聚乙二醇-脂质衍生物修饰对脂质体稳定性的影响  

Effect of polyethylene glycol-lipid derivatives on the stability of grafted liposomes

作　　者：徐洋[1] 石莉[2] 邓意辉[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]辽宁省药物研究院,辽宁沈阳110015

出　　处：《药学学报》2011年第10期1178-1186,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81072602)

摘　　要：聚乙二醇-脂质(polyethylene glycol-lipid,PEG-lipid)衍生物具有增加脂质体的稳定性、延长其血液循环半衰期、提高其肿瘤靶向效率及增强药物疗效等优势。深入研究不同PEG-lipid衍生物修饰对脂质体的物理、化学和生物学稳定性的影响,有利于解决目前PEG化脂质体存在的问题,如静脉重复注射时引起的加速血液消除(accelerated blood clearance,ABC)现象,为开发新型靶向制剂奠定基础。本文主要综述了PEG与脂质之间的连接键如酰胺键、醚键、酯键和二硫键,脂质种类如常用的磷脂酰乙醇胺、胆固醇和二酰甘油,脂质的性质即脂肪链长度与饱和度,PEG的端基如甲氧基、羧基、氨基,PEG的相对分子质量和PEG-lipid的摩尔比对PEG化脂质体在体内外稳定性的影响。It is reported that polyethylene glycol-lipid（PEG-lipid） derivatives increase liposomes stability,prolong the blood circulation of liposomes,enhance their tumor-targeting efficiency,and improve drug efficacy.Therefore,it is of great importance to investigate the influence of modified PEG-lipid derivatives on the physical,chemical,and biological characteristics of liposomes for the promotion of dealing with the existed problems,such as the accelerated blood clearance（ABC） phenomenon when repeated intravous injection at a certain time-interval,and developing novel targeted pharmaceutical preparations.In this review,the effects of modified PEG-lipid derivatives were summarized in many aspects.It indicats that the chemical bonds（amide,ether,ester,and disulfide） between PEG and lipid,as well as the species of lipids,such as the commonly used phosphatidylethanolamine,cholesterol,and diacylglycerol have substantial effects on the grafted liposomes stability in vitro and in vivo.Besides,the properties of lipids（the fatty acid chain length and saturation） and the groups（methoxy,carboxylic and amino） at the distal ends of the PEG chains were also considered to be important factors.In the end,the influence of the average molecular weight of PEG and the molar ratio of PEG-lipid derivatives in the total lipid were further focused.

关 键 词：聚乙二醇-脂质衍生物 脂质体 稳定性 

分 类 号：R943[医药卫生—药剂学]