Patients suffering from Type 1 diabetes need to measure their blood glucose levels twice daily and perform an under-the-skin injection to deliver insulin to keep their glucose levels under control. The failure to perform the tests and administer insulin regularly can lead to serious health complications, yet even so, many diabetes patients fail to administer insulin when it is needed by their bodies.
Part of the reason is the pain caused by the needle and taking insulin in this way interferes with daily activities. For patients with a phobia of needles the problem is even worse. Unfortunately, injecting insulin is the only effective method of introducing the hormone. While it would be much easier for patients to take an oral insulin pill when needed, insulin does not survive the acidic environment of the stomach and absorption is poor via the intestine.
Attempts have naturally been made to develop an oral insulin pill for the 40 million worldwide patients suffering from the disease, but little progress has been made. However, scientists at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have made significant progress in this area and have developed an oral insulin pill that is capable of surviving passage through the stomach and is not broken down by enzymes in the intestine.
The researchers added insulin to an ionic liquid consisting of choline and geranic acid, which was encased in an acid-resistant capsule. The capsule is biocompatible, is not broken down by gastric acid, but when the pill passes into the alkaline environment of the small intestine it begins to break down. There are enzymes in the intestine whose function is to break down proteins into easily absorbable amino acids; however, the researchers report that the ionic liquid keeps the insulin stable, helps it pass through the mucus coating the intestine wall, and penetrate the cell junctions of the intestine wall.
The research suggests that this new insulin delivery method could be just as effective as conventional injections, without the pain and the inconvenience for patients. Further, this method of delivery could be used for other proteins and peptides.
The researchers said the ionic-liquid-insulin can be created in a single step process, the capsules are easy to manufacture, and the oral insulin pills can be stored for up to two months – longer than some injectable insulin products. Further, gaining approval for this oral insulin pill from regulatory bodies such as the FDA is likely to be relatively straightforward. The the two compounds in the ionic liquid are already deemed safe for use. Choline is an essential nutrient, for which there is a current RDA, and geranic acid is a naturally occurring compound that is present in several foodstuffs and is already used as a food additive.
Samir Mitragotri, Hiller Professor of Bioengineering and Hansjorg Wyss Professor of Biologically Inspired Engineering at SEAS, and senior author of the paper, said manufacturing the oral insulin pills is easily scalable. However, first, further animal tests are required, and long-term toxicological and bioavailability studies need to be conducted.
The research is detailed in the paper – Ionic liquids for oral insulin delivery – which was recently published in the journal, Proceedings of the National Academy of Sciences, 2018; 201722338 DOI