MEDICAL HYPOTHESES AND RESEARCH
VOL. 2, No. 3, July 2005



A. J. Rosengart, et al. [2005] Med Hypotheses Res 2: 413-424.


Magnetically Guided Plasminogen Activator-Loaded
Designer Spheres for Acute Stroke Lysis


Axel J. Rosengart*, Yumei Xie, Haitao Chen and
Michael D. Kaminski*

Neurocritical Care and Acute Stroke Program, Departments of Neurology and Surgery
(Neurosurgery), the University of Chicago and Pritzker School of Medicine, Chicago (Y.X.,
H.C., A.J.R.) and Nanoscale Engineering Group, Chemical Engineering Division, Argonne
National Laboratory, Argonne, Illinois, USA (Y.X., H.C., M.D.K.)


Abstract. Our overall research goal is to advance the safety and effectiveness of acute
ischemic stroke therapy by improving the bene¬fit/risk ratio of tissue plasminogen activator
(t-PA)-mediated thrombolysis and hence the long-term outcome of acute ischemic stroke
victims. Our approach is the development of a novel delivery system based on t-PA loaded
magnetic nano/microspheres guided directly to the site of vascular occlusion by external
magnetic fields.  Such a t-PA delivery system would conveniently combine the advantages of
both intravenous (systemic) and intraarterial (catheter-facilitated) thrombolysis, that is, it is
noninvasive ― as the magnetic t-PA carriers can be injected intravenously ― and they are
also targeted as drug delivery is magnetically-guided to and t-PA focally released at and
within the vascular clot to induce lysis. Our discussion focuses on two fundamental and
interrelated bioengineering steps: (i) the research and development of well characterized,
biocompatible, functionally active, t-PA loaded (encapsulated) magnetic nano/microspheres
able to induce effective thrombolysis, and (ii) the design of magnetic guidance systems for
targeted tPA-delivery which permit triggered release of the thrombolytic agent at the clot
site. Details of the technology are presented and the state-of-knowledge and research is
discussed.


*Address all correspondence to: Dr. Axel J. Rosengart or Dr. Michael D. Kaminski,
Neurocritical Care and Acute Stroke Program, Departments of Neurology and Surgery
(Neurosurgery), the University of Chicago, 5841 South Maryland Avenue, MC 2030,
Chicago, IL 60637, USA. Phone: 773-834-4602. Fax: 773-834-4612.
E-Mail:
arosenga@neurology.bsd.uchicago.edu


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