According to the American Heart Association, strokes are the fourth leading cause of death worldwide, with ischemic strokes (those resulting from blood clots) accounting for 87% of all cases. The current treatment for breaking down the clots is a drug form of tissue plasminogen activator, an enzyme that catalyzes the formation of plasmin. Plasmin, which is also an enzyme, cleaves fibrous extra-cellular masses. Tissue plasminogen activator has been commercially available since 1987, and is remarkably effective at breaking down clots—at least in lab settings.
“Usually what happens is they reel you in, they determine you have a stroke, and if you test positive for other things, they administer the IV directly,” said Bonnecaze, a professor at the University of Texas at Austin. Bonnecaze’s research interests include rheology of suspensions and complex fluids and computational fluid mechanics. “But, interestingly, looking out over a decade of research, the efficacy is not really as good as you might expect, almost marginal . . . you ask the question, Why is this happening? Why aren’t these drugs working well? They clearly work in the lab.”
Clots, by their nature, inhibit the flow of blood to the blocked artery—thus greatly complicating drug delivery to a clot site. In this absence of direct flow, an intravenously delivered drug will have to rely on diffusion to get to an affected area, a difficulty compounded by the continuous degradation of the drug as it travels throughout the body. The reliance on diffusion also results in the need for high concentration gradients—according to Bonnecaze, a change in the clot’s distance from a main artery by a factor of three necessitates an increase in orders of magnitude of a drug’s concentration.
An artery-blocking clot can form when fatty deposits on the inside of the artery narrow the vessel’s bore. CREDIT: NIH
To counter the obstructed-flow problem, researchers at Pulse Therapeutics, a startup company in St. Louis, Missouri, began adding iron nanoparticles to the IV fluid containing the plasminogen drug. The particles are approximately 100 nanometers in diameter. When exposed to a rotating magnetic field, they begin to chain up to a length of about a micron and rotate themselves. Directed by the flow of diffusion and powered by the dipole moments of the magnetic field, these spinning microscopic rods generate a convective flow, which transports both them and the drug particles to the clot site.
After visiting Pulse Therapeutics, Bonnecaze wanted to get a better understanding about the fluid dynamics at work in the iron–particle system. Working with his graduate student Michael Clemens, Bonnecaze examined the flow dynamics at particle and vessel scale, educing that the localized vorticity created by the particles was the driving force behind the increase in flow.
“I think we have a preliminary model that explains this technique,” Bonnecaze said. “Based on this model we hope to use it to help optimize and improve the process.”
Pulse Therapeutics and Bonnecaze were recently awarded an NSF GOALI grant to create a model of the magnetically-driven transport process. Initial results look promising, Bonnecaze said.
Given the successes of a small trial conducted from 2012–13 at Box Hill Hospital in Melbourne, Australia, management at Pulse Therapeutics is also optimistic about the future of their treatment, and hopes to begin human trials in the US this year.
Future work for Bonnecaze includes examining the dynamics of the rods’ formation and role of wall interactions in their flow, with the ultimate goal of integrating it into a drug-treatment model.
John Arnst is a media services writer at the American Institute of Physics.
