The prevalence of diabetes has grown around the world over the past
three decades. In 2016, the World Health Organization estimated that 422
million people had the disease as the rate of obesity also increased.
Aside from proper diet and exercise, the best treatment for diabetes is
the delivery of insulin into the body that is both controllable and
sustainable over time to manage blood glucose levels.
‘Research teams have been experimenting with polyethylene glycol (PEG) modification (PEGylation) of protein drugs to improve the stability and lifetime of insulin.’
Working toward the
development of a better insulin delivery system, a research group from
Kumamoto University in Japan has been experimenting with polyethylene
glycol (PEG) modification (PEGylation) of protein drugs through a
host-guest interaction between cyclodextrin (CyD) and adamantane to
improve the stability and lifetime of insulin, calling the results of
their work "SPRA technology".
Their current research focuses on
combining SPRA technology with another development of their own that
allows for better control of insulin release, "polypseudorotaxane (PPRX)
technology". Their goal in combining the two technologies was to
develop a sustained and controllable insulin release system.
Using mono- or multi-SPRA-insulin solutions and alpha- or
gamma-cylodextrin (CyD), the researchers developed four types of
SPRA-insulin/CyD PPRXs, mono-SPRA-insulin/alpha-CyD,
mono-SPRA-insulin/gamma-CyD, multi-SPRA-insulin/alpha-CyD, and
multi-SPRA-insulin/gamma-CyD PPRX. Alpha-CyDs were found to form PPRXs
with a single PEG molecule of SPRA-insulin, whereas gamma-CyD formed
them with two molecules. The multi-SPRA-insulin was expected to remain
in the blood supply for a relatively long period of time, and the use of
different concentrations of CyDs allowed researchers to control insulin
release through the CyD and PEG equilibrium reaction.
The hypoglycemic effects of the insulin type with the highest CyD
safety profile (multi/gamma) was then assessed in vivo. Two gamma-CyD
concentrations, 116 mg/ml and 232 mg/ml, of multi-SPRA-Insulin/gamma-CyD
PPRX were tested against a control of multi-SPRA-insulin.
that 232 mg/ml gamma-CyD PPRX provided for a longer blood glucose
reduction time than the 116 mg/ml PPRX and the control. This is quite
important since it shows that both sustained and controlled insulin
release can be achieved, which is necessary for the treatment of
diabetes," said lead researcher Dr. Hidetoshi Arima. "Furthermore, a
blood chemistry safety analysis of creatinine, blood urea nitrogen,
aspartate aminotransferase, and alanine aminotransferase were found to
be unchanged by the insulin injections. Our SPRA-PPRX injections appear
to be a safe and reliable insulin release system."
A limitation of this study is the low number of experimental
subjects, only 3 rats per group. Also, it was unclear whether or not a
diabetic animal model was used in the experiments.
In future work, the researchers plan to combine other forms of
insulin with gamma-CyD PPRX with the hope of further improving diabetes
treatment. The current findings be found online in the journal Carbohydrate Polymers