title: Liver targeting liposomes containing beta-sitosterol glucoside with regard to penetration-enhancing effect on HepG2 cells.
abstract: The aim of this study was to examine the interaction of soybean-derived sterylglucoside (SG) with the human hepatoblastoma cell line HepG2 with regard to the penetration-enhancing effect of beta-sitosterol glucoside (Sit-G) to clarify the accumulation of SG-containing liposomes (SG-liposomes) to the liver in vivo. The approach was based on measurement of the association of SG-liposomes labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) in terms of asialoglycoprotein receptor (ASGP-R)-mediated endocytosis, affinity of Sit-G using lAsys and the association of FITC-dextran 4400 (FD-4) increased by Sit-G with the cells. The association of SG-liposomes was decreased by addition of asialofetuin, suggesting that SG-liposomes might be taken up via ASGP-R. Sit-G showed higher affinity with HepG2 cells than HeLa cells, and enhanced the association of FD-4 depending on the incubation time and Sit-G concentrations. Significant positive correlations were found between Sit-G and FD-4 association with the cells, indicating that Sit-G enhanced the drug penetration by distribution in cell membranes. The high degree of liver association of SG-liposomes in vivo might be related to recognition of glucose residues of SG by ASGP-R and to the high affinity and penetration-enhancing effect of Sit-G with hepatocytes.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.forename: Kouji
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Tsuneji
authors.initials: T
authors.lastname: Nagai
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D037263:Asialoglycoprotein Receptor / Q000378:metabolism; D001212:Asialoglycoproteins / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D005079:Excipients / Q000378:metabolism; D060748:Fetuins; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D012855:Sitosterols / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D005079:Excipients; D060748:Fetuins; D008081:Liposomes; D012855:Sitosterols; D000509:alpha-Fetoproteins; C017029:asialofetuin; D016650:Fluorescein-5-isothiocyanate; C011015:lyoniside