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, according to theory, 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.
“The insulin molecules themselves are fine, so we wanted to develop a ‘magic fairy dust’ that you add into a vial that would help to fix the stability problem,” said Eric Appel, assistant professor of materials science and engineering at Stanford. “People often focus on the therapeutic agents in a drug formulation but, by focusing only on the performance additives—parts that were once referred to as ‘inactive ingredients’ – we can achieve really big advancements in the overall efficacy of the drug.”
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. (By comparison, commercial fast-acting insulin stays stable for six to ten hours under the same conditions.) The researchers then confirmed the ultrafast action of their formulation in diabetic pigs. Their results were published July 1 in Science Translational Medicine. Now, the researchers are conducting additional tests in hopes of qualifying for clinical trials in humans.
One step back, two steps forward
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.
“We 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,” said Joseph Mann, a graduate student in the Appel lab and co-lead author of the paper. Crucially, the polymer can do this without interacting with the insulin molecules themselves, allowing the drug to take effect unimpeded.
JULY 1, 2020