The most effective way for people with diabetes to deliver insulin is also incredibly intrusive. Millions around the world must inject the crucial hormone underneath their skin several times a day to keep their glucose levels in balance. For years, scientists have looked for an easier, cheaper, more convenient, and less wasteful alternative to insulin pumps and pens. While potential oral treatments are making headway, there are still several hurdles to overcome. A new approach seems to have come up with a solution to at least some of them, so far proving effective in pre- clinical trials on rats. Shortly after insulin was discovered in 1922, researchers tried and failed to make a swallowable supplement with lasting effects. Injecting insulin into subcutaneous tissues allows the protein to slowly absorb into the body and be carried to the liver to perform its job. When delivered via the mouth, any molecules that don't clump together are rapidly broken down by protein-digesting enzymes. To get enough medicine past these enzymes and into the liver, researchers have found they can coat the insulin in protective materials. It's an effective approach that works best when the insulin is in nanoparticle form. One example, Oramed, has so far proven safe and effective enough to make it through to phase three clinical trials. It's a method full of potential, but those nanoparticles aren't as stable as chemists might like. Freeze-drying them before storage helps, but the practice requires a preservative that bulks up the pills and reduces the efficiency of the insulin nanoparticles. Unlike many other oral therapies currently being tested, a new one being studied by scientists in Canada is not made by freeze-drying the hormone with a cryoprotectant. Instead, the researchers 'spray-dried' the insulin in an evaporative chamber instead of a freezer. By removing the cryoprotectant from the mix, the insulin particles can be made even smaller, allowing for faster drug release into the body. "The small particles provided a large surface area so that most of the drugs associated would be at or close to the particle surface, resulting in fast drug release," the researchers write in a new paper. The new pill is made to dissolve in the mouth, but it still needs to be protected from enzymes in saliva. To do that, the team encapsulated the medicine in a fibrous sugar called chitosan that reduces the fat and cholesterol the body absorbs from both food and drugs. Compared to other forms of oral insulin made via freeze-drying, the researchers say this new method showed a faster relief profile in rats. Instead of taking two to four hours to hit before rapidly breaking down, the new oral pill acts quickly and for a long period. "Similar to the rapid-acting insulin injection, our oral delivery tablet absorbs after half an hour and can last for about two to four hours long," says particle engineer Alberto Baldelli from the University of British Columbia. In fact, the latest version of their drug supposedly shows the same benefits among rodents as injected insulin. The authors say almost 100 percent of their medicine goes straight to the rats' livers. Those findings are not yet published, but if the authors are right, their research is far from over. Human trials are still a ways away, but these initial results suggest there may be other ways to make oral insulin a reality in the future. "These exciting results show that we are on the right track in developing an insulin formulation that will no longer need to be injected before every meal, improving the quality of life, as well as mental health, of more than nine million Type 1 diabetics around the world," says chemical engineer Anubhav Pratap-Singh from the University of British Columbia. Source
