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Alternating layers of drugs with layers of a biodegradable polymer, rather than mixing polymer and drug and slathering the mixture on an implant, results in a thinner coating that contains a higher proportion of the drug—as much as 50 percent, rather than the more usual 4 percent. And these coatings can be produced at low temperatures and in water, rather than in the harsh conditions usually required for polymer processing. This means they’re compatible with a broader range of delicate molecules including protein drugs and therapeutic RNA.

“What distinguishes this technology is the promise of being able to release different drugs sequentially, in a controlled way,” says Myron Spector, professor of orthopedic surgery at Harvard Medical School. Patients who have a poor vascular system that can compromise bone growth, including diabetics and heavy smokers, might benefit from coatings that release drugs to stimulate bone formation or blood-vessel growth, in addition to antibiotics.

The permanent layer of antimicrobial polymer on which Hammond builds the drug-releasing films was previously developed by Alexander Klibanov, a professor of chemistry at MIT. “When these polymers are present on a surface, bacteria will die on impact—the polymer disrupts the cell membrane, and the bacteria’s guts spill out,” says Hammond. When submerged in a solution of staph bacteria for two weeks, a different substrate untreated with the layers of antibiotics was completely colonized by bacteria by the end of the first hour. No bacteria took hold on a surface of Klibanov’s polymer treated with Hammond’s films over the two-week period, even after the drug-releasing layers degraded. This work was published online in the Journal of the American Chemical Society in November.

Spector has worked with Hammond on preliminary studies of the coatings in animals and will now work with the MIT group to demonstrate whether they do improve outcomes after a joint replacement. Miller of the University of California, who has worked on antimicrobial implants in animals, notes that many factors remain unknown. For example, “we don’t know for how long we want a drug to be released,” he says. Further tests should make this clearer.

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Credit: JACS/ACS

Tagged: Biomedicine, Materials, polymers, antibiotics, biomaterial, infection, medical implants

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