Doses by Design

Each year, hundreds of thousands of Americans receive hip, knee, or other orthopedic implants. Typically, these implants last only about 10 years, says associate professor of chemical engineering Paula Hammond ‘84, PhD ‘93, and they are frequently replaced even sooner due to infection. Such a secondary replacement is “a bit of a big deal,” says Hammond, often requiring a patient to go without a joint entirely for as long as a few months while his or her infection is treated. Hammond thinks she can help avoid implant-site infections, thanks to a novel method for coating implants with very thin layers of several drugs that can be engineered to dissolve into the body on a predetermined schedule.

Delivery systems made from currently available polymers can release drugs in the body slowly, over long periods, but they can handle only one drug at a time. Hammond’s method, by contrast, involves depositing very thin films of oppositely charged drugs, one atop another. Each layer can be as thin as .5 nanometers and can be tailored to dissolve in the body at a specific rate. Once one layer has dissolved, release of the drug beneath it begins. Researcher David Lynn laid the groundwork for this delivery technique several years ago, when he was a postdoc in the lab of chemical- and biomedical-engineering professor Robert Langer. Lynn created a “library” of thousands of polymers that are both charged, so they can be incorporated into a film, and degradable, so that drugs embedded in the film can be released into the body. “[The polymers] became very easy to make, they were very cheap, and there were tons of them we could try,” says Kris Wood, a chemical-engineering graduate student working with Hammond. Now, Hammond’s group is using these polymers to make films that dissolve over the course of days, weeks, or even months, as needed.

Eventually, Hammond hopes to develop a film of at least three layers that will release drugs that address typical problems related to joint replacements. The outermost layer would release an antimicrobial to prevent infection; beneath it might be a drug that encourages the growth of blood vessels around the implant; and the last layer would include a drug that encourages bone growth. Sequential delivery is crucial in this case. “If we tried to introduce all of these [drugs] at once, it would be detrimental to bone regrowth,” says Hammond.

Hammond foresees other applications for the method as well, including medicated sutures, drug-coated implants for localized cancer treatment, and medicated contact lenses to aid the recovery of people who have had eye surgery. “We all hate eyedrops to begin with, and when you’re 75 and you’re dealing with this, it’s a big pain…. We can create very thin films that can administer drugs at least for those first several days post surgery. And that would get rid of what they call ‘patient error,’ which means they didn’t put [the drops] in,” says Hammond.

The researchers have already shown that the method works for two layers of model drugs; this summer, they hope to begin tests to show the viability of using the drugs in orthopedic implants, and then start adding more layers of drugs. – By Lisa Scanlon