Tsuji H, Osaka S, Kiwada H
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Chem Pharm Bull (Tokyo). 1991 Apr;39(4):1004-8. doi: 10.1248/cpb.39.1004.
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 mumol 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.
我们认为甘草酸是脂质体对肝脏的一种新配体，因为已知在大鼠静脉注射后约80%的甘草酸会排泄到胆汁中。为了用甘草酸修饰脂质体表面，合成了一种亲脂性甘草酸衍生物30-硬脂酰甘草酸（GLOSt）。通过核磁共振（NMR）、红外（IR）和质谱（MS）鉴定了这种新化合物的结构。由氢化卵磷脂-胆固醇-GLOSt或磷酸二鲸蜡酯（DCP）（4:4:1）制备超声处理脂质体，并用[3H]菊粉作为水性标记物进行标记。通过测量包封率和平均直径证实，含GLOSt的超声处理脂质体（GLOSt-SUV）与含DCP的对照脂质体（对照-SUV）一样均为SUV型。以每千克大鼠体重90 μmol总脂质的剂量静脉注射到大鼠体内4小时后，GLOSt-SUV在肝脏中的蓄积量比对照-SUV高4倍（42.4%）。因此，甘草酸被认为是脂质体上一种用于靶向肝脏的有用新配体。
