豆甾醇糖苷/聚乙二醇衍生物修饰的阳性脂质体体内分布和肝实质细胞靶向性  

Biodistribution and hepatoctyes targeting of cationic liposomes surface-modified with sterylglucoside and golyethylene glycol

作　　者：石靖[1] 严文伟[1] 齐宪荣[1] 杨莉[1] 张鹂[1] 

机构地区：[1]北京大学药学院药剂教研室,北京100083

出　　处：《药学学报》2004年第7期551-555,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 ( 3 0 3 712 65 )

摘　　要：目的　研究经豆甾醇糖苷 (sterylglucoside ,SG)修饰的以DC Chol为阳性脂材的脂质体体内分布情况和达到小鼠肝实质细胞靶向的可能性。方法　合成阳性脂材 3β [N (N′ ,N′ 二甲基氨乙基 )氨基甲酰基 ]胆固醇 (DC Chol) ,制备3H 胆固醇标记的阳性脂质体 (caitonicliposome,CL) ,SG和聚乙二醇 二硬酯酰磷酯酰乙醇胺 (PEG DSPE)修饰的阳性脂质体 (SG PEG CL) ,以及包封1 2 5I标记的硫代反义寡核苷酸 (asODN)的阳性脂质体 (SG PEG CL asODN) ,分别测定CL ,SG PEG CL ,SG PEG CL asODN和asODN溶液 (asODN )在小鼠不同器官及CL ,SG PEG CL肝内不同细胞中的分布。结果　CL和SG PEG CL表现较高肝脏聚集性 ,SG PEG CL在肝实质细胞中浓度显著高于CL (P <0 0 1) ,非实质细胞中浓度明显小于CL(P <0 0 1)。SG PEG CL asODN相对于asODN表现出明显的肝脾聚集性 (P <0 0 1)。结论　用阳性脂质体包载基因药物能改善药物的体内分布 。Aim To investigate the biodistribution and the hepatoctyes targeting of cationic liposome containing 3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and surface-modified liposomes with sterylglucoside (SG) and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE). Methods Cationic liposomes (CL) composed of DC-Chol and dipalmitoylphosphatidylcholine (DPPC), SG/PEG modified cationic liposome (SG/PEG-CL), both contained trace 3H-cholesterol ( 3H-Chol) as radiolabel, were prepared. The liposomes encapsulating 125I-labled antisense oligodeoxynucleotide ( 125I-asODN) (SG/PEG-CL-asODN) were also prepared. The biodistribution of CL, SG/PEG-CL, SG/PEG-C2-asODN as well as 125I-asODN solution, were studied. The radioactivities in hepatoctyes and non-hepatoctyes after administration of CL and SG/PEG-CL were determined by infuseing method. Results CL and SG/PEG CL significantly aggregated in liver. The distribution of SG/PEG CL was significantly higher in hepatocytes (P<0.01) and lower in non-hepatocytes (P<0.01) than that of CL. The concentrations of SG/PEG-CL-asODN in liver and spleen were significantly higher than that of asODN solution (P<0.01). Conclusion Cationic liposome modified with SG/PEG changed the distribution of asODN. Cationic liposome can target hepatocytes more effective after being modified with SG.

关 键 词：阳性脂质体 DC—Chol 豆甾醇糖苷 组织分布 肝实质细胞 

分 类 号：R943.4[医药卫生—药剂学] R943.42[医药卫生—药学]