Galactosylated proteins are recognized by the liver according to the
surface density of galactose moieties.
Nishikawa, Makiya, Chizu Miyazaki, Fumiyoshi Yamashita, Yoshinobu Takakura,
and Mitsuru Hashida.
Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences,
Kyoto University, Sakyo-ku, Kyoto 606-01, Japan
APStracts 2:0002G, 1995.
The recognition of 111In-labeled galactosylated superoxide dismutase (Gal-SOD)
and galactosylated bovine serum albumin (Gal-BSA) by the liver was
investigated in mice after intravenous injection. 111In-galactosylated
proteins were recovered in the liver by amounts, highly depending on the
degree of galactose-modification and the administered dose. The distribution
patterns were analyzed based on a physiological pharmacokinetic model
including an uptake process with Michaelis-Menten kinetics in the liver and
the hepatic plasma flow. Km of the hepatic uptake of 111In-Gal-SODs was
observed to inversely correlate with the number of galactose residues without
a significant change in Vmax and extra-hepatic clearance. This relation could
be applicable to 111In-Gal-BSA and other galactosylated proteins by using the
surface density of galactose residues as a degree of modification, suggesting
the galactose density controls the ligand-recognition by the
asialoglycoprotein receptor. The analysis also indicated that increasing the
galactose density higher than 1.0 10-3 molecule/[umlaut]u2 did not affect the
distribution of galactosylated proteins due to the limitation by the hepatic
plasma flow rate. In conclusion, efficient delivery of proteins modified with
galactose to the liver will be achieved by controlling the galactose density
on the protein surface and the administered dose.
Received 17 October 1994; accepted in final form 4 January 1995.
APS Manuscript Number G417-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995