。通过分别测定VLF AG-NP(i.n.)在血液和脑中的VLF浓度进行脑摄取和药代动力学研究,VLF溶液(i.n.)和VLF溶液(i. v.)。VLF AG-NP(i.n.)与VLF溶液相比(i. n.)和VLF溶液(i.n.)分别在30分钟时的结果表明藻酸盐纳米颗粒对于VLF的直接鼻至脑转运的优越性。因此,VLF AG-NP(i. n.)与VLF溶液相比,VLF AG-NP向大脑递送更大的VLF,这表明VLF AG-NP可能是治疗抑郁症的有希望的方法。(C)2013爱思唯尔有限公司保留所有权利。
The purpose of the present study was to investigate the potential of Venlafaxine loaded alginate nanoparticles (VLF AG-NPs) for treatment of depression via intranasal (i.n.) nose to brain delivery route. The VLF AG-NPs were prepared and optimized on the basis of various physio-chemical characteristics. Pharmacodynamic studies of the VLF AG-NPs for antidepressant activity were carried in-vivo by forced swimming test and locomotor activity test on albino Wistar rats. VLF AG-NPs(i.n.) treatment significantly improved the behavioural analysis parameters i.e. swimming, climbing, and immobility in comparison to the VLF solution(i.n.) and VLF tablet(oral). The intranasal VLF AG-NPs also improved locomotor activity when compared with VLF solution(i.n.) and VLF tablet(oral). Confocal laser scanning fluorescence microscopy studies were performed on isolated organs of rats after intravenous and intranasal administrations of Rodamine-123 loaded alginate nanoparticles to determine its efficacy for nose to brain delivery and also for its qualitative distribution to other organs. Brain uptake and pharmacokinetic studies were performed by determination of VLF concentration in blood and brain respectively for VLF AG-NPs(i.n.), VLF solution(i.n.) and VLF solution(i.v.). The greater brain/blood ratios for VLF AG-NPs(i.n.) in comparison to VLF solution(i.n.) and VLF solution(i.n.) respectively at 30 min are indicative of superiority of alginate nanoparticles for direct nose to brain transport of VLF. Thus, VLF AG-NPs(i.n.) delivered greater VLF to the brain in comparison to VLF solution which indicates that VLF AG-NPs could be a promising approach for the treatment of depression. (C) 2013 Elsevier Ltd. All rights reserved.