title: An In Vitro Thrombolysis Study Using a Mixture of Fast-Acting and Slower Release Microspheres.
abstract: To test the hypothesis that a mixture combining fast and slower release rate microspheres can restore blood flow rapidly and prevent formation of another blockage in thrombolysis.
  
  
  
  We used polyethylene glycol (PEG) microspheres which provide the release of the encapsulated streptokinase (SK) on the scale of minutes, and Eudragit FS30D (Eud), a polymethacrylate polymer, for development of delayed release microspheres which were desirable to prevent a putative second thrombus. Eud microspheres were coated with chitosan (CS) to further extend half-life. Experiments included the development, characterization of Eud/SK and CS-Eud/SK microspheres, and in vitro thrombolytic studies of the mixtures of PEG/SK and Eud /SK microspheres and of PEG/SK and CS-Eud/SK microspheres.
  
  
  
  CS-Eud/SK microspheres have slightly lower encapsulation efficiency, reduced activity of SK, and a much slower release of SK when compared with microspheres of Eud/SK microspheres. Counter-intuitively, slower release leads to faster thrombolysis after reocclusion as a result of greater retention of agent and the mechanism of distributed intraclot thrombolysis.
  
  
  
  A mixture of PEG/SK and CS-Eud/SK microspheres could break up the blood clot rapidly while providing clot-lytic efficacy in prevention of a second blockage up to 4 h.
authors.affiliation: School of Chemical, Biological and Materials Engineering, University of Oklahoma, 100 E. Boyd, SEC, T301, Norman, Oklahoma, 73019, USA.|University of Oklahoma Biomedical Engineering Center, Norman, Oklahoma, 73019, USA.
authors.forename: Hoai X
authors.initials: HX
authors.lastname: Nguyen
authors.affiliation: School of Chemical, Biological and Materials Engineering, University of Oklahoma, 100 E. Boyd, SEC, T301, Norman, Oklahoma, 73019, USA. eorear@ou.edu.|University of Oklahoma Biomedical Engineering Center, Norman, Oklahoma, 73019, USA. eorear@ou.edu.
authors.forename: Edgar A
authors.initials: EA
authors.lastname: O'Rear
mesh_terms: D048271:Chitosan / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D005343:Fibrinolytic Agents / Q000737:chemistry* / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008863:Microspheres; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D013300:Streptokinase / Q000737:chemistry* / Q000494:pharmacology; D015912:Thrombolytic Therapy / Q000379:methods; D013927:Thrombosis / Q000188:drug therapy*
chemical_list: D005343:Fibrinolytic Agents; D011108:Polymers; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D011092:Polyethylene Glycols; D048271:Chitosan; D013300:Streptokinase
keywords: chitosan; encapsulation; eudragit; reocclusion; thrombolysis