Investigators from Brigham and Women's Hospital and the Massachusetts Institute of Technology are working on an innovative way of sustainably delivering drugs and influencing nutrient absorption in the gut. The gastrointestinal synthetic epithelial lining (GSEL) system is designed to coat the small intestine, an organ that plays a key role in drug and nutrient absorption. The team has demonstrated the GSEL system's ability to adhere to segments of the gastrointestinal tract from pigs and humans, and, in porcine models, has reported potential applications for the system in treating a variety of conditions, ranging from lactose intolerance to diabetes and obesity to tropical diseases such as schistosomiasis. Results of the team's proof-of-concept studies are published in Science Translational Medicine.
"The small intestine is an amazing organ -- it's the main site of drug and nutrient absorption and digestion and plays an important role as a barrier. We recognized its potential: If we could specifically target this location, it would open up new avenues for drug delivery and nutritional modulation," said corresponding author C. Giovanni Traverso, MB, BChir, PhD, a gastroenterologist and biomedical engineer in the Division of Gastroenterology at the Brigham. "The system we've developed has the potential to treat and manage a variety of diseases."
"We found that enzymes in the digestive tract can help synthesize polymers in the small intestine," said first author Junwei Li, who will become a research fellow at the Brigham this fall. "We anticipate broad adoption of this in-situ biomaterial generation idea for various applications."
The GSEL system combines two nature-inspired innovations. The first takes advantage of a chemical reaction triggered by catalase, an enzyme that helps break down hydrogen peroxide into oxygen in the small intestine. The second is a mussel-inspired tissue adhesive, similar to what mollusks use to attach themselves to rocks. Using these two concepts, Traverso, Li and colleagues designed a synthetic gut lining that can target the small intestine. Their goal is to develop a capsule, pill or gel that could be ingested, but for now, the team has tested administering the GSEL system endoscopically -- that is, directly inserting it into the small intestine.
To test the lining's therapeutic potential, the team looked at pig models for testing lactose intolerance, glucose absorption and the delivery of praziquantel, a drug for treating schistosomiasis. The team found evidence that the lining could deliver the drug in a sustained way, potentially reducing treatment to a once-a-day dose instead of three time a day. It also improved lactose digestion and regulated glucose absorption, indicating its potential for treating type 2 diabetes and preventing obesity.
In order to move from pig models into human trials, several hurdles remain, including further developing the GSEL system into an ingestible form. For now, Traverso, Li and colleagues are focused on continuing to evaluate safety in preclinical studies.
"For our studies, safety is a key focus of our work," said Traverso. "There are indications that this system can help patients suffering from many diseases, but before we can translate this technology for humans, we need to fully validate its safety and the effects of chronic use."
This work was supported by the Bill and Melinda Gates Foundation grants (OPP1179091), the NIH (EB000244) and funds from the Department of Mechanical Engineering, MIT. Traverso and co-authors declare submission of provisional patent applications describing the materials and applications of GSELs described here. Complete details of all relationships for profit and not for profit for Traverso can be found at the following link: http://www.
Paper cited: Li J et al. "Gastrointestinal synthetic epithelial linings" Science Translational Medicine DOI: 10.1126/scitranslmed.abc0441