[Accelerated thrombolysis by liposomal-encapsulated urokinase in a canine model of acute myocardial infarction].
We prepared liposomal-encapsulated urokinases (LEUK) by detergent removal technique. The encapsulated efficiency of urokinase (UK) was 25.6%. The LEUKs were neutral large unilamellar vesicles and its average diameter was 60.4 +/- 13.6 nm under electron microscope. Measurements of UK activity indicated about 7.1% loss of activity or leakage in tris-buffered saline over a 48 hr period at a temperature of 4 degrees C. After the same time incubation of LEUK and UK in human platelet-poor plasma (PPP) at 37 degrees C, the percentage of UK activity in LEUK group was remaining higher than that of UK group (30 min: 84.3 +/- 3.0% to 46 +/- 4%; 60 min: 60 +/- 5% to 14.9 +/- 0.8%, P < 0.01). These results suggest that liposomes preserve the thrombolytic potential of UK and that the half-life of UK in liposomes prolongs more than two times. Canine model of acute myocardial infarction was based on a thrombos obstruction. Thrombolysis tests were compared for LEUK and UK (n = 5). The time for restoring vessel patency reduced more than 50% when compared with that in UK group (28 +/- 7 min to 69 +/- 7 min, P < 0.01). The total dosage of LEUK was correspondingly lower. After one-hour thrombolysis, the fibrinogen of LEUK group (g/L) was considerably higher than that of UK group (2.5 +/- 0.5 to 1.6 +/- 0.4, P < 0.01). These results suggested that LEUK may be of practical significance in accelerating thrombolysis and reduction in bleeding complications.
Li
Z L
ZL
Division of Cardiology, Tangdu Hospital, Xi'an.
Zhang
N Z
NZ
Nie
Y H
YH
D000818:Animals; D004285:Dogs; D004337:Drug Carriers; D005260:Female; D008081:Liposomes; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage*
D004337:Drug Carriers; D008081:Liposomes; D014568:Urokinase-Type Plasminogen Activator