Delivery of nanoparticles to the brain detected by fluorescence microscopy

Delivery of nanoparticles to the brain detected by fluorescence microscopy
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DOI:
10.1016/j.ejpb.2008.05.007
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发表时间:
2008-10-01
影响因子:
4.9
通讯作者:
Fricker, Gert
Fricker, Gert
中科院分区:
医学2区
文献类型:
--
作者:
Reimold, Isolde;Domke, Diana;Fricker, Gert

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本研究旨在探索和扩展聚氰基丙烯酸正丁酯(PBCA)纳米粒的应用潜力,以穿过血脑屏障(BBB),并将其内容物输送到中枢神经系统。采用一种新型高效的细乳液法制备了PBCA微球,该方法具有良好的产率和重现性。这些纳米颗粒负载有1.5%(w/v)荧光素-异硫氰酸酯-葡聚糖(FITC-葡聚糖)、1.5%罗丹明-123或7.3%阿霉素。通过动态光散射测定粒径、多分散性指数和zeta电位来表征颗粒。用10% w/v聚山梨酯80包被并给予大鼠。制备脑的冷冻切片,并研究荧光的时间依赖性分布。通过颈动脉注射给予聚山梨酯80-包衣颗粒后,首先在毛细血管腔中检测到荧光,在给药后30 min逐渐转移至毛细血管内皮细胞,在给药后60 min在整个脑组织中相当均匀地分布。在尾静脉给药后60分钟,荧光颗粒可分配给内皮细胞,而在2小时后,观察到在整个脑组织中相当均匀的分布。这些观察结果表明,表面涂覆的PBCA纳米颗粒能够穿过血脑屏障,并作为药物递送系统到达中枢神经系统。(C)2008 Elsevier B. V.保留所有权利。
This study aimed to explore and extend the application potential of poly(n-butylcyano-acrylate) (PBCA) nanoparticles to cross the blood-brain barrier (BBB) and to deliver their content into the central nervous system. PBCA particles were prepared by a new and efficient mini-emulsion method with excellent yield and reproducibility. These nanoparticles were loaded with 1.5% (w/v) fluorescein-isothio-cyanate-dextran (FITC-dextran), 1.5% rhodamine-123 or 7.3% doxorubicin. Particles were characterized by dynamic light scattering determining particle size, polydispersity index and zeta-potential. They were coated with 10% w/v polysorbate 80 and administered to rats. Cryosections of the brain were prepared and time-dependent distribution Of fluorescence was studied. After the administration of polysorbate 80-coated particles by carotic injection, fluorescence could first be detected in capillary lumina with a progressive shift to capillary endothelial cells at 30 min and a rather evenly spread distribution across the brain tissue at 60 min after administration. 60 min after administration into the tail vein, fluorescent particles could be assigned to endothelial cells, whereas after 2 h a rather evenly spread distribution across the brain tissue was seen. These observations indicate that surface-coated PBCA nanoparticles are able to cross the blood-brain barrier and to serve as a drug-delivery, system to the central nervous system. (C) 2008 Elsevier B.V. All rights reserved.