The Permeability of Puerarin Loaded Poly(butylcyanoacrylate) Nanoparticles Coated with Polysorbate 80 on the Blood-Brain Barrier and Its Protective Effect against Cerebral Ischemia/Reperfusion Injury
The Permeability of Puerarin Loaded Poly(butylcyanoacrylate) Nanoparticles Coated with Polysorbate 80 on the Blood-Brain Barrier and Its Protective Effect against Cerebral Ischemia/Reperfusion Injury
复制标题
聚山梨酯80包覆葛根素聚氰基丙烯酸丁酯纳米粒子对血脑屏障的通透性及其对脑缺血/再灌注损伤的保护作用
DOI：
10.1248/bpb.b12-00769
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发表时间：
2013-08-01
影响因子：
2
通讯作者：
Zhang, Qing-zhu
中科院分区：
文献类型：
--
作者：
Zhao, Li-xia;Liu, An-chang;Zhang, Qing-zhu
葛根素(PUE)是治疗中风的良好候选药物，但其在脑内的低浓度限制了其疗效。本研究的目的是设计和表征聚山梨酯80(PS 80)包覆的聚氰基丙烯酸丁酯纳米粒(PBCN)，评价其对PUE透过血脑屏障(BBB)的影响以及其对脑缺血再灌注损伤的影响。采用阴离子聚合法制备了PUE负载型PBCN，平均粒径为201.2 am，Zeta电位为-7.72 mV。PUE在纳米粒中的体外释放行为呈现先爆发后持续释放的两相分布方式。静脉给药后的药代动力学和脑内生物分布结果表明，PUE-PBCN的血药浓度和脑内药物浓度均高于游离药物。此外，与游离药物相比，静脉注射PUE负载的PBCN对大鼠局灶性脑缺血损伤具有更好的神经保护作用，可显著降低神经功能评分，增加体重，降低脑含水量，缩小脑梗塞体积。结果表明，该制剂可以减少卒中治疗所需的总剂量，同时减少与剂量相关的毒性。提示PBCN可促进PUE向脑内转运，有可能成为局部脑缺血损伤的神经保护剂。
Puerarin (PUE) is a good candidate for treating stroke, but its low concentration in brain after administration limits its curative efficacy. The aim of the present work was to design and characterize PUE loaded poly(butylcyanoacrylate) nanoparticles (PBCN) coated with polysorbate 80 (Ps 80), and to evaluate the effect of PBCN on the permeability of PUE across the blood brain barrier (BBB) and the effect of PUE loaded PBCN on the cerebral ischemia/reperfusion injury. PUE loaded PBCN were successfully prepared by anionic polymerization method with the mean particle size of 201.2 am and the zeta potential of -7.72 mV. The in vitro release behavior of PUE from the nanoparticles showed a biphasic profile manner with an initial burst release followed by a sustained release. The results of pharmacokinetic and biodistribution to brain performed in mice after intravenous administration showed that the drug concentrations in blood and brain for PUE loaded PBCN were both greater than these for the free drug. Moreover, compared with free drug, the vein injection of PUE loaded PBCN exerted the better neuroprotective effect in rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, lowing brain water content, and reducing the infarct volume. The results indicated that this preparation may reduce the total dose required for the stroke therapy with concurrent reduction in dose related toxicity. All these findings suggest that PBCN could enhance the transport of PUE to brain and have a potential as a neuroprotective agent in the focal cerebral ischemic injury.