title: Effect of encapsulation on plasminogen activator delivery to the microcirculation and its implications for bleeding.
abstract: OBJECTIVE
  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.
authors.affiliation: Oklahoma Bioengineering Center, University of Oklahoma, Norman, OK, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Thummala
authors.affiliation: Oklahoma Bioengineering Center, University of Oklahoma, Norman, OK, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Leach
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: E
authors.initials: E
authors.lastname: Patterson
authors.affiliation: Oklahoma Bioengineering Center, University of Oklahoma, Norman, OK, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: O'Rear
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D005342:Fibrinolysis; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology*; D006801:Humans; D061185:Mechanical Thrombolysis; D008833:Microcirculation / Q000502:physiology*; D010960:Plasminogen Activators / Q000378:metabolism*; D011817:Rabbits; D013300:Streptokinase; D015912:Thrombolytic Therapy
chemical_list: D013300:Streptokinase; D010960:Plasminogen Activators
keywords: Drug delivery; fibrinolysis; plasminogen activator; thrombolysis; transport