基于可降解两性离子聚碳酸酯纳米胶束的设计合成及其血液长循环研究  

Study on long blood⁃circulation of nano⁃micelles based on biodegradable zwitterionic polycarbonate

作　　者：张平 徐云燕 陈莹 王可 陈维 张庆明 ZHANG Ping;XU Yunyan;CHEN Ying;WANG Ke;CHEN Wei;ZHANG Qingming(Department of Pharmacy,General Hospital of Eastern Theater Command of PLA,Nanjing 210002;College of Engineering,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]东部战区总医院药剂科,江苏南京210002 [2]中国药科大学工学院,江苏南京210009

出　　处：《南京医科大学学报（自然科学版）》2024年第3期329-335,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(52173294)。

摘　　要：目的:为了克服传统纳米药物稳定性差、血液循环时间短和免疫原性等问题,设计制备了拥有良好稳定性和非特异蛋白质抗性的两性离子纳米药物载体。方法:通过开环聚合和Michael加成后聚合修饰设计并合成一种可生物降解的羧酸甜菜碱型两性离子功能化聚碳酸酯共聚物PAC(TCB),采用溶剂交换法制备得到尺寸为160 nm的胶束。结果:细胞摄取和毒性实验结果表明,PAC(TCB)胶束具有肿瘤细胞摄取效率高、生物相容性好的优点;溶血和体内血液循环实验结果显示,PAC(TCB)胶束具有低免疫原性和长循环特性,且多次注射后不会产生抗体。结论:可生物降解的两性离子功能化聚碳酸酯作为纳米载体在体内药物递送领域具有巨大潜力。Objective:To overcome the drawbacks of traditional nanomedicines with a poor stability,a short blood circulation,and a high immunogenicity,a novel zwitterionic nano⁃vector with sterling stability and non⁃specific protein resistance were designed and prepared.Methods:A biodegradable carboxybetaine(CB)⁃modified polycarbonate[PAC(TCB)]was designed and synthesized by ring⁃opening polymerization and Michael addition reaction,which can form the micelles of around 160 nm via a solvent displacement method.Results:Cellular uptake and cytotoxicity experiments demonstrated that PAC(TCB)micelles possessed the superior characteristics of an efficient cell internalization,and an excellent biocompatibility.The hemolysis assay and in vivo pharmacokinetic experiments confirmed that PAC(TCB)micelles led to a low immunogenicity,a prolonged blood circulation and a negligible antibody effect after repeated injections.Conclusion:The biodegradable zwitterionic⁃functionalized polycarbonate displays a colossal potential as the nano⁃vector in drug delivery.

关 键 词：两性离子聚碳酸酯 低免疫原性 抗蛋白吸附 长循环 药物递送 

分 类 号：R967[医药卫生—药理学]