MIT researchers tap liquid dopamine for easier drug delivery in the gut

Taking inspiration from the sticky substance mussels use to cling to rocks, researchers at Massachusetts Institute of Technology have developed a drinkable coating for the lower intestine that could deliver treatments for a range of conditions, from lactose intolerance to diabetes—and boost drugs' staying power in the body, too. 

The small intestine is a major player when it comes to drug absorption, but if it processes medication too quickly, patients may need multiple doses a day. Researchers have previously tackled the problem by developing pH-dependent drug capsules and other synthetic coatings, but overall, "GI tract targeting is challenging," lead study author Junwei Li said via email. 

The team's solution? Using a once-daily, liquid dopamine formulation to create a gastrointestinal synthetic epithelial lining, or GSEL. Once the liquid dose hits the upper region of the small intestine, it forms a super-sticky coating that lasts for around 24 hours, animal research has shown. The synthetic lining can carry drugs to the site and keep them there for slow, steady absorption.

The team first set out to develop an easy-to-swallow, liquid alternative to pH-dependent capsules, which would be useful for treating children and others who might have trouble swallowing them. 

"We started to think about whether we could develop liquid formulations that could form a synthetic epithelial lining that could then be used for drug delivery, making it easier for the patient to receive the medication by providing drugs in extended release formats," Li said. 

The scientists discovered that an enzyme called catalase, abundant in the upper small intestine, could help assemble molecule building blocks—in this case dopamine—to form a polymer with "muco-adhesion properties," Li said. The resulting polymer, polydopamine—similar to the adhesive that helps mussels cling to rocks—sticks to the surface of the GI tract "very strongly," Li added. 

To ensure that the GSEL works quickly, the researchers paired their liquid dopamine solution with a small amount of hydrogen peroxide. Once the solution hits the small intestine, catalase breaks down the hydrogen peroxide, creating oxygen bubbles that help the polymer film form in a matter of minutes, the team said. 

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To test its drug delivery, the team paired it with praziquantel, a drug used to treat parasitic worm infections, for a trial in pigs. The film increased the half-life of praziquantel tenfold and cut dosing to once each day instead of three times, Li said. 

Starting with praziquantel powder, the team made minor additions to the surface of drug particles to meld them with the GSEL solution, Li said. Eventually, the team hopes a wide range of drugs could be formulated to work with the synthetic lining. 

Meanwhile, in another pig trial, the team tested their platform's ability to deliver digestive enzymes. Loaded up with the enzyme lactase, the GSEL was able to break down the milk sugar lactose 20 times better than usual in the intestine, Li said—a potential boon for people who are lactose-intolerant or suffer from other digestive health issues. 

Plus, the researchers were able to make the coating impenetrable to glucose by embedding nanoparticles called crosslinkers. The team thinks GSEL's ability to form a barrier in the GI tract could help patients managing diabetes, obesity or other metabolic disorders caused by excess glucose levels.

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The synthetic coating lasts for around a day, at which point the film is shed along with cells that make up the intestinal lining. The pig research found no difference in nutrient absorption capacity after 24 hours, between animals that had received the synthetic coating and those that had not. Early safety trials in rats showed the coating did not lead to any side effects, and a large animal study found no increased levels of dopamine in the tissue or bloodstream. 

Next up for the MIT team? Another round of animal studies to confirm their platform's safety and tolerability, Li said. The team has a "significant set of applications" for those safety trials in process, Li said, adding that the team hopes to enter human trials in the next three to five years.