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-specif ic lectin of mononuclear phagocytes between two potential drug carrier s, namely dextran and oly-alpha,beta-[N(2-hydroxyethyl)-D,L-aspartamid e] (p-HEA) both modified by either alpha-D-mannose or beta-L-fucose re sidues, and glucose oxidase (G.O.) following intravenous coinjection i nto mice. Native dextran or p-HEA did not influence the plasma half-li fe 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. Th e extent by which the T1/2 of G.O. was prolonged, depended on sugar lo ading and the amount of competing polymer. Comparison between beta-L-f ucosylated and alpha-D-mannosylated dextran revealed a slightly more e fficient receptor inhibition by mannose. The effect of the macromolecu lar carrier nature was clearly demonstrated by comparison between dext ran and p-HEA conjugates. All glycosylated p-HEA derivatives retarded the blood clearance of G.O. less than the dextran analogues. Further c ompetition experiments revealed a rather peculiar in vivo behaviour of modified dextrans, probably due to adsorption phenomena on blood cell membranes.