title: Characteristics and biodistribution of soybean sterylglucoside and polyethylene glycol-modified cationic liposomes and their complexes with antisense oligodeoxynucleotide.
abstract: A novel cationic liposome modified with soybean sterylglucoside (SG) and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) as a carrier of antisense oligodeoxynucleotide (ODN) for hepatitis B virus (HBV) therapy was constructed. Characteristics of the cationic liposomes modified with SG and PEG (SG/PEG-CL) and their complexes with 15-mer phosphorothioate ODN (SG/PEG-CL-ODN complex) were investigated by incorporation efficiency, morphology, electrophoresis, zeta potentials, and size analysis. Antisense activity of the liposomes and ODN complexes was determined as hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in HepG2 2.2.15 cells by ELISA. Their tissue and intrahepatic distribution were evaluated following intravenous injection in mice. The complexes gained high incorporation efficiency and intact vesicular structure with mean size at approximately 200 nm. The SG/PEG-CL-ODN complexes enhanced the inhibition of both HBsAg and HBeAg expression in the cultured HepG2 2.2.15 cells relative to free ODN. The uptake of SG/PEG-CL and nonmodified cationic liposomes (CL) was primarily by liver, spleen, and lung. Furthermore, the concentration of SG/PEG-CL was significant higher than that of CL in hepatocytes at 0.5 hr postinjection. The biodistribution of SG/DSPE-CL-ODN complex compare with free ODN showed that liposomes enhanced the accumulation of ODN in the liver and spleen, while decreasing its blood concentration. SG/PEG-CL-mediated ODN transfer to the liver is an effective gene delivery method for cell-specific targeting, which has a potential for gene therapy of HBV infections. SG and PEG-modified cationic liposomes have proven to be an alternative carrier for hepatocyte-selective drug targeting.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Yan
authors.forename: Xian-Rong
authors.initials: XR
authors.lastname: Qi
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
authors.forename: Tsuneji
authors.initials: T
authors.lastname: Nagai
mesh_terms: D000818:Animals; D002412:Cations; D002782:Cholestenes / Q000737:chemistry / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D018390:Gene Targeting; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008081:Liposomes / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D013025:Glycine max / Q000737:chemistry; D014018:Tissue Distribution; D014162:Transfection; D014316:Tritium; D014407:Tumor Cells, Cultured
chemical_list: D002412:Cations; D002782:Cholestenes; D007457:Iodine Radioisotopes; D008081:Liposomes; D020319:Oligodeoxyribonucleotides, Antisense; C096056:soy derived sterylglucoside mixture; D014316:Tritium; D011092:Polyethylene Glycols