Though synthetic insulin and blood glucose meters have been available for decades, diabetics continue experiencing abnormal sugar levels because it’s almost impossible to continuously monitor glucose and inject insulin in real-time with sufficient precision. Wearable glucose meters and insulin pumps are currently being investigated to work together as an “artificial pancreas,” but there seems to be a limit to how fast changes in blood sugar can be detected and proper insulin dosages delivered.

Now a collaboration between North Carolina State University, University of North Carolina at Chapel Hill, MIT, and Boston Children’s Hospital has developed and is analyzing a new material that can encapsulate insulin and release it as needed into the blood stream. Made of chitosan, a substance often found in the shells of crustaceans, with a bit of chemical trickery the material expands in the presence of high concentrations of glucose, allowing insulin to flow out and immediately counteract the sugar rush. As glucose levels return to normal, the sponge-like material contracts and stops the flow of insulin. This technique essentially replicates the functionality of β-cells within the pancreas, but further research needs to confirm the safety and efficacy of this technology within diabetic patients. Moreover, the technique allows for other therapeutic compounds to be delivered in response to certain biomarkers, potentially allowing for more targeted treatment of cancer and other diseases.

In this image, the “smart sponges” are exposed to high glucose levels and are swelling to release insulin. Image: Zhen Gu

More details from North Carolina State:

The researchers created a spherical, sponge-like matrix out of chitosan, a material found in shrimp and crab shells. Scattered throughout this matrix are smaller nanocapsules made of a porous polymer that contain glucose oxidase or catalase enzymes. The sponge-like matrix surrounds a reservoir that contains insulin. The entire matrix sphere is approximately 250 micrometers in diameter and can be injected into a patient.

As the insulin is released, the body’s glucose levels begin to drop. This causes the chitosan to lose its positive charge, and the strands begin to come back together. This shrinks the size of the pores in the sponge, trapping the remaining insulin.When a diabetic patient’s blood sugar rises, the glucose triggers a reaction that causes the nanocapsules’ enzymes to release hydrogen ions. Those ions bind to the molecular strands of the chitosan sponge, giving them a positive charge. The positively charged chitosan strands then push away from each other, creating larger gaps in the sponge’s pores that allow the insulin to escape into the bloodstream. In type 1 and advanced type 2 diabetes, the body needs injections of insulin, a hormone that transports glucose – or blood sugar – from the bloodstream into the body’s cells.

While this work created hydrogen ions by using enzymes that are responsive to glucose, the technique could be simplified to target cancers by eliminating the enzymes altogether. Tumors are acidic environments that have high concentrations of hydrogen ions. If the sponge reservoir were filled with anticancer drugs, the drugs would be released when the chitosan came into contact with the hydrogen ions in tumor tissues or cancer cells.

Study in ACS Nano: Glucose-Responsive Microgels Integrated with Enzyme Nanocapsules for Closed-Loop Insulin Delivery

NC State: Injectable ‘Smart Sponge’ Holds Promise for Controlled Drug Delivery