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The application and usefulness of resealed erythrocytes as cell carriers of human urokinase (UK) were studied in rabbits. UK purified by affinity chromatography were used to load erythrocytes by a dialysis method. The amount of UK entrapped in the erythrocytes was 2064 +/- 416 IU per ml of packed cells, with efficiency of encapsulation being 20.0 +/- 4.2%. When the UK loaded erythrocytes were incubated in Hank's solution or rabbit plasma for 3 h at 37 degrees C, the UK activities in the resealed cells declined similarly to first-order kinetics. The UK activities released into Hank's solution increased cumulatively during the incubation but those in plasma decreased after a peak concentration at 15 min. After i.v. administration of free UK, the activity decreased according to a biexponential function, suggesting its uptake in the liver and kidney and the formation of UK-proteinase inhibitor complexes and the in vivo decline of UK in loaded cells also indicated a biexponential kinetics. The AUC ratio of UK after an intravenous injection of the loaded erythrocytes was calculated to be about 8.0%. These results indicated that the UK loaded erythrocytes may be useful as a dosage form for treatment of patients with thrombosis.

Encapsulation of human urokinase in rabbit erythrocytes and its disposition in the circulation system in rabbits.