Zinc oxide nanopyramids show promise at preventing medical implant infections

A close-up of a pacemaker lead coated with zinc oxide nanopyramids--Courtesy of the University of Michigan

Experiments show that zinc oxide nanopyramids have the potential to become an antibacterial coating for implants like artificial joints, researchers at the University of Michigan say. Zinc oxide is a common ingredient in sunscreen, but in order to work as an effective antibiotic when placed on an implant, the team needed to modify their drug delivery.

Indeed, new drug delivery solutions are needed to combat the risk of infected devices due to the unique environment such anti-infective drugs operate within. Specific challenges include the need to selectively target foreign cells (rather than human ones), as well as the years-long lifespan of the devices that they coat.

Innovations like that under development at the University of Michigan are needed because according to an FDA meeting on the topic held last year, the 5-year survival rate of patients with infected prosthetic joints is 65%, lower than the rate for some types of cancers.

In an experiment, pegs coated with the nanopyramid formulation of zinc oxide had 95% fewer staphylococcal cells than those that were uncoated, while pegs coated with pneumonia and E. coli species were found to be less affected.

In order to break down lactose into the smaller sugars glucose and galactose, the enzyme beta-galactosidase must "twist," according to a university release. The lactose molecules position themselves in a groove in the enzyme, where amino acids come together to break lactose into glucose and galactose.

"Although more studies need to be carried out, we believe that zinc oxide nanopyramids interfere with this twisting motion," said chemical engineering professor Nicholas Kotov, who helped design the nanopyramid particles, in a statement. The nanopyramids inhibit the twisting motion by occupying the groove where the action occurs.

"While the coating was unable to completely eradicate all staphylococcal cells, this dramatic reduction could likely enable antibiotic treatments to succeed or simply allow the human immune system to take over without the need for antibiotics," said J. Scott VanEpps, a researcher in the department of emergency medicine, in a statement.

The team believes the nanopyramids were effective against staphylococcal cells (which cause staph infections like MRSA) because they bound to enzymes that make up the bacteria's cell walls, causing them to break down. Those enzymes aren't as accessible in pneumonia and E. coli species.

Luckily, human cells also do not suffer from a vulnerability to the nanopyramids' mechanism of action, which means they should not be harmed by the formulation. But the release says more research is needed to ensure that is the case; the team must also study its effects on other enzymes and bacteria.

The University of Michigan breakthrough could be a future alternative to simply coating implants in conventional antibiotics, as is currently done, and demonstrates the importance of geometry and shape when it comes to the effectiveness of drug delivering nanoparticles.

More details are available in papers published in Nanomedicine: Nanotechnology, Biology and Medicine and ACS Nano.

Supporters of the research include the U.S. National Science Foundation, the U.S. National Institutes of Health, the National Research Foundation of Korea and the Society for Academic Emergency Medicine.

- read the university news release
- here's the abstract in Nanomedicine | here's the abstract in ACS Nano

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