Researchers at Stanford University are developing a new, fast-acting insulin that takes effect almost immediately after injection. The polymer is potentially four times faster than current commercial formulas. The team focused on something called monomeric insulin, which has a molecular structure. Theoretically, this should allow it to be absorbed into the blood more quickly. The catch, however, is that such...Insulin secretion to treat diabetesis too unstable for practical use. To realize the ultrafast potential of this product, researchers relied on some materials science methods.
Reformulate rapid-acting insulin
The insulin molecules themselves are fine, so the scientists wanted to develop a new type of formula that they put in a vial to address the stability problem. After screening and testing a large library of additive polymers, the researchers found one that could stabilize monomeric insulin for more than 24 hours under stressful conditions. In comparison, commercial rapid-acting insulin remains stable for six to ten hours under the same conditions. The researchers then confirmed the ultra-fast effect of their formulation in diabetic pigs. Now they are conducting additional testing to qualify for human clinical trials.
Current commercial formulas for rapid-acting insulin contain a mixture of monomers, dimers, and hexamers. Scientists have suggested that monomers are the most useful in the body. However, in vials, the insulin molecules are drawn to the surface of the liquid, where they aggregate and become inactive. Hexamers are more stable in the vial but take longer to work in the body. This is because they must first break down into monomers in order to become active. This is where the magic additive – a special polymer – comes into play. It is attracted to the air so that a water interface can be created. Finding the right polymer with the desired properties was a long process that included a three-week trip to Australia. There, a fast-moving robot created approximately 1,500 preliminary candidates.
The development process
Candidates were then individually hand processed and tested to identify polymers that successfully demonstrated the desired behavior. The first 100 candidates did not stabilize commercial insulin in tests, but the researchers continued. They found their magic polymer weeks before they were scheduled to conduct experiments on diabetic pigs. In commercial insulin, which typically remains stable for about 10 hours in accelerated aging tests, the polymer dramatically increased the duration of stability over a month. The next step was to check how the polymer affects the monomeric insulin, which self-aggregates in 1-2 hours. It was another welcome victory when researchers confirmed that their formula could remain stable for over 24 hours under stress.
The researchers were then able to determine that their fast-acting insulin reached 90 percent of its peak activity within five minutes of insulin injection. For comparison, the commercial product only showed significant activity after 10 minutes. In addition, the monomericInsulin activity peaksat about 10 minutes, while the commercial insulin took 25 minutes. In humans, this difference could result in a fourfold increase in the time to reach peak activity. The monomeric insulin also stopped working earlier. Both the start and end of activity make it easier for people to use insulin in coordination with glucose levels during meals to appropriately manage their blood sugar levels.
The researchers are planningof the studyto test their formula in clinical trials with human participants. They are also considering other uses for their polymer as it significantly increases stability in commercial insulin. So this works as quickly as insulin does in a person without diabetes. That's why researchers are excited about the possibility that it can support the development of an artificial pancreas that works at mealtimes without patient intervention.
