Abstract: N-Lactosyl-chitosan(LCH) with different degrees of substitution(DS) of lactosyl group was synthesized and characterized with Fourier transform infrared(FTIR) and proton nuclear magnetic resonance(¹H NMR). The result of radioactive experiment in vitro shows that LCH was a specific ligand for asialoglycoprotein receptor(ASGPR) when the DS of lactosyl group ranged from 15.5% to 38.9%, which indicates LCH could be used as a novel kind of hepatic targeting carrier. Methotrexate-lactosyl-chitosan(MTX-LCH) was prepared via the following synthetic route: MTX was firstly coupled with chitosan, and then reacted with lactobionic acid to produce MTX-LCH. The DS of MTX moiety of MTX-LCH was determined via ultraviolet(UV) spectroscopy to be 5.6%, and the DS of lactosyl group to be 33.8%. MTX-LCH was water-soluble in the pH range of 1—14. The dynamic dialysis study shows that MTX-LCH was stable, and the release of MTX was very slow. These results provided a reference for the further study of liver-targeting polymeric prodrugs.

Key words: N-Lactosyl chitosan, Methotrexate, Asialoglycoprotein receptor, Liver-targeting, Polymeric prodrug