A California company believes it has found a way to alleviate a vexing problem with existing medical stents: the formation of blood clots caused by drug coatings. Conor Medsystems of Menlo Park is currently testing a new design that incorporates tiny holes for drugs and the dissolvable polymer mixtures that hold them in place.
Each year, bare-metal stents are implanted in the coronary arteries of 800,000 Americans, and hundreds of thousands of people worldwide. Stents act as physical supports that help keep an artery open. Most stents used in the United States and Europe are fully coated with a polymer that’s pre-impregnated with drugs, often an anti-scarring or anti-inflammatory medication. But the mix of drugs and polymers tends to diffuse into the bloodstream at an unpredictable rate. And arterial areas are sensitive, so that medications need to be released in a controlled fashion.
Researchers at Conor believe they can control drug release by putting the drug and polymer compound into tiny gaps in a stent, instead of coating the whole device with the mix. Along the branches of Conor’s metal stents are hundreds of small holes (100 microns long, 125 microns wide, and 100 microns deep). Each tiny gap acts as a reservoir for a drug-and-polymer mix. Furthermore, the mix can be altered from one reservoir to the next, allowing a highly controlled release of different medications, says the company’s founder and chief technology officer, John Shanley.
“Instead of having just one polymer coating holding all the drugs being delivered,” he says, “you can have different ones that are specifically compatible with the drug you are seeking to have dissolved into the patient. It opens up your ‘tool box’ to many other polymers, most with safer properties.”
Conor’s stents are made from both stainless steel and cobalt chrome alloy, materials that give them the flexibility to be coiled like springs before insertion, usually through an artery in the patient’s thigh. And the wells are etched into the stents using a proprietary technology. Finally, robotic devices guide tiny syringes holding various drug and polymer cocktails, which fill the wells with pinpoint accuracy.
Drug-coated stents were first approved in the United States in the late 1990s and now dominate the global market. They became so popular because their ability to deliver drugs directly to a site made them less likely to induce an unpleasant side effect of earlier stents: they’d become clogged by smooth muscle cells and cellular debris. Indeed, in nearly 30 percent of bare-metal coronary stentings conducted as recently as 2000, patients required a repeat balloon angioplasty procedure to clear the blocked area of cellular deposits.
With drug-coated stents, known as drug-eluting stents, such repeat procedures dropped to the single digits. But recent studies have indicated that drug-eluting stents also have problems. In March, a study by University Hospital in Basel, Switzerland, found that drug-and-polymer-coated stents were continuing to release anti-scarring drugs into a patient’s arterial walls long after the therapy was no longer required. The result, according to the study, was effectively to create an open wound in the artery beside the stent that contributed to platelet clotting, and ultimately to thrombosis-related heart attacks.
The coating polymers may also be suspect: they have to be far more robust than the compounds used in Conor’s reservoir-laced stents in order to withstand the friction that comes with inserting the stent into a patient. With the new stent design, the polymers aren’t exposed to friction because they sit, slightly recessed, in the stents’ reservoirs.
“Some people feel the polymers themselves are the problem, that when they break down they might have a negative effect on the vascular system,” explains James Barry, vice president of corporate research and advanced technology development at Boston Scientific in Natick, MA, one the nation’s two largest stent makers.
Last month, the Wall Street Journal conducted an informal survey of U.S. cardiologists, reporting that many of them were worried enough about clots and thrombosis to curtail the use of the coated stents. Hence, the push for a new stent design has picked up momentum.
“I am an absolute believer in the virtues of reservoirs for drug delivery,” says John Santini Jr., founder and president of MicroChips in Bedford, MA. One of those virtues, Santini notes, is that the drugs can be mixed into compounds as simple and biologically friendly as thickened glucose, instead of complex polymers.
Other manufacturers are also working on addressing the concerns with polymer-coated stents. Boston Scientific is in the early stages of developing a polymer-free stent that uses “nano-porous markings and torturous channels” etched along the device’s metal struts to hold drugs in place, says Barry. In theory, such devices, he says, would allow micrograms of drugs in a liquid, polymer-free suspension to settle into the tiny carved channels. After the stent is inserted, the drugs would “find their way” out of the stent and into the artery, he says, much the way water flows out of a sponge.
Conor Medsystems expects current U.S. trials of its CoStar stent, involving 1,700 volunteers, to be completed by spring 2007. If they’re successful, the reservoir stent could hit the American market next year, Shanley says.
“Think of those tablets you used to make paints for Easter eggs,” he says. “The way the color would dissolve into the water is a similar idea. What we want is to make the drugs dissolve safely in the same way, but at rates we can control.”