[Biodistribution and hepatocytes targeting of cationic liposomes surface-modified with sterylglucoside and golyethylene glycol].
OBJECTIVE
To investigate the biodistribution and the hepatocytes targeting of cationic liposome containing 3beta[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 hepatocytes and non-hepatocytes 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).


CONCLUSIONS
Cationic liposome modified with SG/PEG changed the distribution of asODN. Cationic liposome can target hepatocytes more effective after being modified with SG.
Shi
Jing
J
Department of Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Yan
Wen-Wei
WW
Qi
Xian-Rong
XR
Yang
Li
L
Zhang
Li
L
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002782:Cholestenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D022781:Hepatocytes / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000493:pharmacokinetics; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution
D002782:Cholestenes; D004337:Drug Carriers; D008081:Liposomes; D020319:Oligodeoxyribonucleotides, Antisense; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; C096056:soy derived sterylglucoside mixture; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; D002784:Cholesterol