GLUCOSE-OXIDASE AS A TOOL TO STUDY IN-VIVO THE INTERACTION OF GLYCOSYLATED POLYMERS WITH THE MANNOSE RECEPTOR OF MACROPHAGES

In the present paper, we report the competition for the mannose-specific lectin of mononuclear phagocytes between two potential drug carriers, namely dextran and poly-alpha,beta-[N(2-hydroxyethyl)-D,L-aspartamide] (p-HEA) both modified by either alpha-D-mannose or beta-L-fucose residues, and glucose oxidase (G.O.) following intravenous coinjection into mice. Native dextran or p-HEA did not influence the plasma half-life time of G.O. On the other hand, coinjection of an excess of either alpha-D-mannosylated or beta L-fucosylated dextran of comparable sugar content did increase the circulation half-life time significantly. The extent by which the T1/2 of G.O. was prolonged, depended on sugar loading and the amount of competing polymer. Comparison between beta-L-fucosylated and alpha-D-mannosylated dextran revealed a slightly more efficient receptor inhibition by mannose. The effect of the macromolecular carrier nature was clearly demonstrated by comparison between dextran and p-HEA conjugates. All glycosylated p-HEA derivatives retarded the blood clearance of G.O. less than the dextran analogues. Further competition experiments revealed a rather peculiar in vivo behaviour of modified dextrans, probably due to adsorption phenomena on blood cell membranes.