Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study
Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study
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DOI：
10.3109/02652049809006836
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发表时间：
1998-01-01
影响因子：
3.9
通讯作者：
Kreuter, J
中科院分区：
文献类型：
--
作者：
Alyautdin, RN;Tezikov, EB;Kreuter, J
已经研究了使用聚山梨酯80涂覆的聚氰基丙烯酸正丁酯纳米颗粒将低分子极性亲水性药物递送至CNS的可能性。筒箭毒碱（一种季铵盐）不能穿透正常完整的血脑屏障。然而，将这种药物直接注射到大脑的脑室中会引起癫痫样发作的发展，如脑电图（EEG）所评估的。一个在原位灌注大鼠脑技术被用作一个实验技术，同时记录的EEG。在酸性介质中通过氰基丙烯酸正丁酯聚合制备纳米粒子。在将负载筒箭毒碱的聚山梨醇酯80包覆的纳米颗粒引入到灌注液中后15分钟，EEG中出现癫痫样尖峰。脑室注射筒箭毒碱引起的EEG癫痫发作后5分钟的外观。筒箭毒碱溶液和不含聚山梨酯80或聚山梨酯80和筒箭毒碱的混合物的筒箭毒碱负载纳米颗粒都不能影响EEG。因此，只有将筒箭毒碱装载到聚山梨酯80包被的纳米颗粒上似乎能够使该季铵化合物转运通过血脑屏障。
The possibility of using polysorbate 80-coated polybutylcyanoacrylate nanoparticles to deliver low molecular polar hydrophilic drugs to the CNS has been studied. Tubocurarine (a quaternary ammonium salt) does not penetrate the normal intact blood-brain barrier. However, the injection of this drug directly into the cerebral ventricles of the brain provokes the development of epileptiform seizures as assessed by electroencephalogram (EEG). An in situ perfused rat brain technique was used as an experimental technique together with a simultaneous recording of the EEG. Nanoparticles were prepared by butylcyanoacrylate polymerization in an acidic medium. Fifteen minutes after the introduction of tubocurarine-loaded polysorbate 80-coated nanoparticles into the perfusate, epileptiform spikes in the EEG appeared. Intraventricular injection of tubocurarine caused the appearance of the EEG seizures 5 min after administration. Neither tubocurarine solution nor tubocurarine-loaded nanoparticles without polysorbate 80 or a mixture of polysorbate 80 and tubocurarine were able to influence the EEG. Thus only the loading of tubocurarine onto the polysorbate 80-coated nanoparticles appears to enable the transport of this quaternary ammonium compound through the blood-brain barrier.