There are limited treatment options for esophageal disorders, with patients typically receiving systemic drugs that can cause side effects. To address this, MIT engineers developed a gel-like oral drug formulation that coats the esophageal mucosa after swallowing, facilitating drug absorption through the tissue. This formulation includes a hydrogel and other key ingredients that enhance rapid drug absorption, potentially delivering antibodies like infliximab for autoimmune diseases.
"Many patients with esophageal diseases have very limited treatment options, and developing targeted drugs for this area is challenging. We hope this platform will aid in creating effective systems to help these patients," said Giovanni Traverso, associate professor at MIT and gastroenterologist at Brigham and Women's Hospital.
One common esophageal condition is eosinophilic esophagitis, an inflammation caused by food allergies that can obstruct swallowing. Crohn's disease can also inflame the esophagus, usually treated with systemic drugs, including infliximab, which neutralizes the inflammatory protein TNF-alpha. However, this immunosuppressant can increase the risk of infections and other health issues. Direct delivery to esophageal tissue could minimize these side effects, but oral drugs pass through the esophagus quickly, complicating this process.
To enhance permeability, researchers created a screening system mimicking the esophagus's structure, with esophageal tissue between two plates. Drug formulations were poured into the system to simulate ingestion, allowing measurement of how much drug penetrated the tissue.
After testing approximately 100 compounds, the most effective combination was found to be two bile salts: sodium chenodeoxycholate and sodium cholate. These salts work together to loosen the cell-cell junctions that typically hinder drug entry. They were added to a polysaccharide-derived hydrogel, which coats the esophageal lining.
In animal tests, the formulation effectively delivered infliximab to the esophagus, with temporary loosening of cell junctions returning to normal within three days. This method could help prevent side effects associated with systemic infliximab use. "If we can achieve site-directed delivery, we may mitigate systemic side effects from these immunosuppressive agents," Traverso noted.
The team is now optimizing the formulation for potential human testing, aiming for the gel to adhere long enough for drug delivery without causing discomfort. They're also exploring the possibility of using this approach for other drugs.
"This platform enables the development of drug delivery systems for the esophagus, which has not been possible before due to a lack of existing tools," Traverso added. The research was funded by the Karl van Tassel Career Development Professorship, the Department of Mechanical Engineering at MIT, and the U.S. Advanced Research Projects Agency for Health (ARPA-H).