自组装白蛋白纳米粒作为阿克拉霉素A递送载体  

Self-assembled albumin nanoparticles as a nanocarrier for aclacinomycin A

作　　者：陈美惠[1] 丁厚伟 张庆明[1] 龚光明[1] 朱庆 王曙东[1] CHEN Mei-hui;DING Hou-wei;ZHANG Qing-ming;GONG Guang-ming;ZHU Qing;WANG Shu-dong(Department of Pharmaceutical Preparation,Nanjing General Hospital of Nanjing Military Region,PLA,Nanjing 210002,Jiangsu,China;College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,Jiangsu,China)

机构地区：[1]南京军区南京总医院制剂科,南京210002 [2]南京中医药大学药学院,南京210023

出　　处：《东南国防医药》2017年第6期565-569,共5页Military Medical Journal of Southeast China

基　　金：国家自然科学基金(31671026)

摘　　要：目的本研究旨在通过阿克拉霉素(ACM)共价结合氨基氧乙酸(AOA)产生的活性中间体,以降低ACM毒性和提高靶向药物。方法采用三(2-羧乙基)膦(TCEP)作为二硫键断裂分子,通过分子间的"打开-中间-闭合"开关制备人血清白蛋白(HSA)的自组装纳米粒(Nanoparticle,NPs)。结果核磁共振氢谱(~1H-NMR)分析表明ACM和AOA之间的结合发生在ACM的酮基(^(12)C)位置。HSA纳米粒(NPs-ACM)负载ACM的载药量为7.4%。NPs-ACM的释放与pH相关。与游离ACM相比,NPs-ACM的细胞毒性和心脏毒性降低。体内研究表明,NPs-ACM对荷瘤小鼠靶向性比游离ACM高4倍(P<0.05)。结论纳米粒NPs-ACM前体药物是理想的ACM肿瘤靶向药物载体。ObjectiveThis study aimed to reduce the cytotoxicity and improve the targeting of aclacinomycin(ACM)by covalently coupling it with amino-oxyacetic acid(AOA)to generate an active intermediate,AOA-ACM.MethodsAOA-ACM was conjugated with self-assembled human serum albumin(HSA)nanoparticles constructed using Tris(2-carboxyethy1)phosphine(TCEP)as disulfide bond breaking molecules.ResultsConjugation between ACM and albumin nanoparticles was found to occur at an ACM ketone site using1H-NMR.The drug loading efficiency of ACM conjugated with HSA nanoparticles(NPs-ACM)was74%(molar ratio=6:1).The release of NPs-ACM was pH dependent.The cytotoxicity and cardiotoxicity of NPs-ACM were reduced compared with the free ACM.Vivo studies indicated that NPs-ACM exhibited fourfold higher tumor targeting capability on S180-tumor-bearing mice compared with the free ACM(P<0.05).ConclusionThe NPs-ACM prodrug is ideal tumor targeting drug carriers for ACM.

关 键 词：白蛋白 阿克拉霉素A 药物递送 

分 类 号：R945[医药卫生—微生物与生化药学]