Engineering a better drug delivery system

Engineering is about taking a problem and solving it. Traditional medical training is about identifying a problem and using evidence-based literature to create a treatment plan. They’re not so very different, really, but when you combine these types of expertise, you get someone uniquely equipped to solve the biggest mysteries in medicine, the ones that don’t have decades of evidence-based treatments.

Carolyn Cannon, MD, PhD, is a pediatric pulmonologist who combines her education in both medicine and engineering to work on novel therapies for childhood respiratory diseases.

Cannon, who received her bachelor’s degree in bioengineering from Texas A&M, is a physician-scientist, mixing the problem-solving approach of engineering with a translational approach to research and medicine. She is exactly the type of researcher the new Engineering Medicine (EnMed) program at Texas A&M will produce—someone who can recognize the biggest health problems and think “outside of the box” to solve them.

Cannon is working to discover new therapeutics and delivery methods to fight lung infections in children and young adults living with cystic fibrosis. One approach that she finds promising involves inhaled nanoparticles, which bypass the digestive tract and thus, some of the side effects inherent in oral delivery methods. Although she focuses attention on cystic fibrosis patients, her work offers broader application for therapies aimed at preventing and treating other more common—and often life threatening—respiratory infections, as well.

Infections often become deadly when the bacterial strain is resistant to antibiotics. Cannon experienced this scenario firsthand during a fellowship in Boston.

“During my fellowship, a very transmissible strain of an unusual multidrug-resistant organism swept through the population of cystic fibrosis patients for whom I was caring,” Cannon said. “The organism, which is called Burkholderia dolosa, is so resistant that patients who picked it up had a decline in lung function and associated poor outcomes.” The organism was so unusual that there were not—and are still not—many scholarly works on it. Seeing an unmet need, Cannon—the physician—decided to dig deeper, as a scientist and an engineer.

When she set up her very first research laboratory, Cannon got to work studying the pathogenesis of the infection. Unfortunately, she came across the same resistance problem that she saw in her patients. “I couldn’t kill the bacteria in order to easily study it,” she said, “so I needed to figure out how to kill it.”

That led Cannon to look around at what investigators around country were doing to treat multidrug-resistant infections. She came across a class of silver-based antimicrobials synthesized by a chemist, Wiley Youngs, PhD, at the University of Akron. When Cannon asked for them, she received them the next day. Sure enough, it worked to kill the resistant bacteria, but it also gave her an idea for another application of the technology.

“Because the active component, silver, is small, it can go anywhere in the body quickly, including the lung where we want it,” Cannon said. “That’s what sparked the idea of trying to put silver into polymeric nanoparticles as a delivery system to help retain the silver in the lung.”

Fast forward to 2017, and Cannon has been working with Karen L. Wooley, PhD, in the Texas A&M Department of Chemistry, to develop a way to trap positively charged silver ions for delivery to the lungs and slow release. “Our overarching goal is to find new ways to treat multidrug-resistant pathogens, especially for cystic fibrosis patients who harbor these resistant bacteria in their lungs.”

An approach that is showing progress is to add inhalable ibuprofen to the silver particles. “Ibuprofen seems to enhance the antimicrobial effects of silver,” Cannon said. “They work synergistically together.” A compound made with both ibuprofen and silver would be anti-inflammatory, analgesic and antimicrobial.

Cannon is not just working in the laboratory. She goes to Texas Children’s Hospital in Houston every week to see patients as a pulmonary attending physician. She takes a somewhat unusual approach to treatment. “Because of my engineering training, I see a symptom list as a problem list of things to solve,” Cannon said. “I use the tools that are there, and if there aren’t tools, I try to create a new one.”

Once someone has a new tool, though, it needs to make it to the patient, in a long, often difficult process. Cannon sees learning about this process as one of the great benefits of EnMed. “Teaching engineers how to move their innovations into the clinic is one of the most impactful components of program,” Cannon said. “That skillset—taking something from idea to prototype to moving it into clinic—is really valuable. It’s paramount to innovate at the bench, but patients won’t benefit unless you have some mechanism to get it to the bedside.”