Busting blood clots with a nanoparticle

Experimental drug delivery may improve heart attack treatment

ORLANDO, Fla. — Nanosized gobs containing a blood clot–dissolving drug can seek out trouble spots in the body and break down blockages responsible for heart attacks, Japanese researchers reported November 14 at a meeting of the American Heart Association. The microscopic packaging seems to improve the drug’s potency and might limit its main drawback — a risk of internal bleeding — by focusing its effect at the clot.

Although the technology has been tested only in pigs, some doctors find the early results intriguing. “This could be a tremendous step forward,” said Roger Blumenthal, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore. If it tests well in people, he said, this controllable form of the clot-busting drug, called tPA, might be a boon for heart attack patients in remote areas that lack hospitals equipped to deliver the highest standard of care for heart attacks.

About half of people for whom heart attacks are fatal die before reaching a hospital and getting angioplasty, in which doctors thread a balloon-tipped catheter up to the heart to prop open blocked coronary arteries with mesh cylinders called stents. With every minute that passes after a heart attack begins, part of the heart muscle is damaged by lack of blood. “It’s one thing to have a heart attack in a metropolitan area,” Blumenthal said. “But sometimes a catheterization lab may be four hours away.” A safer form of tPA, a drug that has largely gone out of use for heart attacks in the United States because of its internal bleeding risk, could play a role In such rural areas, he said.

The Japanese team, led by cardiologist Yoshihiko Saito of Nara Medical University in Kashihara, tested a form of tPA made safer by packaging it in a coating of gelatin-based nanoparticles that prevent tPA from releasing in the blood stream.

Tests in mice showed that the nanoparticles were three times more likely than regular tPA to attach to clots, because the tiny blobs stick to a common clotting compound in the body that standard tPA doesn’t bind.

The researchers then injected either the nanoparticle drug or standard tPA into 30 pigs in which the scientists had induced blood clots. Once the nanoparticles had arrived at the clot, the researchers burst the tiny blobs with ultrasound waves and released the tPA cargo at the clot.

After 30 minutes, blood flow through obstructed vessels improved by 90 percent in pigs getting the nanoparticle drug but by only 10 percent in pigs getting standard tPA. There was also less stray tPA in the bloodstream afterward with the nanoparticles.

The new technology might expand the range of people who could administer tPA, said Robert Bonow, a cardiologist at Northwestern University School of Medicine in Chicago. Paramedics typically don’t give tPA in the United States, even to heart attack patients, because of the bleeding risk. “In theory, this would be safer,” he said.

People with pulmonary embolisms might also benefit from the nanotechnology if it succeeds in further tests, said cardiologist Vincent Bufalino of Midwest Heart Specialists in Naperville, Ill., a cardiology practice. In those patients a clot obstructs blood flow to the lungs.

Doctors use tPA for some strokes that arise when a clot jams an artery supplying the brain with blood. But that medical scenario wasn’t tested in this study.

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