Polymer Boosts Insulin Speed, Stability

(angelsalamag054, Pixabay)

2 July 2020. Researchers discovered a polymer compound added to insulin that in tests with pigs cuts insulin’s acting time in half and more than doubles its usable life. A bio-materials science team from Stanford University in California describes its faster-acting insulin in yesterday’s issue of the journal Science Translational Medicine (paid subscription required).

People with type 1 diabetes require continuous blood glucose monitoring and replenishment of insulin, particularly around meal times. Type 1 diabetes is an autoimmune disorder where islet cells in the pancreas do not produce insulin. The disease is diagnosed primarily in children or young adults, where the immune system is tricked into attacking healthy cells and tissue as if they were foreign invaders, in this case, insulin-producing islet cells. Five to 10 percent of people with diabetes have the type 1 form.

Advances in technology make it easier to monitor blood glucose levels and replenish insulin, but most fast-acting insulin formulations, say the authors, can take 20 to 30 minutes to begin acting. These higher-speed formulations use a mix of insulin molecules, with more of the fastest-acting molecules called monomers in the mix. Monomers, however, are unstable, breaking down more quickly than the slower insulin molecules that last longer. The problem undertaken by the researchers is to find a way to use faster insulin monomers, but keep them stable and thus more usable for longer periods.

The team from the lab of Stanford materials science and engineering professor Eric Appel are looking for a safe additive for insulin monomers to extend their usable life. “People often focus on the therapeutic agents in a drug formulation,” says Appel in a university statement, “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.”

The researchers led by doctoral students and co-first authors Joseph Mann and Caitlin Maikawa evaluated some 1,500 polymer additive candidates, first with statistical simulations, then robotic testing with colleagues in Australia. The team looked particularly for polymers to prevent the aggregation of monomers that deactivate their potency. Their search resulted in identifying an acrylamide compound, a type of widely-used natural polymer, but without the liver or kidney toxicities found in some variations.

The Stanford team assessed its acrylamide as an additive to Humalog, a commercial fast-acting insulin injected under the skin. In tests with insulin-deficient pigs, animals with organs about the same size and functions as humans, the enhanced insulin achieves its peak activity in about nine minutes, compared to 25 minutes for regular Humalog. In addition, the enhanced Humalog remains stable under stressed aging conditions — continuous agitation of the insulin at normal body temperature of 37 degrees C — for 25 hours, compared to about 10 hours for off-the-shelf Humalog.

“It’s really unprecedented,” notes Appel. “This has been a major target for many big pharmaceutical companies for decades.” Stanford University filed a provisional patent for the enhanced insulin technology, with Appel, Mann, and Maikawa listed as inventors. The researchers also plan to submit a request to the Food and Drug Administration to begin clinical trials of the enhanced insulin.

More from Science & Enterprise:

• Vaccine Blocks Suspected Type 1 Diabetes Infections
• Engineered Antibody Delays Type 1 Diabetes Onset
• Small Business Grant Funds Diabetes Rescue Device
• Closed-Loop System Boosts Diabetes Glucose Control
• Univ. Developing Implanted Islet Cell Bags for Diabetes

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