Researchers at Stanford University are developing a new insulin formulation that begins to take effect almost immediately upon injection, potentially working four times as fast as current commercial fast-acting insulin formulations.
The researchers focused on so-called monomeric insulin, which has a molecular structure that should allow it to act faster than other forms of insulin. The catch is that monomeric insulin is too unstable for practical use. So, in order to realize the ultrafast potential of this insulin, the researchers relied on some materials science magic.
After screening and testing a large library of additive polymers, the researchers found one that could stabilize monomeric insulin for more than 24 hours in stressed conditions. The researchers then confirmed the ultrafast action of their formulation in diabetic pigs. Their results were published in the journal Science Translational Medicine. Now, the researchers are conducting additional tests in hopes of qualifying for clinical trials in humans.
Current commercial formulations of insulin contain a mix of three forms: monomers, dimers and hexamers. Scientists have assumed monomers would be the most readily useful in the body but, within 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 because they first have to break down into monomers to become active. This is where the “magic fairy dust” – a custom polymer that is attracted to the air/water interface – comes in.
The Stanford researchers focused on polymers that would preferentially go to that interface and act as a barrier between any of the insulin molecules trying to gather there.
Crucially, the polymer can do this without interacting with the insulin molecules themselves, allowing the drug to take effect unimpeded.
Finding just the right polymer with the desired properties was a long process that involved a three-week trip to Australia, where a fast-moving robot created approximately 1500 preliminary candidates. This was followed by processing and testing individually by hand at Stanford to identify polymers that successfully exhibited the desired barrier behavior.
The researchers were able to evaluate their new monomeric insulin formulation in diabetic pigs – the most advanced non-human animal model – and found that their insulin reached 90 percent of its peak activity within five minutes after the insulin injection. For comparison, the commercial fast-acting insulin began showing significant activity only after 10 minutes. Furthermore, the monomeric insulin activity peaked at about 10 minutes while the commercial insulin required 25 minutes. In humans, this difference could translate to a four-fold decrease in the time insulin takes to reach peak activity.
The monomeric insulin also finished its action sooner. Both beginning and ending activity sooner makes it easier for people to use insulin in coordination with mealtime glucose levels to appropriately manage their blood sugar levels.
The researchers plan to apply to the Food and Drug Administration for approval to test their insulin formulation in clinical trials with human participants (although no trials are planned yet and they are not seeking participants at this time). They are also considering other uses for their polymer, given how significantly it increased stability in commercial insulin.
Because their insulin formulation activates so quickly – and, therefore, more like insulin in a person without diabetes – the researchers are excited by the possibility that it could aid the development of an artificial pancreas device that functions without the need for patient intervention at mealtimes.
News Source: Stanford
