Thrombolysis using liposomal-encapsulated streptokinase: an in vitro study.
The clot-lysing ability of streptokinase (SK) was examined using membrane-bound thrombi. Encapsulation of SK in large unilamellar phospholipid vesicles (liposomes) resulted in entrapping approximately 30% of its original activity. Measurements of streptokinase activity for liposomal-encapsulated streptokinase (LESK) indicated little loss of activity or leakage in Tris-buffered saline over a 24-hr period at temperatures of 4 and 23 degrees C. However, incubation of free SK and LESK in platelet-poor plasma (PPP) at 37 degrees C resulted in a decrease of SK activity. The retention of SK activity in LESK was considerably higher than that of unentrapped SK. Clot-dissolving time (CDT) was measured by monitoring the pressure drop during slow filtration in plasma through membrane-bound thrombi. The results indicated that both LESK and free SK were able to activate the fibrinolytic system. Without prior incubation in PPP at 37 degrees C, the CDT of a SK and PPP mixture (SK/PPP) was 10.7 +/- 1.9 min (n = 12), while that of a LESK and PPP mixture (LESK/PPP) was 12.4 +/- 1.7 min (n = 12). The CDT-detected clot-lysing abilities of both SK and LESK were diminished by incubation in PPP, but to different extents. After 15- and 30-min incubations, the CDT of SK/PPP increased significantly to 15.5 +/- 1.5 and 24.1 +/- 2.4 min (n = 5, P less than 0.05), respectively. In contrast, the CDT of LESK/PPP increased to 13.3 +/- 0.8 min (n = 5) after 15 min of incubation and to 16.0 +/- 1.1 min (n = 5, P less than 0.05) after a 30-min incubation. These results suggest that entrapment of SK in liposomes preserves the thrombolytic potential of the plasminogen activator by limiting its exposure to the components of the plasma.
Nguyen
P D
PD
Department of Chemical Engineering, University of Oklahoma, Norman 73019.
O'Rear
E A
EA
Johnson
A E
AE
Lu
R
R
Fung
B M
BM
D000328:Adult; D004355:Drug Stability; D005342:Fibrinolysis / Q000187:drug effects; D005374:Filtration; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D010316:Particle Size; D010960:Plasminogen Activators; D013300:Streptokinase / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D015912:Thrombolytic Therapy
D008081:Liposomes; D013300:Streptokinase; D010960:Plasminogen Activators