反义核酸药物脂质体肝靶向性的研究

目的研究反义核酸药物脂质体给药系统的肝主动靶向性。方法采用薄膜分散法制备脂质体,以花青染料荧光标记脂质体,以荧光分光光度法定量分析;利用肝组织的体内冷冻切片和小鼠体内组织分布研究肝靶向性;检测大鼠肝非实质细胞与肝实质细胞的荧光强度(INPC和IPC)。结果主动靶向脂质体在肝脏中的荧光强度明显强于非主动靶向脂质体,相对摄取率(re)为5.64;非主动靶向脂质体的荧光值比(IPC/INPC)为1.16±0.89,主动靶向脂质体的IPC/INPC为8.24±1.37。结论主动靶向脂质体具有良好的肝实质细胞靶向性和肝靶向性。

Investigation on hepatic targeting of liposomes of antisense oligodeoxynucleotide

Objective To investigate the hepatic targeting of liposomes loading antisense oligodeoxynucleotide.Methods A thin-film dispersing method was used to prepare the liposomes;1,1′-dioctadecyl-3.3,3′,3′tetramethy-lindocarbocyanine perchlorate(DiI) was used as the fluorescent labeling agents to mark the liposomes;the hepatic targeting was confirmed by liver frozen sections and the body distribution;the fluorescence intensity of hepatic parenchymal cells and hepatic nonparenchymal cell were detected.Results Comparing with conventional liposomes,active hepatic targeting liposomes had higher fluorescence intensity of liver frozen sections;liver relative uptake ratio(re)was 5.64;IPC/INPC of conventional liposomes was 1.16±0.89,and IPC/INPC of active targeting liposomes was 8.24±1.37.Conclusions The active hepatic targeting liposomes present highly distribution in liver and hepatic parenchymal cells compared with the conventional liposomes.