Lipid nanoparticles that are charge-switchable and respond to glucose for delivering insulin

People with type 1 diabetes have a constant risk of developing either hyperglycemia or hypoglycemia. Finely controlled insulin secretion can help improve the regulation of blood sugar levels. reported in the journal Angwandt KimiNow, a research team has presented a new insulin formulation that can be triggered by glucose: Lipid nanoparticle transporters release more or less insulin depending on the level of glucose in the blood.

Plasma insulin levels are mainly regulated by beta cells in the pancreas and reflect fluctuations in the level of glucose in the blood. Patients with type 1 diabetes can produce very little or no insulin and require several daily injections of rapid-acting insulin as well as one or two injections of long-acting insulin to keep blood sugar at a normal level.

Instead, they wear an insulin pump that provides a continuous infusion. Insulin formulations cannot react to changes in the level of glucose in the blood and therefore do not allow for precise regulation of blood sugar. If insulin is overdosed, a meal is missed, or too few carbohydrates are eaten before strenuous physical activity, there is an increased risk of severe, life-threatening hypoglycemia.

Glucose-responsive insulin formulations, which mimic the function of beta cells, can improve insulin therapy. Different methods with insulin “carriers” made of polymers with an incorporated glucose oxidase as a glucose detector suffer from two problems: the polymer transporters are not of uniform molecular weight and the glucose oxidase is toxic if released into the body.

A Chinese team led by Jinqiang Wang and Zhen Gu at Zhejiang University, Zhejiang Cancer Hospital and the University of Hong Kong chose a different approach based on biocompatible lipid nanoparticles used as lipid carriers with uniform chemical structures. Lipid nanoparticles are already widely used as drug carriers.

A section of lipids has been modified so that the surfaces of the self-assembled nanoparticles carry many positive charges. Negatively charged insulin particles are electrostatically attached to the nanoparticles and slowly released when the blood glucose level is normal. If the blood sugar level is high, some of the lipids in the nanoparticles form chemical bonds with the glucose, which reduces the positive charge on the surface and greatly accelerates insulin release.

In diabetic mice treated with the new insulin formulation, it was possible to maintain a normal blood sugar level for six hours. After the glucose injection, the blood sugar in the diabetic mice dropped to a normal level just as quickly as the healthy mice.

In the future, combining a glucose-responsive insulin formulation with a dispenser controlled by a wearable electronic glucose detector could significantly improve blood glucose regulation in diabetic patients.