Health and Medicine Technology

An Insulin Release System That is Both Controllable and Sustained


The World Health Organization estimated in 2016 that the rate of obesity has increased and that 422 million people had diabetes. Over the past three decades, the occurrence of diabetes has grown internationally. The best treatment for diabetes, apart from exercise and proper diet, is the delivery of insulin into the body to manage blood glucose levels. This delivery has to be both controllable and sustainable over time.

A research group from Kumamoto University in Japan have been working toward the development of a better insulin delivery system. They have been experimenting with polyethylene glycol (PEG) modification (PEGylation) of protein drugs through a host-guest interaction between cyclodextrin (CyD) and adamantine. The objective of the research is to improve the stability and lifetime of insulin. The team have dubbed the results of their work “SPRA technology”.

Another previous development of the team allows for better control of insulin release and they are currently focusing on merging the SPRA technology with that. Their aim in combining the two technologies is to develop an insulin release system that is both controllable and sustained.

Image showing oncept for a sustained and controllable insulin release system by SPRA-PPRX technology. (Image credit: Dr. Hidetoshi Arima)
Image showing concept for a sustained and controllable insulin release system by SPRA-PPRX technology. (Image credit: Dr. Hidetoshi Arima)

The researchers developed four types of SPRA-insulin/CyD PPRXs:

  1. Multi SPRA-insulin/alpha-CyD.
  2. Mono SPRA-insulin/gamma-CyD.
  3. Multi SPRA-insulin/gamma-CyD PPRX.
  4. Mono SPRA-insulin/alpha-CyD.

This was achieved by using alpha- or gamma-cylodextrin (CyD) and mono- or multi-SPRA insulin solutions.

Gamma-CyD were found to form PPRXs with two PEG molecules of SPRA insulin, whereas Alpha-CyDs formed them with a single molecule.

The team expects that by using different concentrations of CyDs, it will allow them to control insulin release through the PEG and CyD equilibrium reaction, while multi SPRA-insulin will remain in the blood supply for a long time.

The insulin type with the highest CyD safety profile’s (multi/gamma) hypoglycemic effects was then evaluated in vivo. The team tested two gamma-CyD concentrations (232 mg/ml and 116 mg/ml) of multi SPRA-Insulin/gamma-CyD PPRX against a control of multi SPRA-insulin.

Dr. Hidetoshi Arima who led the study commented that 232 mg/ml gamma-CyD PPRX delivered a blood glucose reduction time that was longer than both the 116 mg/ml PPRX and the control. This is important as it shows that both controlled and sustained insulin release can be realized. Both are required for the treatment of diabetes. Arima added that the insulin injections did not change the safety analysis of blood chemistry of blood urea nitrogen, creatinine, alanine aminotransferase, or aspartate aminotransferase. The new SPRA-PPRX injections seem to be a reliable and safe insulin release system.

One limitation of this study is that the experiments were performed on only 3 rats per group. It was also unclear whether a diabetic animal model was used in the experiments or not.

The researchers plan to combine other forms of insulin with gamma-CyD PPRX in future work, hoping to improve diabetes treatment further.

The full study was published in the journal Carbohydrate Polymers.