Capture of magnetic carriers within large arteries using external magnetic fields.
Our overall research goal is to advance the safety and effectiveness of acute ischemic stroke therapy by improving the benefit/risk ratio of thrombolysis and hence, the long-term outcome of acute ischemic stroke victims. Our approach is the development of a novel tissue plasminogen activator (t-PA) delivery system based on t-PA-loaded magnetic nano- and microcarriers 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: non-invasiveness - the magnetic t-PA carriers can be injected intravenously and targeted, as drug delivery is magnetically guided to and t-PA focally released at and within the vascular clot to induce lysis. The focus of our discussion are the two necessary, fundamental and interrelated bioengineering steps: the research and development of well-characterized, biocompatible, functionally active and t-PA-loaded (encapsulated) magnetic nano- and microcarriers able to induce effective thrombolysis, and the design of magnetic guidance systems for targeted tPA-delivery allowing also the triggered release of the thrombolytic agent at the clot site. In this paper, we theoretically demonstrated magnetic trapping of blood borne magnetic nano- and microcarriers from human large vessels, especially arteries. Then, some preliminary experiments using primate models (monkeys) were done to identify successful in vivo sequestration of magnetic carriers in large and smaller arterial branches after arterial upstream and systemic venous injection. Histology (hematoxylin-eosin stain) verified intraarterial carrier concentration (identified as black carrier agglomerates on H and E staining) at the arterial region above the surface magnet. The results revealed the feasibility of magnetic drug-targeting at arteries and solidified the proposed t-PA delivery system.
Chen
Haitao
H
Neurocritical Care and Stroke Program, Department of Neurology, The University of Chicago Medical Center, Chicago, IL, USA.
Kaminski
Michael D
MD
Pytel
Peter
P
Macdonald
Loch
L
Rosengart
Axel J
AJ
D000465:Algorithms; D000818:Animals; D001158:Arteries / Q000502:physiology*; D004337:Drug Carriers; D004339:Drug Compounding; D004574:Electromagnetic Fields; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007269:Injections, Intra-Arterial; D008252:Macaca fascicularis; D008280:Magnetics; D015233:Models, Statistical; D020521:Stroke / Q000628:therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use
D004337:Drug Carriers; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator