Wilson Barnabas, Samanta Malay Kumar, Santhi Kumaraswamy, Kumar Kokilampal Perumal Sampath, Paramakrishnan Nallupillai, Suresh Bhojraj
Department of Pharmaceutics, J.S.S. College of Pharmacy, Ootacamund, Tamil Nadu, India.
Eur J Pharm Biopharm. 2008 Sep;70(1):75-84. doi: 10.1016/j.ejpb.2008.03.009. Epub 2008 Mar 27.
The purpose of the present study was to investigate the possibility of targeting an anti-Alzheimer's drug tacrine in the brain using polymeric nanoparticles. Rats obtained 1mg/kg of tacrine by intravenous injection in the form of three preparations: (1) a simple solution in phosphate buffered saline, (2) bound to poly(n-butylcyanoacrylate) nanoparticles, and (3) bound to poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 (Tween 80). After 1h of post injection the rats were killed by decapitation and tacrine concentration in brain, liver, lungs, spleen and kidneys was analyzed by HPLC. A higher concentration of drug tacrine was observed in liver, spleen and lungs with the nanoparticles in comparison to the free drug. The accumulation of drug tacrine in the liver and spleen was reduced, when nanoparticles were coated with 1% polysorbate 80. In the brain a significant increase in tacrine concentration was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the uncoated nanoparticles and the free drug. In conclusion, the present study demonstrates that the brain concentration of intravenously injected tacrine can be enhanced by binding to poly(n-butylcyanoacrylate) nanoparticles, coated with 1% the nonionic surfactant polysorbate 80.
本研究的目的是探讨使用聚合物纳米颗粒将抗阿尔茨海默病药物他克林靶向输送至大脑的可能性。大鼠通过静脉注射三种制剂的形式获得1mg/kg他克林：(1) 磷酸盐缓冲盐水中的简单溶液；(2) 与聚（正丁基氰基丙烯酸酯）纳米颗粒结合；(3) 与涂有1%聚山梨酯80（吐温80）的聚（正丁基氰基丙烯酸酯）纳米颗粒结合。注射后1小时，大鼠断头处死，通过高效液相色谱法分析大脑、肝脏、肺、脾脏和肾脏中的他克林浓度。与游离药物相比，纳米颗粒组大鼠的肝脏、脾脏和肺中观察到更高浓度的他克林。当纳米颗粒涂有1%聚山梨酯80时，他克林在肝脏和脾脏中的蓄积减少。在大脑中，与未涂覆的纳米颗粒和游离药物相比，涂有1%聚山梨酯80的聚（正丁基氰基丙烯酸酯）纳米颗粒组的他克林浓度显著增加。总之，本研究表明，静脉注射的他克林与涂有1%非离子表面活性剂聚山梨酯80的聚（正丁基氰基丙烯酸酯）纳米颗粒结合后，其在大脑中的浓度可以提高。
