Abstract
Superoxide dismutase(SOD)is a hopeful candidate as a therapeutic agent against inflammatory disease. However, for such use a serious drawback must be overcome, i. e., exogenously supplied SOD fails to exhibit activity in vivo mainly due to its short half-life. To increase the half-life of the enzyme, we conjugated SOD with a copolymer of divinyl ether and maleic anhydride (DIVEMA). The half-life of DIVEMA-SOD was examined in vitro and in vivo based on the enzymatic activity of SOD. The enzymatic activity of SOD decrease to 50% within 139 min in human plasma in vitro. On the contrary that of DIVEMA-SOD showed no decrease in 24 hrs. Afte injection of mice with the enzyme via a caudal vein, blood was collected periodically, and the serum was examined for its SOD activity. SOD injected alone lost 50% of its activity within 6 min, whereas DIVEMA-SOD showed a biphasic decrease in activity, with the half-life of the β phase being 69 min. Pharmacokinetic analysis revealed that the AUC (area under the curve) of DIVEMA-SOD was 5.8 times greater than that of SOD. Such dramatic improvement of the phamacokinetic parameters should contribute to the increased anti-inflammatory activity of DIVEMA-SOD in vivo.
