Liver Targeting Liposomes Containing β-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 β-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 (DiI) in terms of asialoglycoprotein receptor (ASGP-R)-mediated endocytosis, affinity of Sit-G using IAsys 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.