Wilson Barnabas, Samanta Malay Kumar, Santhi Kumaraswamy, Kumar Kokilampal Perumal Sampath, Paramakrishnan Nallupillai, Suresh Bhojraj
Department of Pharmaceutics, J.S.S. College of Pharmacy, Rocklands, Ootacamund, Tamil Nadu-643001, India.
Brain Res. 2008 Mar 20;1200:159-68. doi: 10.1016/j.brainres.2008.01.039. Epub 2008 Jan 26.
Alzheimer's disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavioral disturbances. Alzheimer's disease affects 15 million people worldwide and it has been estimated that Alzheimer's disease affects 4.5 million Americans. Rivastigmine is a reversible cholinesterase inhibitor used for the treatment of Alzheimer's disease. Central nervous system drug efficacy depends upon the ability of a drug to cross the blood-brain barrier and reach therapeutic concentrations in brain following systemic administration. The clinical failures of most of the potentially effective therapeutics to treat the central nervous system disorders are often not due to a lack of drug potency but rather shortcomings in the method by which the drug is delivered. Hence, considering the importance of treating Alzheimer's disease, we made an attempt to target the anti-Alzheimer's drug rivastigmine in the brain by using poly(n-butylcyanoacrylate) nanoparticles. The drug was administered as a free drug, bound to nanoparticles and also bound to nanoparticles coated with polysorbate 80. In the brain a significant increase in rivastigmine uptake was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the free drug. In conclusion that the present study demonstrates that the brain concentration of intravenously injected rivastigmine can be enhanced over 3.82 fold by binding to poly(n-butylcyanoacrylate) nanoparticles coated with 1% nonionic surfactant polysorbate 80.
阿尔茨海默病是一种进行性致命的神经退行性疾病，表现为认知和记忆衰退、日常生活活动能力逐渐受损以及各种神经精神症状和行为障碍。全球有1500万人受阿尔茨海默病影响，据估计，美国有450万人受其影响。卡巴拉汀是一种用于治疗阿尔茨海默病的可逆性胆碱酯酶抑制剂。中枢神经系统药物的疗效取决于药物穿过血脑屏障并在全身给药后在脑内达到治疗浓度的能力。大多数潜在有效的治疗中枢神经系统疾病的疗法在临床上失败，往往不是因为药物效力不足，而是药物递送方法存在缺陷。因此，考虑到治疗阿尔茨海默病的重要性，我们尝试通过使用聚（氰基丙烯酸正丁酯）纳米颗粒将抗阿尔茨海默病药物卡巴拉汀靶向输送至脑内。药物分别以游离药物、与纳米颗粒结合以及与涂有聚山梨酯80的纳米颗粒结合的形式给药。在脑内，与游离药物相比，观察到涂有1%聚山梨酯80的聚（氰基丙烯酸正丁酯）纳米颗粒使卡巴拉汀的摄取量显著增加。总之，本研究表明，静脉注射的卡巴拉汀与涂有1%非离子表面活性剂聚山梨酯80的聚（氰基丙烯酸正丁酯）纳米颗粒结合后，脑内浓度可提高3.82倍以上。
