Type 1 diabetics must constantly control their blood glucose with insulin. It’s a Goldilocks-type situation: administer too much insulin, and they risk low blood glucose (hypoglycemia), while too little can lead to high blood glucose (hyperglycemia). Researchers have developed a self-adjusting nanoparticle-based insulin formulation that may go some way towards improving blood glucose control.
Type 1 diabetes (T1D) is an autoimmune disease where the body’s immune system attacks the insulin-producing beta cells of the pancreas so that little or no insulin is produced. The exact cause of T1D is unknown but is thought to be due to genetics and some viruses.
Treatment of T1D requires taking fast-acting insulin, either by intermittent, manual injections or continuously via an insulin pump, and regularly monitoring blood glucose levels to avoid hypo- and hyperglycemia, both of which can have life-threatening consequences. Long-acting insulin might also be used to provide a slow, steady release of insulin.
The use of nanoparticles to deliver drug and gene therapy has had a tremendous impact on how diseases are treated. Now, a team of Chinese researchers has used a particular kind of nanoparticle to create a self-adjusting insulin release system.
Glucose-sensitive insulin-delivery systems using insulin ‘carriers’ made of polymers containing the enzyme glucose oxidase have gained popularity but can cause problems. The polymers are not of uniform molecular weight, and glucose oxidase can be toxic. Given these issues, the researchers turned to a different kind of carrier: biocompatible lipid nanoparticles.
Biocompatible lipid nanoparticles are already widely used as drug carriers. Moreover, they have a uniform chemical structure. For this study, the researchers modified a section of the nanoparticles’ surface so that it could carry many positive charges. The negatively charged insulin molecules bind electrostatically to the lipid nanoparticles.
Testing their insulin formulation on diabetic mice, the researchers found that when blood glucose levels were normal, insulin was released slowly. But if blood glucose was high, lipids in the nanoparticles formed chemical bonds with the glucose, reducing the positive charge on the nanoparticle’s surface and significantly accelerating insulin release.
After being injected with glucose, the blood glucose levels of the diabetic mice treated with the insulin formulation fell to a normal level at the same rate as the healthy mice and maintained a normal blood glucose level for six hours.
The researchers are hopeful that, in future, this kind of glucose-responsive insulin formulation can be incorporated into wearable electronics, significantly improving blood glucose control in type 1 diabetics.
The study was published in the journal Angewandte Chemie.
Source: Zhejiang University via Wiley Online Library
