Antibacterial Implants Could Prevent Infections, Save Patients' Lives

The polymer slowly releases an antibiotic to keep bacteria from establishing a foothold. It could be used to prevent infections around such commonly used devices as catheters as well as more permanent implants, such as pacemakers, according to Buddy Ratner, UW professor of bioengineering and director of the University of Washington Engineered Biomaterials (UWEB) program.

A two-article series on the technique appears in this month's issue of the Journal of Controlled Release.

Infections linked to devices that are inserted into patients are a serious hospital problem, according to Ratner.

"People don't realize that even commonly used devices like catheters account for about 50,000 hospital deaths in the United States each year, many of them because of infection," Ratner said.

Catheters, which are used on patients who require a long regimen of intravenous drugs, are initially sterile, but they can become gathering spots for dangerous microorganisms.

"Once the bacteria get on the device, they are extremely difficult to remove and very resistant to treatment," Ratner said. "It can take 100 times the concentration of an antibiotic to kill the bacteria when they are attached as it takes to kill them when they're free."

The reason may be a protective biofilm that bacteria produce after they become established. When that happens, often the only way to treat the infection is to remove the device from the patient.

The key to stopping infections, then, lies in killing bacteria that come near the device before they form an attachment, Ratner said.

"We found a way to put the antibiotic just on the surface of the device where it interfaces with the body's fluids," he said. "What we've developed is a slowly released micro-aura of the antibiotic. It only takes a small amount because it's right where you need it."

To accomplish that, the researchers first combined the antibiotic ciprofloxacin with a polymer called polyethylene glycol - an approved food additive - and mixed that with the polyurethane used to make medical implants. That made an even, homogeneous material that released the drug in a uniform manner, Ratner said, "but the release was too quick."

To manage the rate of release, researchers used a plasma process to coat the material with an ultrathin layer of another polymer, butyl methacrylate.

When a device is implanted in the body, fluids pass through that thin, permeable outer coating and dissolve the polyethylene glycol, which makes the polyurethane porous. The antibiotic then leaches out of the polyurethane. The coating acts as a barrier to the antibiotic, controlling the rate at which it is released to the surface of the device.

"The outer coating is just 10 or 20 atoms thick," Ratner said. "It makes for a very controlled, slow release."

Tests showed that the system maintains a protective drug cloak for at least five days.

The technology has another advantage for hospital patients - it prevents the development of drug-resistant bugs when some of the bacteria are exposed to an antibiotic and survive.

"With our method, the concentration of the drug is high enough that it kills all of the bacteria that get into the zone around the device," Ratner said.

The first article of the series in the Journal of Controlled Release is co-authored by Ratner, Bioengineering Professor Thomas Horbett and UW bioengineering graduate student Connie S. Kwock in collaboration with researchers in Montana and Connecticut. The second is the work of Ratner, Kwock and Horbett