Titre : Protective liquid enables oral insulin delivery in rats
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Protective liquid enables oral insulin delivery in rats
July 17, 2018Protective liquid enables oral insulin delivery in rats
—by Sharon Reynolds
More than 30 million people in the United States live with diabetes, a disease in which the body has trouble managing and using blood glucose, the sugar that serves as the body’s fuel. Tens of millions more live with prediabetes, a condition where blood glucose levels are higher than normal, but not high enough to be considered diabetes. When blood sugar isn’t controlled for long periods of time, it can cause a range of health problems, including nerve damage and heart or kidney disease.
People with diabetes must actively monitor and control their blood sugar levels. Many need injections of insulin, a hormone that helps the body process glucose, several times a day to keep their blood sugar levels under control. But it can be difficult and painful to keep up with insulin injections. An oral form of insulin would drastically ease the difficulty of maintaining healthy blood sugar levels.
Insulin runs into many obstacles when taken by mouth. First, acid in the stomach can degrade it. Second, any insulin that reaches the small intestine from the stomach can be chopped up by the enzymes that help break down food. Finally, insulin needs to be absorbed into the bloodstream through the cells that line the small intestine.
A research team led by Dr. Samir Mitragotri of Harvard University has been exploring the uses of an ionic liquid called CAGE. Ionic liquids contain both positively and negatively charged molecules. CAGE is made from two non-toxic compounds, choline and geranate. In previous work, the team showed that CAGE could be used to deliver antibiotics and insulin through the skin of rats.
In their latest study, the team tested whether CAGE could protect insulin from degradation by the digestive system and help it through the intestinal lining. The research was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results were published in the Proceedings of the National Academy of Sciences on July 10, 2018.
The researchers first tested whether their insulin-CAGE solution was stable. The structure and function of insulin remained intact in CAGE for 2 months at room temperature and at least 4 months when refrigerated.
When injected directly into the small intestines of non-diabetic rats, the solution quickly lowered blood sugar levels by up to 65%. Insulin-CAGE delivered through the small intestine lasted longer in the bloodstream than insulin injected under the skin.
The researchers next packaged insulin-CAGE into enterically coated capsules. Enteric coatings are resistant to stomach acid but dissolve when they reach the small intestine. When given by mouth to rats, the capsules caused a slow and steady drop in blood sugar, by about half over 10 hours. This drop was smoother and longer lasting than that caused by injection. Samples taken from the intestinal walls after administration showed no damage caused by the insulin-CAGE solution.
“Once ingested, insulin must navigate a challenging obstacle course before it can effectively be absorbed into the bloodstream,” Mitragotri says. “Our approach is like a Swiss Army knife, where one pill has tools for addressing each of the obstacles that are encountered.”
The researchers are now planning studies with diabetic animals to gauge the long-term safety and effectiveness of oral insulin-CAGE. They hope to eventually test the approach in a human clinical trial.
Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the National Science Foundation; Harvard University; and the Natural Sciences and Engineering Research Council of Canada.
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