In this study, three types of galactosylated cholesterol (i.e., gal-PEG194-chol, gal-PEG1000-chol and gal-PEG2000-chol) were synthesized with one terminal of polyethylene glycol of various chain lengths conjugated to the galactoside moiety, and the other terminal conjugated to the cholesterol. The galactose-modified liposomes were prepared by thin film-hydration method and doxorubicin (DOX) was loaded to the liposomes by using a ammonium sulfate gradient procedure. The liposomal formulations with galactosylated cholesterol were characterized. Flow cytometry and laser confocal scanning microscopy analyses showed that the galactose-modified liposomes facilitated the intracellular uptake of liposomes into HepG2 via asialoglycoprotein receptor (ASGP-R) mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of galactose-modified liposomes was higher than that of the unmodified liposomes. Additionally, the study on frozen section of liver showed that the galactose-modified liposomes enhanced the intracellular uptake of liposomes into hepatocytes. Taken together, these results suggested that liposomes containing such galactosylated cholesterol (i.e., gal-PEG-chol), had a great potential as drug delivery carriers for hepatocyte-selective targeting.
在这项研究中,合成了三种类型的半
乳糖化
胆固醇(即gal-P
EG194-chol、gal-P
EG1000-chol和gal-P
EG2000-chol),它们的一个端基通过不同链长的聚
乙二醇与半
乳糖基团连接,另一个端基与
胆固醇连接。通过薄膜
水化法制备了半
乳糖修饰的脂质体,并利用
硫酸铵梯度法将
阿霉素(DOX)装载到脂质体中。对含有半
乳糖化
胆固醇的脂质体进行了表征。流式细胞术和激光共聚焦扫描显微镜分析显示,半
乳糖修饰的脂质体通过脱
唾液酸糖蛋白受体(ASGP-R)介导的内吞作用促进了脂质体进入HepG2细胞的细胞内摄取。细胞毒性测定表明,半
乳糖修饰脂质体的细胞增殖抑制效果高于未修饰脂质体。此外,对肝脏冷冻切片的研究表明,半
乳糖修饰的脂质体增强了脂质体进入肝细胞的细胞内摄取。综上所述,这些结果表明,含有这种半
乳糖化
胆固醇(即gal-P
EG-chol)的脂质体,作为肝细胞选择性靶向药物传递载体具有巨大的潜力。