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Targeted Delivery of Vascular Therapeutics

Safer, targeted drug delivery

Shear-activated nanotherapeutic
The shear-activated nanotherapeutic breaks apart and releases its drug when it encounters regions of vascular narrowing.

Vascular blockage -- which can lead to heart attacks, stroke, and pulmonary embolism -- is the leading cause of death and disability in United States and Europe. Currently, healthcare providers treat these disorders with “clot-busting” drugs, such as recombinant tissue Plasminogen Activator (tPA) -- but these drugs have a major problem. Less than 3% of the patients are treated with these therapies because the drugs have severe side effects, such as systemic bleeding. As such, these patients are at significant risk of adverse events “downstream,” including congestive heart failure, recurrent heart attacks, significant arrhythmias, premature death, and acute coronary syndrome.

The Wyss Solution

Wyss researchers have engineered a targeted “Vascular NanoRx” platform that directs and concentrates drugs at obstructed sites in blood vessels -- and requires much less tPA to work effectively and could minimize the harmful side effects of tPA. Here is how it would work:

Shear-activated nanotherapeutic
The platelet-sized Vascular NanoRx microaggregates (large blue aggregates) disperse into drug-carrying nanoparticles (blue dots) when exposed to high shear stress caused by a clot that narrows a blood vessel. View animation...

The doctor would inject a solution containing platelet-sized, biodegradable, drug-carrying “microaggregates” that break apart when they encounter high levels of shear stress, which is characteristic of a constricted blood vessel. In breaking apart, the clusters would deploy the drugs they are carrying, which then would go to work at the site of the narrowing vessel. Significantly, a recent landmark study published by the Wyss team in Science (in Resources below) demonstrated that this kind of selective targeting to the disease sites improves the drug’s efficacy at lower doses, and therefore minimizes the adverse side effects.

Potential applications:

  • Deliver drugs to targeted disease sites, breaking up vascular blockages -- with lower effective doses
  • Treatments for heart attacks, stroke, pulmonary embolism, and more
  • Deliver imaging agents to visualize disease sites in real time
  • Suppress vulnerable plaque progression with anti-inflammatories
  • Deliver drugs to prevent the formation of “scars” that can form when stents are implanted in a vessel
  • Use not only in hospital setting but also by emergency response personnel

Resource Gallery

We've won a Webby Award!

Wyss Institute is a winner of the 2012 Webby Awards in the Science category.