基于胆固醇上不同连接方式修饰的穿膜肽脂质体的对比研究  

The comparison between liposomes comprised of cholesterol modified by TAT with different conjugations

作　　者：张莉[1] 唐洁[1] 尹愈佳[1] 覃瑶[1] 刘亚圆[1] 何勤[1] 

机构地区：[1]四川大学华西药学院靶向药物与释药系统教育部重点实验室,四川成都610041

出　　处：《华西药学杂志》2012年第5期490-493,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的对比研究胆固醇上以酯键、醚键的不同连接方式修饰穿膜肽TAT(源于Tat蛋白碱性结构域的短肽)脂质体的体内外特性。方法以Rho-PE为荧光标记物,制备在胆固醇上以酯键、醚键的不同连接方式修饰穿膜肽TAT的脂质体,用激发光散射粒度仪测定其粒径;在小鼠血清中考察两种衍生物材料72 h稳定性;以HUVEC、C6、C26细胞为受试细胞,对标记Rho-PE的两种脂质体进行细胞摄取的定量分析;以DID为荧光标记物,以荷瘤小鼠(C26)为受试动物,考察肿瘤部位定量摄取。结果以酯键、醚键不同连接方式的胆固醇上修饰/未修饰有穿膜肽TAT的脂质体的粒径分别为114.50±12.31、113.80±6.74、103.10±1.91、105.10±2.06 nm;多分散系数(PDI)分别为0.227±0.029、0.207±0.039、0.203±0.009、0.216±0.016;小鼠血清中以醚键连接的胆固醇衍生物材料具有良好的稳定性。胆固醇上以不同连接方式修饰的TAT脂质体中,以醚键连接方式制备的脂质体的体外细胞摄取以及体内肿瘤摄取均优于酯键连接方式制备的脂质体。结论醚键修饰的胆固醇衍生物材料所制备的连接TAT的脂质体相较于酯键连接者,有较好的体内外摄取效果。OBJECTIVE To compare the in vitro and in vivo characteristics of liposomes comprised of cholesterol modified by TAT with different conjugations.METHODS Rho-PE loaded liposomes modified by TAT with ether-linked ester-linked cholesterol were prepared.Particle sizes and Zeta potentials of liposomes were recorded on Malvern Zetasizer Nano ZS90.The stability of two materials was investigated after 72 h incubation in normal mice serum.The uptake of various Rh-PE loaded liposomes by HUVEC,C6,C26 was quantitatively and qualitatively analyzed.DID loaded liposomes modified with or without TAT of different conjuagations were prepared,the uptake of DID in tumor cell was analyzed by flow cytometry.RESULTS The average sizes of ether-linked-TAT LIP,ester-linked TAT LIP and ether-linked LIP and ester-linked LIP were 114.50±12.31,113.80±6.74,103.10±1.91,105.10±2.06 nm,and the PDI were 0.227±0.029,0.207±0.039,0.203±0.009,0.216±0.016,respectively.Ether-linked material was more stable than ester-linked material after 72 h incubation in normal mice serum.Liposomes formulated by cholesterol derivate of ether linkage exhibited a slight higher cell uptake quantitatively and qualitatively.CONCLUSION Liposomes modified by TAT formulated by material with ether linkage shows better cell uptake than material with ester linkage in vitro and in vivo.

关 键 词：胆固醇 TAT 醚键 脂质体 体内外摄取 

分 类 号：R94[医药卫生—药剂学]