Ogawara K, Nishikawa M, Takakura Y, Hashida M
Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
J Control Release. 1998 Jan 2;50(1-3):309-17. doi: 10.1016/s0168-3659(97)00157-0.
Hepatic uptake of 111In-labelled galactosylated bovine serum albumin (Gal-BSA) with different number of galactose residues per BSA were studied in rat liver perfusion experiments. During a single-pass constant infusion mode, [111In]Gal-BSAs (0.1-2.0 micrograms/ml) were continuously extracted by the liver and its extraction ratio at steady-state (Ess) was lowered as the inflow concentration increased. Hepatic clearance of [111In]Gal-BSAs increased significantly according to the increase in the number of galactose residues per BSA at an inflow concentration of 0.7 micrograms/ml. The outflow patterns of [111In]Gal-BSAs at various inflow concentrations were simultaneously fitted to a one-organ pharmacokinetic model, by which we can characterize their binding to the cell surface and internalization processes separately. The parameters obtained were varied significantly among [111In]Gal-BSAs depending on the number of galactose residues and indicate that not only the binding to the receptors but also the internalization after the binding are regulated by the number of galactose residues per BSA during hepatic uptake.
在大鼠肝脏灌注实验中，研究了每分子牛血清白蛋白（BSA）上具有不同数量半乳糖残基的111In标记的半乳糖基化牛血清白蛋白（Gal-BSA）的肝脏摄取情况。在单次通过恒速输注模式下，肝脏持续摄取[111In]Gal-BSAs（0.1 - 2.0微克/毫升），且随着流入浓度的增加，其稳态提取率（Ess）降低。在流入浓度为0.7微克/毫升时，[111In]Gal-BSAs的肝脏清除率随着每分子BSA上半乳糖残基数量的增加而显著增加。将不同流入浓度下[111In]Gal-BSAs的流出模式同时拟合到一个单器官药代动力学模型中，通过该模型我们可以分别表征它们与细胞表面的结合以及内化过程。根据半乳糖残基数量的不同，[111In]Gal-BSAs获得的参数有显著差异，这表明在肝脏摄取过程中，不仅与受体的结合，而且结合后的内化都受到每分子BSA上半乳糖残基数量的调节。
