纳米载药胶束对乙酰胆碱酯酶抑制作用的研究  

Inhibitory Effect of Drug-Loaded Nano-Micelles on Acetylcholinesterase

作　　者：段丽红 王春宝 李映红[1,3] 吴正治[1,3] 李利民 张晓丽[3] DUAN Li-hong;WANG Chun-bao;LI Ying-hong;WU Zheng-zhi;LI Li-min;ZHANG Xiao-li(Shenzhen Institute of Geriatrics, Guangdong Shenzhen 518035;Harvard Medical School, Spalding rehabilitation hospital, USA Boston 02129;the First Affiliated Hospital of Shenzhen University, Guangdong Shenzhen 518035;Guangxi University of Science and Technology, Guangxi Liuzhou 545006;South China University of Technology,Guangdong Guangzhou 510641)

机构地区：[1]深圳市老年医学研究所,广东深圳518035 [2]哈佛医学院斯波尔丁康复医院,波士顿美国02129 [3]深圳大学第一附属医院,广东深圳518035 [4]广西科技大学,广西柳州545006 [5]华南理工大学,广东广州510641

出　　处：《深圳中西医结合杂志》2019年第7期1-5,199,共6页Shenzhen Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家留学基金委留学资助项目(201708440006);国家自然科学基金资助项目(81574038;81473742);广东省自然科学基金资助项目(2017A030313842);广东省科技计划资金项目资助项目(2017A050506007);深圳市科技研发资金基础研究项目资助项目(JCYJ20170412161254416);深圳市医疗卫生三名工程资助项目(SZSM20162049)

摘　　要：目的:阿尔茨海默病(AD)是一个重大的社会和医学难题。石蒜生物碱作为乙酰胆碱酯酶(AChE)抑制剂,具有治疗AD的潜力,但其体内分布广泛,毒副作用较大。为了解决这一问题,应增强石蒜生物碱的大脑靶向性,提高其生物利用度并降低毒副作用,本研究成功地以血脑屏障内皮细胞的低密度脂蛋白受体作为治疗AD的靶点,采用温和条件下的点击化学,实现了对石蒜生物碱的负载,将纳米药物载体高选择性地、定量铆钉在靶向低密度脂蛋白表面,形成纳米载药胶束。方法:运用TLC生物自显影法和Ellman法对两种纳米载药胶束抑制AChE的活性进行研究。结果:加兰他敏胶束和力可拉敏胶束可显著抑制AChE活性,并呈现显著的量效关系,加兰他敏胶束溶液和力可拉敏胶束溶液的抑制率分别最高达到了93.0%和85.0%;而相同含药浓度时,加兰他敏胶束溶液的抑制率稍高于力可拉敏胶束溶液的抑制率。结论:两种胶束都可显著抑制AChE活性,其中加兰他敏胶束效果更佳。Objective Alzheimer's disease is a major social and medical problem. Alkaloid has the potential to treat Alzheimer's disease as the inhibitor of acetylcholinesterase, but its wide distribution and side effects limit its application. In order to solve this problem, enhance the brain target, improve its bioavailability and reduce the side effects, the alkaloids is considered as the research object, the low density lipoprotein receptor of blood-brain barrier endothelial cells as a target for the treatment of Alzheimer's disease. The alkaloids is loaded through a new method by using click chemistry under mild conditions. Nano micelles were prepared by high selectiviely and quantitatively loaded drug carrier on targeted low density lipoprtein surface. Methods The inhibition activities of acetylcholinesterase of two kind nano micelles were studied by TLC and Ellman methods. Results Two of kind nano micelles can inhibit the activity of AChE. The inhibition rates of two kinds nano micelles were increased with the drug concentration increased. The highest inhibition rate of galanthamine micelle and lycoramine micelle reached 93% and 85% respectively. Inhibition rate of galanthamine micelle was higher thah lycoramine micelle. Conclusion Both micelles can significantly inhibit AChE activity, and galantamine micelles are more effective.

关 键 词：石蒜生物碱 乙酰胆碱酯酶抑制剂 纳米胶束 阿尔茨海默病 

分 类 号：R943[医药卫生—药剂学]