Magnetically guided plasminogen activator-loaded designer spheres for acutestroke lysis.

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. It is noninvasive, as the magnetic t-PA carriers can be injected intravenously, and they are also targeted, as the drug is magnetically-guided to and 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.