People with esophageal disorders have limited treatment options due to the challenge of delivering drugs directly to this body part. Patients typically receive systemic drugs, which can cause unwanted side effects. To address this issue, MIT engineers have created a gel-like oral drug formulation that coats the esophagus’s mucosal lining when swallowed, enabling drugs to penetrate the tissue.<\/p>\n
This formulation, which includes a hydrogel and essential components for rapid drug absorption, may deliver antibodies like infliximab, used for autoimmune diseases, or other antibodies and small-molecule drugs. “There are many people with esophageal disease, and if you look at drugs for these conditions, they\u2019re very limited in their ability to target this part of the body and it\u2019s very difficult to develop them. We hope this platform will make it easier to develop systems that can help patients suffering from these conditions,” said Giovanni Traverso, an MIT associate professor and gastroenterologist.<\/p>\n
Traverso, the senior author of the study published in Nature Biomedical Engineering, collaborated with lead author Christina Karavasili, a former MIT postdoc now at Aristotle University. Direct drug delivery is crucial for conditions like eosinophilic esophagitis, caused by food allergies, and Crohn’s disease, both leading to esophageal inflammation. Systemic treatments like infliximab, an immunosuppressant, pose infection risks, making targeted delivery advantageous.<\/p>\n
Oral drug passage through the esophagus is swift, and the tissue’s stratified squamous epithelium is highly impermeable. Injecting drugs is another option but is uncomfortable and requires a doctor’s visit. While some anti-inflammatory drugs are formulated to stay in the esophagus longer, they still struggle to penetrate the squamous layer.<\/p>\n
The researchers aimed to develop formulations with molecules that enhance esophageal cell permeability. They designed a screening system simulating the esophagus structure, allowing drug formulation testing for tissue permeability. This system identified effective excipients, notably a combination of bile salts, sodium chenodeoxycholate, and sodium cholate.<\/p>\n
These bile salts work together to loosen cell-cell junctions that block drug entry. The researchers combined them with a polysaccharide-derived hydrogel, which coats the esophageal lining. “The hydrogel helps the formulation remain on the esophageal surface for longer, while the bile salts help increase transport across the tissue,” Karavasili explained.<\/p>\n
Animal tests showed that this formulation could effectively deliver infliximab to the esophagus, with cell-cell junctions reverting to normal within three days. This method may reduce systemic side effects from infliximab. “We were interested in delivering anti-TNFs as a model drug, but also to help people who suffer from conditions like Crohn\u2019s disease to have options that could be delivered to the site,” Traverso stated.<\/p>\n
The team is refining the formulation for potential human trials, ensuring the gel adheres sufficiently to deliver drugs without causing discomfort. They are also exploring this technique for delivering other drugs. “This is a platform to enable the development of drug-delivery systems for the esophagus, which hasn\u2019t been possible before because the tools haven\u2019t existed,” Traverso noted.<\/p>\n