Affiliations: [a] Oklahoma Bioengineering Center, University of Oklahoma, Norman, OK, USA
| [b] University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Correspondence:
[*]
Corresponding author: Prof. Edgar A. O’Rear, University of Oklahoma, 100 E. Boyd SEC T301, Norman, OK 73019, USA. Tel.: +1 405 325 4379; Fax: +1 405 325 5813; E-mail: eorear@ou.edu.
Note: [1] Present address: Liberty University, 306 Liberty View Lane, Lynchburg, VA 24502, USA.
Abstract: BACKGROUND AND PURPOSE: It is known that encapsulation can alter the delivery of plasminogen activators by flow to accelerate fibrinolysis while other experimental studies suggest encapsulation may reduce the risk of hemorrhage with administration of the agent. The aim of this research is to resolve the effect of encapsulation on fibrinolysis and bleeding in the microcirculation. METHODS: An established rabbit model of fibrinolytic hemorrhage was utilized to explore the potential of encapsulation to limit bleeding. Equal dosages of free or microencapsulated streptokinase (MESK) were infused to initiate thrombolysis of small vessel clots while tracking blood loss. RESULTS: Compared to free streptokinase, significant improvements in bleeding were observed with MESK as demonstrated by (1) delayed onset of bleeding, (2) shortened duration, and (3) reduction in the volume of lost blood, consistent with less systemic fibrinogen degradation. CONCLUSIONS: Findings demonstrate that encapsulation of streptokinase can inhibit clot lysis in small vessels. Combined with prior work on accelerated thrombolysis, results suggest a time-based regimen for avoiding bleeding complications during thrombolytic therapy with encapsulated agent.
Keywords: Drug delivery, thrombolysis, transport, plasminogen activator, fibrinolysis
