Uptake of liposomes surface-modified with glycyrrhizin by primary cultured rat hepatocytes.
Previously, we synthesized 30-stearyl glycyrrhizin (GLOSt) and reported that small unilamellar liposomes containing GLOSt (GLOSt-SUV) accumulated in the liver several times more than the control liposomes (control-SUV). In the present study, to determine the interaction between GLOSt-SUV and hepatocytes, in vitro uptake experiments were achieved with primary cultured rat hepatocytes. The uptake amount of GLOSt-SUV by rat hepatocytes was considerably higher compared to the control-SUV, while GLOSt-SUV showed about a 10-fold higher uptake level than the control-SUV during 2 h of incubation. It was assumed that GLOSt-SUV not only bind to the surface of the hepatocytes but are internalized and degraded in the cells, because at 37 degrees C, GLOSt-SUV were taken up and the level of the degradable marker was lower than the inert marker, and this did not occur at 4 degrees C. Since the uptake of GLOSt-SUV was inhibited by glycyrrhizin (GL), it was suggested that a binding-site for GL is present on the surface of hepatocytes, and GLOSt-SUV are likely to be internalized via this site by the hepatocytes. Furthermore, it was confirmed that the efficacy of GLOSt on liposomes is not affected by the fluidity of the liposomal membrane.
Osaka
S
S
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Tsuji
H
H
Kiwada
H
H
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D008081:Liposomes / Q000493:pharmacokinetics*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008560:Membrane Fluidity; D051381:Rats; D017208:Rats, Wistar
D004337:Drug Carriers; D008081:Liposomes; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid