Could Carbon Monoxide Foam Help Fight Inflammation? | MIT News

Carbon monoxide is best known as a potentially deadly gas. In small doses, however, it also has positive properties: it has been shown to reduce inflammation and can stimulate tissue regeneration.

A team of researchers led by MIT, Brigham and Women’s Hospital, the University of Iowa and Beth Israel Deaconess Medical Center has now developed a novel way to get carbon monoxide into the body while bypassing its potentially dangerous effects. Inspired by techniques used in molecular gastronomythey were able to incorporate carbon monoxide into stable foams that can be delivered to the digestive tract.

in the a study in mice, the researchers showed that these foams reduced inflammation of the colon and helped reverse acute liver failure caused by a paracetamol overdose. The new technique described today in a Science Translational Medicine Paper, could also be used to deliver other therapeutic gases, the researchers say.

“The ability to deliver a gas opens up completely new possibilities for how we think about therapeutics. We don’t generally think of a gas as a therapeutic that you would take orally (or that could be given rectally), so this provides an exciting new way to think about how we can help patients,” says Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT and Gastroenterologist at Brigham and Women’s Hospital.

Traverso and Leo Otterbein, professor of surgery at Harvard Medical School and Beth Israel Deaconess Medical Center, are the senior authors of the paper. The lead authors are James Byrne, University of Iowa Physician, Scientist and Radiation Oncologist (Formerly Resident in the Mass General Brigham/Dana Farber Radiation Oncology Program) and Research Fellow at MIT’s Koch Institute for Integrative Cancer Research; David Gallo, researcher at Beth Israel Deaconess; and Hannah Boyce, research engineer at Brigham and Women’s.

Delivery by foam

Otterbein has been investigating the therapeutic effects of low doses of carbon monoxide since the late 1990s. The gas has been shown to have beneficial effects in preventing transplant organ rejection, reducing tumor growth, and modulating inflammation and acute tissue injury.

When carbon monoxide is inhaled in high concentrations, it binds to hemoglobin in the blood and prevents the body from getting enough oxygen, which can lead to serious health problems and even death. At lower doses, however, it has positive effects like reducing inflammation and promoting tissue regeneration, Otterbein says.

“We have known for years that carbon monoxide can have beneficial effects in all types of medical conditions when administered as an inhaled gas,” he says. “However, it has been challenging to use in the clinic for a number of reasons related to safe and reproducible administration and concerns of healthcare workers, which has led to people looking for other ways to administer it .”

A few years ago, Traverso and Otterbein were introduced by Christoph Steiger, a former MIT postdoc and author of the new study. Traverso’s laboratory specializes in developing novel methods for delivering drugs to the gastrointestinal tract. To overcome the challenge of providing a gas, they came up with the idea of ​​incorporating the gas into a foam, much like how chefs use carbon dioxide to make foams infused with fruit, vegetables, or other flavors.

Culinary mousses are usually made by adding a thickening agent or gelling agent to a liquid or pureed solid and then either whipping it to trap air or using a special siphon that injects gases such as carbon dioxide or compressed air.

The MIT team developed a modified siphon that could be attached to any type of gas canister, allowing them to incorporate carbon monoxide into their foam. To make the foams, they used food additives like alginate, methylcellulose, and maltodextrin. Xanthan gum has also been added to stabilize the foams. By varying the amount of xantham gum, the researchers were able to control how long it would take for the gas to be released once the foams were administered.

After showing that they could control the timing of gas release in the body, the researchers decided to test the foams for a few different uses. First, they studied two types of topical applications, analogous to applying a cream to soothe an itchy or inflamed area. In a study in mice, they found that administering the foam rectally reduced inflammation caused by colitis or radiation-induced proctitis (inflammation of the rectum that can be caused by radiation treatment for cervical or prostate cancer).

Current treatments for colitis and other inflammatory diseases like Crohn’s disease usually involve drugs that suppress the immune system, which can make patients more susceptible to infections. Treating these conditions with a foam that can be applied directly to inflamed tissue offers a potential alternative or complementary approach to these immunosuppressive treatments, the researchers say. While the foams were given rectally in this study, it might also be possible to give them orally, the researchers say.

“The foams are so easy to use, which will help translate to patient care,” Byrne says.

dose control

The researchers then set out to investigate potential systemic uses, where carbon monoxide could be delivered to distant organs such as the liver, due to its ability to diffuse from the gastrointestinal tract to other sites in the body. For this study, they used a mouse model of a paracetamol overdose that causes severe liver damage. They found that gas released into the lower gastrointestinal tract could reach the liver and greatly reduce the levels of inflammation and tissue damage seen there.

In these experiments, the researchers found no adverse effects after carbon monoxide administration. Previous human studies have shown that small amounts of carbon monoxide can be safely inhaled. A healthy person has a carbon monoxide concentration of about 1 percent in the bloodstream, and human volunteer studies have shown that levels of up to 14 percent can be tolerated without side effects.

“We think that with the foam used in this study, we’re not even close to reaching the levels that would worry us,” says Otterbein. “What we learned from the inhalant gas trials paved the way to saying it’s safe as long as you know and can control how much you’re giving, much like any drug. That’s another nice aspect of this approach – we can control the exact dose.”

In this study, the researchers also made gels containing carbon monoxide, as well as gas-filled solids, using techniques similar to those used to make pop rocks, the hard candies containing pressurized bubbles of carbon dioxide. They plan to test these in further studies and develop the foams for possible testing on human patients.

The research was funded in part by a Young Investigator Award from the Prostate Cancer Foundation, a US Department of Defense Early Investigator Award for prostate cancer, a Hope Funds for Cancer Research grant, the National Football League Players Association, the US Department of Defense, and MIT’s Mechanical Engineering Division .

Comments are closed.