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;唐洁;尹愈佳;覃瑶;刘亚圆;何勤;
Author：
收稿日期： 年卷（期）页码：2012,27(05):-490-493
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：胆固醇;TAT;醚键;脂质体;体内外摄取
Key words：
基金项目：
中文摘要
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。
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