Abstract
Disposition characteristics of uricase(UC)and its conjugate with dextran derivatives were studied in mice. UC was conjugated with neutral dextran, cationic diethylaminoethyl-dextran(DEAED), or anionic carboxymethyl-dextran(CMD) with an average molecular weight of about 10, 000 by periodate oxidation. Conjugation with neutral dextran slightly accelerated the disappearance of UC which has a relatively long plasma half-life in mice. Conjugation with DEAED resulted in an extremely shorter plasma half-life and enhanced hepatic up-take and urinary excretion. On the other hand, conjugation with CMD gave a longer one than that of the native enzyme and uptake by the liver was restricted. These results suggest the biopharmaceutical properties of peptide drugs can be controlled by choosing the physicochemical properties of dextran derivatives. The usefulness of chemical modification with dextran derivatives was thus demonstrated.
