It is estimated that 422 million people worldwide have diabetes, and approximately 75 million inject themselves with insulin several times each day or have a permanently attached pump to keep their glucose levels within a healthy range and keep them alive.
If ingested, insulin is broken down so needs to be injected to be effective. Injectable insulin also needs to be kept cold, making it difficult to manage in hot or less developed countries or when travelling. The other drawback of injectable insulin is that it has the risk of causing glucose levels to crash leading to life-threatening hypoglycaemia (low blood sugar).
A team of researchers from The University of Sydney led by Dr Nicholas Hunt, Prof. Victoria Cogger, and Prof. David Le Couteur AO along with a Norwegian collaborator, have developed a way to protect insulin so it is no longer broken down in the gut.
They attached the insulin to quantum dots made of silver sulfide and then coated them with a shell that protects the insulin from the digestive processes, allowing it to accumulate in the liver. An enzyme in the liver, whose levels fluctuate in response to glucose levels, breaks down the coating releasing the insulin in the liver when glucose levels are high. As glucose levels fall, so do those of the enzyme, reducing the amount of insulin released from the nanoparticles. The team showed that this responsiveness to glucose levels appears to eliminate the occurrence of life-threatening hypoglycaemia.
Transmission electron microscopy at our University of Sydney facility was used to confirm the structure of the quantum dots and the assembled nanoparticles.
Phase 1A clinical trials will begin in March 2025 to test the product’s safety, with Phase 1B trials following in August to test its effect in patients with type 1 diabetes.
“The ability to validate that individual nanoparticles were of a uniform size and shape using microscopy was critical for publications, but even more for chemistry manufacturing and control processes that enable manufacturing for clinical trials” – Dr Nicholas Hunt
Research and development version of the oral insulin capsule. Credit: USyd / Stefanie Zingsheim
Transmission electron microscope images. Left: showing the structure of the insulin encapsulated nanoparticles, including the quantum dot (dark). Right: Crystalline structure
of the quantum dots.
This oral insulin opens a path to safer, temperature-stable, and needle-free treatment for diabetes sufferers worldwide. The researchers are now commercialising their formulation through Sydney-based spin-out Endo Axiom, tapping into the $30 billion global insulin market.
N. Hunt et al., Nature Nanotechnology 2024
DOI: 10.1038/s41565-023-01565-2
Dr Nicholas Hunt and Professor Victoria Cogger. Credit: The University of Sydney/Stefanie Zingsheim
March 10, 2025
