Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles
Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles
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DOI：
10.1023/a:1018983904537
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发表时间：
1999-10-01
影响因子：
3.7
通讯作者：
Kreuter, J
中科院分区：
文献类型：
--
作者：
Gulyaev, AE;Gelperina, SE;Kreuter, J
目的。研究使用胶体载体（纳米颗粒）将抗癌药物输送到大脑的可能性。方法。大鼠通过静脉注射获得 5 mg/kg 的阿霉素。 v. 注射剂有 4 种制剂：盐水中的简单溶液，2.聚山梨酯80 1％盐水中的简单溶液，3.与聚(氰基丙烯酸丁酯)纳米颗粒结合，以及4.与涂有1％聚山梨酯80(Tween80)的聚(氰基丙烯酸丁酯)纳米颗粒结合。 10分钟、1、2、4、6和8小时后处死动物，提取后通过HPLC测定血浆、肝、脾、肺、肾、心脏和脑中阿霉素的浓度。 结果。两种溶液制剂之间没有观察到身体分布的显着差异。这两种纳米颗粒制剂非常显着地降低了心脏浓度。使用聚山梨醇酯 80 包被的纳米颗粒在 2 至 4 小时内实现了高脑阿霉素浓度（>6 μg/g）。其他三种制剂观察到的脑浓度始终低于检测限（<0.1μg/g）。结论。本研究表明，通过与涂有非离子表面活性剂聚山梨酯 80 的可生物降解的聚（氰基丙烯酸丁酯）纳米颗粒结合，全身给药的阿霉素的脑浓度可提高 60 倍以上。包覆颗粒很可能完好无损地到达大脑，并在脑血管内皮细胞胞吞后释放药物。
Purpose. To investigate the possibility of delivering of anticancer drugs into the brain using colloidal carriers (nanoparticles).Methods. Rats obtained 5 mg/kg of doxorubicin by i. v. injection in form of 4 preparations : i. a simple solution in saline, 2. a simple solution in polysorbate 80 1% in saline, 3.bound to poly(butyl cyanoacrylate) nanoparticles, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated with 1% polysorbate 80 (Tween(R) 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liver, spleen, lungs, kidneys, heart and brain were determined after extraction by HPLC.Results. No significant difference in the body distribution was observed between the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentrations of doxorubicin (>6 mu g/g) were achieved with the nanoparticles overcoated with polysorbate 80 between 2 and 4 hours. The brain concentrations observed with the other three preparations were always below the detection Limit (< 0.1 mu g/g).Conclusions. The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80. It is highly probable that coated particles reached the brain intact and released the drug after endocytosis by the brain blood vessel endothelial cells.