Encapsulation of human urokinase in rabbit erythrocytes and its disposition in the circulation system in rabbits.
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.
Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan.
Y
Y
Ito
T
T
Ogiso
M
M
Iwaki
H
H
Atago
D000818:Animals; D004337:Drug Carriers; D004355:Drug Stability; D004912:Erythrocytes / Q000201:enzymology*; D005342:Fibrinolysis / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011817:Rabbits; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood* / Q000302:isolation & purification
D004337:Drug Carriers; D014568:Urokinase-Type Plasminogen Activator