An extended insulin-release system comprising an injectable gel of nanoparticles may one day help patients with type 1 diabetes manage their condition without having constantly to test their blood-sugar and inject themselves with insulin.
Designed at Massachusetts Institute of Technology (MIT) in the US, once in the body, the nanoparticles sense blood glucose concentration and automatically secrete the appropriate amount of insulin to keep it at the right level.
Daniel Anderson, an associate professor of chemical engineering, leads the lab that designed the nanogel. He says in a statement:
“Insulin really works, but the problem is people don’t always get the right amount of it. With this system of extended release, the amount of drug secreted is proportional to the needs of the body.”
Anderson, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and his colleagues, write about the nanogel and how they tested it in mice, in a paper published online in the journal ACS Nano on 2 May.
The researchers hope that their system or something like it will someday improve the quality of life of people with type 1 diabetes so they don’t have to keep pricking their fingers to check their blood sugar levels and constantly inject themselves with insulin to break down any excess sugar.
In effect, the nanogel is designed to function like pancreatic islet cells, which keep blood glucose at the right levels by secreting insulin and other hormones. These cells are destroyed in people with type 1 diabetes.
This is not the first time researchers have tried to design an “artificial pancreas” system that delivers insulin and other hormones automatically in response to glucose levels.
Some of the systems being developed use infusion pumps. For instance, earlier this year, researchers in Montreal reported some success with a dual-hormone artificial pancreas that is guided by an intelligent dosing algorithm.
Another approach uses hydrogels to measure and react to glucose levels, but Anderson and colleagues note these are slow to respond or lack mechanical strength, which allows the insulin to leak out when it shouldn’t.
With their nanogel, the MIT team thought they could design a robust, easier to use biocompatible system that could respond faster to changes in blood sugar.
Nanotechnology is a fairly new field that is growing rapidly as scientists learn how to manipulate matter at the atomic and molecular scale to create materials with remarkably varied and new properties.
The nanogel that the MIT team has developed is an “injectable and acid-degradable polymeric network” that looks and feels like toothpaste. It contains a mixture of oppositely charged nanoparticles that attract each other. This keeps the gel together and stops the nanoparticles drifting away once in the body.
To make the nanogel respond to increased acidity, Anderson and colleagues used dextran, a modified polysaccharide. Each nanoparticle in the gel holds spheres of dextran loaded with insulin and an enzyme that converts glucose into gluconic acid.
Glucose molecules can easily enter and diffuse through the gel. Thus when levels are high, lots of glucose passes through the gel and triggers release of the enzyme that converts it to gluconic acid. This increases acidity, which triggers the release of the insulin.
First the researchers tested the nanogel in test tubes using different levels of glucose and showed it could respond and release insulin.
When they tested it in live mice they found one injection of the nanogel kept blood glucose normal, for up to 10 days.
“A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days," they write. Because the nanogel is made mostly of polysaccharides, it is biocompatible and eventually degrades in the body. The team now wants to see if they can alter the gel so it responds more quickly to changes in glucose levels. Ideally they want it to react at the same speed as the islet cells in the pancreas: they release insulin very quickly once they sense high sugar levels. There is still some work to do before the gel is ready for human trials. For instance, the team wants to improve the gel’s ability to deliver, and to fine tune the dosage mechanism for human use. Funds from the Leona M. and Harry B. Helmsley Charitable Trust and the Tayebati Family Foundation helped finance the study. Written by Catharine Paddock PhD