MIT Engineers Develop Gel Coating for Direct Drug Delivery to the Esophagus
Key Insights
MIT researchers have created a hydrogel-based oral formulation that coats the esophageal lining, enabling direct drug delivery to a historically difficult-to-target tissue.
The formulation combines a polysaccharide hydrogel with bile salts (sodium chenodeoxycholate (search) and sodium cholate (search)) that temporarily loosen cell-cell junctions to enhance drug permeability.
In animal studies, the gel successfully delivered infliximab, an anti-TNF-alpha (search) antibody, directly to esophageal tissue, with cell junctions returning to normal within three days.
MIT engineers have developed a novel gel-like oral drug formulation capable of coating the mucosal lining of the esophagus and delivering therapeutic antibodies directly through the tissue, addressing a longstanding challenge in treating esophageal disorders. The research, published in Nature Biomedical Engineering, represents what the team describes as a platform technology that could expand treatment options for patients with conditions such as eosinophilic esophagitis (search) and Crohn's disease (search)-related esophageal inflammation.
"There are many people with esophageal disease, and if you look at drugs for these conditions, they're very limited in their ability to target this part of the body and it's very difficult to develop them," said Giovanni Traverso, associate professor of mechanical engineering at MIT, gastroenterologist at Brigham and Women's Hospital, and senior author of the study. "We hope this platform will make it easier to develop systems that can help patients suffering from these conditions."
The Challenge of Esophageal Drug Delivery
Delivering drugs directly to the esophagus has proven inherently difficult. Oral medications pass through the esophagus too quickly for meaningful absorption, and the tissue itself is lined by stratified squamous epithelium — a layer highly impermeable to drugs. Current treatment for esophageal inflammatory disorders typically relies on systemic drugs, which can produce unwanted side effects.
Infliximab, an antibody that neutralizes the inflammatory protein tumor necrosis factor alpha (TNF-alpha (search)), is commonly used to treat these conditions. However, as an immunosuppressant, systemic administration carries an elevated risk of infections and other health complications. Injecting drugs directly into esophageal tissue is an alternative, but the procedure is uncomfortable for patients and requires in-office visits. An anti-inflammatory steroid formulated as a thick mixture exists, yet it still struggles to penetrate the impermeable squamous layer.
Screening for Permeability Enhancers
To overcome the permeability barrier, the research team designed a screening system that mimics esophageal structure, with tissue pressed between two vertical plates. Drug formulations poured into the top simulate oral ingestion, and researchers measure how much drug passes through to collection wells below.
Using this system, the investigators screened approximately 100 different excipients — inactive ingredients that enhance drug effects — and identified top candidates. Testing pairs of these compounds revealed that the most effective combination was two bile salts: sodium chenodeoxycholate (search) and sodium cholate (search).
"The hydrogel helps the formulation remain on the esophageal surface for longer, while the bile salts help increase transport across the tissue," said Christina Karavasili, former MIT postdoc, now assistant professor at Aristotle University of Thessaloniki, and the paper's lead author. "Our data suggest that the bile salts temporarily loosen these cell–cell junctions, mainly by interacting with calcium ions that help maintain junction integrity. This creates a more permissive pathway between the cells, allowing larger molecules to move into the mucosal tissue more efficiently."
The bile salts were incorporated into a polysaccharide-derived hydrogel, whose viscous consistency allows it to lightly coat the esophageal lining after swallowing.
Preclinical Results and Safety
In animal studies, the formulation effectively delivered infliximab directly to esophageal tissue. Critically, the loosening of cell-cell junctions was temporary, with cells returning to normal within three days — an important safety consideration for potential clinical translation.
"We were interested in delivering anti-TNFs as a model drug, but also to help people who suffer from conditions like Crohn's disease (search) to have options that could be delivered to the site," Traverso said. "If we have the possibility of site-directed delivery, we may be able to mitigate systemic side effects from these immunosuppressing agents."
Next Steps Toward the Clinic
The researchers are now optimizing the formulation for potential human testing. A key objective is ensuring the gel adheres long enough to deliver therapeutic payloads without causing patient discomfort. The team is also exploring the feasibility of using this approach to deliver other types of drugs, including small molecules and additional antibody-based therapies.
"This is a platform to enable the development of drug-delivery systems for the esophagus, which hasn't been possible before because the tools haven't existed," Traverso said.