Pharmaceutical Research

, Volume 33, Issue 7, pp 1552–1563 | Cite as

An In Vitro Thrombolysis Study Using a Mixture of Fast-Acting and Slower Release Microspheres

  • Hoai X. Nguyen
  • Edgar A. O’Rear
Research Paper



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.


chitosan encapsulation eudragit reocclusion thrombolysis 







Encapsulation efficiency


Eudragit FS30D


Fourier transform infrared


2-(N-morpholino)ethanesulfonic acid




Plasminogen activator


Plasminogen activator inhibitor


Phosphate-buffered saline


Polyethylene glycol


Platelet-poor plasma


Platelet-rich plasma


Poly(vinyl alcohol)


Scanning electron microscope




Transmission electron microscope


Tissue-type plasminogen activator



The authors gratefully acknowledge Dr. Preston Larson and Greg Strout from the Samuel Roberts Noble Electron Microscopy Laboratory at the University of Oklahoma for technical assistance with the SEM and TEM experiments. We are also grateful to Evonic Röhm for supplying Eudragit FS30D.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.School of Chemical, Biological and Materials EngineeringUniversity of OklahomaNormanUSA
  2. 2.University of Oklahoma Biomedical Engineering CenterNormanUSA

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