Inspired by how coffee shops foam milk, as well as gummy candy and sizzling Pop Rocks, researchers have designed three gas-trapping materials to deliver a low dose of carbon monoxide into the body to potentially treat gastrointestinal disorders.
Carbon monoxide is fatal when inhaled at high concentrations, but the team’s results, published in Science Translational Medicine on Wednesday, showed that the three systems — using foam, a hydrogel, and a solid — can effectively deliver carbon monoxide in mice. The foam method was found to reduce tissue injury and inflammation in mouse models of chemically induced colitis, radiation-induced proctitis, and liver injury due to acetaminophen overdose, and also tested in pigs.
The foam gas-entrapping material, or GEM, was inspired by the whipping siphons used at Starbucks, said James D. Byrne, first author on the study and now an assistant professor of oncology and biomedical engineering at University of Iowa Health Care. The researchers crafted their own whipping siphon and pressurized it up to 200 psi, almost seven times the pressure of a car tire. They were able to trap carbon monoxide gas inside little bubbles in the foam GEM.
Because the contraption is simply a pressurized system, it can be easily transported and used in different parts of the world, said Byrne, who worked on the study as a postdoctoral researcher at the Massachusetts Institute of Technology. The team also tested a gel to trap carbon monoxide, using what Byrne described as “ionic crosslinker sodium alginate within calcium chloride solution” — in other words, a gummy-bear-type system.
“One of the key goals from the outset was really to use source reagents or ingredients that are low cost, one for scalability and for a product to be viable not just efficacious,” said Giovanni Traverso, assistant professor in the department of mechanical engineering at MIT and co-corresponding author.
Finally, the team went on YouTube to see how Pop Rocks were made, and applied the same strategy to make solid GEMs that would allow for controlled carbon monoxide release in the gut.
While it is toxic at high levels, carbon monoxide is becoming accepted as a potential therapeutic that can modulate inflammation, said Leo E. Otterbein, professor of surgery at Beth Israel Deaconess Medical Center and the other co-corresponding author.
Inhaled carbon monoxide was shown to help patients with respiratory distress and is being tested on patients with lung disease in ongoing clinical trials. There are “30 people walking around who were treated with carbon monoxide during their kidney transplants,” he added.
Since the rectally administered foam delivers carbon monoxide directly to the affected areas of the gastrointestinal system, this reduces the amount of CO needed. The team found that the carbon monoxide could alleviate gut damage and colon inflammation. Then, since blood from the gut drains into the liver, they found that it could also address liver inflammation.
“Every therapeutic, including food or water, is toxic when taken at certain levels,” Traverso said. “It’s important to recognize that when delivered or administered appropriately, things can also have benefits.”
Producing adequate amounts of the foam for humans and ensuring it meets the Food and Drug Administration’s safety standards will take some more work, said Joseph Onyiah, an assistant professor of gastroenterology at the University of Colorado School of Medicine who was not involved with the study.
The researchers next plan to crank up the whipping siphon pressure to trap and release more carbon monoxide with more smaller bubbles inside the foam. This would reduce the volume of material that needs to be delivered to patients.
“We give rectal formulations all the time, and they’re generally well-tolerated by patients, but they don’t necessarily want to stay in them indefinitely,” Onyiah said, emphasizing the need for more testing to perfect a longer-acting and ideally once-daily formulation.
Researchers say the foam can be delivered rectally or orally. And the GEM has applications far beyond the gut. Otterbein noted that trapped gasses can be useful for the Department of Defense when, for example, it needs to deliver oxygen cylinders over long distances to the front lines of a conflict.
“I’m impressed by the innovative approach combining traditional research with techniques using gastronomy to come up with a viable product,” Onyiah said. “It’s out of the box.”
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