Targeting of Liposomes Surface-Modified with Glycyrrhizin to the Liver. I. Preparation and Biological Disposition

Abstract

We consider glycyrrhizin to be a new ligand for liposomes to the liver because it is known that about 80% of glycyrrhizin is excreted into the bile after intravenous administration in rats. In order to modify the liposomal surface with glycyrrhizin, 30-stearyl glycyrrhizin (GLOSt), one of the lipophilic glycyrrhizin derivatives, was synthesized. The structure of this new compound was identified by nuclear magnetic resonance (NMR), infrared (IR) and mass spectra (MS). Sonicated liposomes were prepared from hydrogenated egg phosphatidylcholine-cholesterol-GLOSt or dicetyl phosphate (DCP) (4:4:1) and were labelled with [3H]inulin as an aqueous marker. It was confirmed by measuring the encapsulation efficiencies and the mean diameters that GLOSt-containing sonicated liposomes (GLOSt-SUV) were SUV-type as well as DCP-containing control liposomes (control-SUV). Four hours after intravenous injection into rats at a dose of 90 μmol as total lipid per kg of rat body weight, GLOSt-SUV showed 4-fold more accumulation (42.4%) in the liver than control-SUV. Therefore, glycyrrhizin is considered to be a useful new ligand on liposomes for targeting to the liver. © 1991, The Pharmaceutical Society of Japan. All rights reserved.