Type 2 diabetes is a leading cause of blindness, amputations, renal failure and poor cardiovascular outcomes, and is characterized by high levels of blood glucose, which must cross the barrier of the small intestine to enter the bloodstream. Thus, modulating nutrient exposure to the small intestine would offer a therapeutic strategy for the treatment of type 2 diabetes. “Bariatric surgery, bypassing the stomach and part of the intestine from the food stream, has shown very promising results, but the high body mass index requirements to qualify and risks of surgery along with permanent changes to gastrointestinal anatomy deter many patients from surgery,” explains Karp. “Therefore, there is an urgent need for a safe, non-invasive and effective treatment for a wider diabetic patient population.” However, directing therapeutic agents to the small intestine through oral drug delivery is challenging and usually requires systemic administration. Moreover, the highly acidic and proteolytic environment of the stomach can affect drug activity.
The US Food and Drug Administration (FDA)-approved drug, sucralfate, contains anioinic sucrose octasulfate and a cationic polyaluminium complex, which, when exposed to acidic pH in the stomach, form a sticky paste. Karp and colleagues engineered this material into a coacervate assembled by pH-independent electrostatic interactions, making it reversibly (de)hydratable and attach to both healthy and diseased intestinal mucosa. Therefore, the material can be ingested as an oral drug in the form of a powder and, once hydrated, establishes a continuous coating along the inner wall of the intestine, providing a barrier to the uptake of nutrients. By adjusting the viscosity of the material, the location, extent and durability of the coating can be tailored. “We envisioned a pill that a patient can take before a meal that transiently coats the gut to replicate the effects of bariatric surgery,” says Tavakkoli.
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