Liver targeting characteristics of galactosyl poly L lysine

The liver targeting characteristics of galactosyl poly L lysine (GalPLL) synthesized by reductive lactosamination were firstly investigated in mice using radioisotope tracing assay. The results showed that GalPLL was highly liver targeting and its distribution pattern in vivo was similar to that of asialofetuin, a native ligand of asialoglycoprotein receptor (ASGPR) on hepatocytes. The intravenously injected [ 125 I]GalPLL was mainly taken up by the liver, and the maximal liver uptake was 38.9% of the total injected dose at 5 min after injection. The maximal liver uptake of [ 125 I]GalPLL was 5.7 fold higher than that of human serum albumin. The liver uptake of [ 125 I]GalPLL could be specifically inhibited by asialofetuin and non labeled GalPLL but not the same poly L lysine without galactosylation, indicating that they were taken up into liver by ASGPR mediated endocytosis. So galactosyl poly L lysine seems to be a promising carrier in liver targeting delivery of drugs or genes as regards to its high liver targeting ability and many other advantages in respect of its synthesis and utility over the native ligands of ASGPR.