The end of the shot? Taking insulin in a pill

Researchers have succeeded in developing an oral (by mouth) method that could dramatically change the way diabetics monitor their blood sugar levels

[Translation by Dr. Nachmani Moshe]

Given the choice of swallowing a pill or injecting yourself with a substance through a needle, most of us will choose to manage our chronic medical condition by swallowing a pill. However, for millions of people dealing with type 1 diabetes (juvenile diabetes), the painful prick of a needle once or twice a day is the only option for injecting the insulin their body is unable to produce on its own. Now, researchers at Harvard University's School of Engineering and Applied Sciences have succeeded in developing an oral (oral) intake method that could dramatically change the way diabetics monitor their blood sugar levels. Not only does oral insulin promise to improve the quality of life of the forty million people with type 1 diabetes worldwide, but it may also alleviate the side effects of this life-threatening disease that result from patients not being able to inject themselves with the medicine they need. The research has long been published in the scientific journal Proceedings of the National Academy of Sciences.

Insulin treatment, in which the insulin is injected just under the skin or delivered via an insulin pump, maintains normal glucose levels in most diabetics. "However, the level of compliance of many of the patients to this method is low due to the pain, the anxiety of needles and the disruption to routine life involved in such treatment", says the main author of the article Professor Samir Mitragotri. "The consequences of poor glycemic control can lead to many health complications."

Finding a way to take insulin orally involved countless difficulties and challenges - insulin, which is a protein, does not function properly when it reaches the acidic environment of the stomach and is not well absorbed in the intestine. The key to the new approach lies in transferring the insulin in an ionic liquid consisting of choline and geranic acid, which is then inserted into a capsule with an acid-resistant coating. The composition itself is biocompatible, simple to manufacture and can be stored for up to two months at room temperature without disintegrating, a longer period than some of the commercial insulin syringes currently available on the market. "Once it enters the digestive system, insulin must navigate its way through a challenging obstacle course before it can effectively reach the bloodstream," said the lead researcher. By encapsulating the insulin-ionic liquid composition in a coating resistant to intestinal acid, the research team overcame the first obstacle - resistance to breakdown by stomach acids in the intestines. This polymeric coating dissolves only when it reaches a more alkaline environment in the small intestine, where the ionic liquid carrying the insulin is released and works its way into the bloodstream. "When a protein molecule, such as insulin, enters the intestine, there are many enzymes whose job it is to break down the proteins into their basic building blocks - amino acids. On the other hand, our insulin, which is in an ionic liquid, remains stable there." The composition of choline-granic acid was also found to be effective in overcoming two last obstacles - the mucous inner coating layer in the intestine and the intestinal walls through which large drug molecules such as insulin do not pass easily.

Other researchers have tried different measures in order to overcome these obstacles - by refolding the insulin molecule, coating the insulin with protective polymers, adding additives aimed at preventing the enzymatic discharge and adding substances designed to increase absorption. However, there is currently no product on the medical market that allows taking insulin orally.
"The development of ways to deliver protein and peptide drugs, for example insulin, orally, instead of by injection, was the holy grail in the field of drug development," said another of the researchers. He adds and says: "This study demonstrates amazing results that indicate that oral insulin in combination with an ionic liquid works with an efficiency similar to that of taking insulin by injection." The implications of this research in the field of medicine may be great, if the findings can be translated into pills that allow the safe and efficient transfer of insulin and other peptide drugs to humans."

Oral insulin more closely mimics the way the pancreas of healthy people produces and delivers insulin to the liver, where eighty percent of it is removed, and the rest enters the bloodstream. The innovative method could also alleviate the negative side effects resulting from long-term insulin injections. The researchers add and note that insulin carried by an ionic liquid can be produced in a one-step process that could easily be adapted to inexpensive commercial production, a fact that would make the cost of producing the oral formulation commercially acceptable.

In the next step, the researchers plan to conduct additional experiments on animals and also examine toxicological effects and compatibility with biological systems. The researchers believe that if these experiments are defined as a success, obtaining final approval for conducting experiments on humans will be easy in light of the fact that the main components of the ionic liquids - choline and granitic acid - are already defined as safe substances for human use; The American Food and Drug Administration has established a recommended daily dose for the consumption of choline, which is a vitamin-like nutrient, and granitic acid, a substance found naturally in cardamom (cardamom) and lemongrass, commonly used as a food additive. If further research progresses as expected, the new method could also be used for the oral intake of other proteins.

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