大豆糖苷修饰阳离子脂质体的体外肝细胞靶向性

Liver targeting of cationic liposomes modified with soybean-derived sterylglucoside in vitro

目的研究肝靶向物质大豆糖苷(soybean-derived sterylglucoside,SG)的加入对阳离子脂质体肝细胞靶向性的影响。方法以荧光素钠(FS)为模型药物,采用HepG22.2.15细胞模型和SD雄性大鼠,检测SG,SG/Brij-35(卞泽-35)和SG/PEG-DSPE(polyethyleneglycol-distearoylphos phatidylethanolamine)修饰的阳离子脂质体的物理化学性质,在细胞培养水平和离体肝脏水平考察阳离子脂质体的转染和肝细胞选择性。结果未修饰以及SG,SG/Brij-35和SG/PEG-DSPE修饰的FS阳离子脂质体在中性溶液中的包封率分别为91·74%,88·46%,89·70%和83·12%,粒径分别为124·4,113·7,110·8和93·0nm,空白脂质体在溶液中表面电荷为正。细胞培养和肝脏灌流结果说明,阳离子脂质体的转染率显著高于中性脂质体,SG单独修饰后的阳离子脂质体的细胞转染率较未修饰有显著提高,SG/Brij-35修饰的阳离子脂质体则表现出肝实质细胞选择性。结论阳离子脂质体可以促进FS进入肝脏细胞,具有较高的肝细胞摄取率,而SG/Brij-35的修饰可以提高脂质体的肝细胞选择性。

Aim To construct a liposomal liver targeting delivery system by adding soybean-derived sterylglucoside （SG） to the cationic liposomes. Methods The physico-chemical properties of SG modified cationic lipsomes were investigated using fluorescein sodium （FS） as a model drug, as well as the interaction of SG modified liposomes with HepG2 2. 2. 15 cells in the point of involvement of asialoglycoprotein receptor （ASGP-R） mediated transfection. Liver targeting of modified cationic liposomes were also investigated using liver perfusing technique, and hepatoctyes and non-hepatoctyes were separated and examined after perfusing. Results All the formula yielded high incorporation efficiency （83.12% - 91.74% ） , small particle size （93.0 -124. 4 nm）. The （potential of blank liposomes all showed positive values. The transfection efficiency of FS entrapped in SG-liposomes with HepG2 2.2.15 was significantly higher than that of liposomes without modification. The transfection of SG-liposomes were reduced significantly by the 20/30 mmol galactose as a competitor of ASGP-R. All the cationic liposomes showed high level of liver uptake of FS. Compared with the uptake of non-hepatoctyes of each respectively, only SG/Brij-35 liposomes showed difference in FS uptake by hepatoctyes （P 〈 0. 05 ）. Conclusion It showed that SG/Brij-35 modified cationic liposomes are potentially useful drug carrier to liver but may be affected by different modification.