Researchers have developed a special gel that could eventually enable insulin to be taken as a pill. In the long term, this might mean that millions of people with type 1 diabetes could swap daily insulin injections for a simple tablet. In rat experiments, the gel delivered up to 13 times more insulin across the intestinal wall than previous methods. The gel can also be used to administer other drugs.
One day, people with type 1 diabetes may no longer need to jab themselves in the stomach with an insulin pen – instead, they could take their medicine as a pill.
Insulin is a small protein, and stomach acid and digestive enzymes usually break down proteins long before they reach the intestine. And even if some survive the journey, it faces the next obstacle: the intestinal wall acts like a locked security gate that does not allow large molecules into the body.
Now, researchers have found a possible solution – a gel that can not only bring insulin safely through the stomach and into the bloodstream but may also be able to do this for many other advanced drugs that can currently only be administered by injection.
“Our experiments show that our solution not only assists insulin absorption from the intestine but also makes it more effective than other similar solutions,” explains a researcher behind the development, Hanne Mørck Nielsen, Professor at the Department of Pharmacy at the University of Copenhagen, Denmark.
The research has been published in Advanced Healthcare Materials.
Helper molecules that unlock the gut wall
When researchers try to make insulin in pill form, they use special excipients – permeation enhancers – that can briefly open the intestinal wall slightly so that large molecules can more easily pass through and enter the body.
Such excipients are becoming increasingly useful because many new drugs are made from peptides – small pieces of protein that the body otherwise has difficulty absorbing from the intestine.
Peptide drugs can do things that other drugs cannot, but if they are to be taken orally, they need to be protected.
“In addition, peptides are large molecules that need help to cross the intestinal wall. Researchers are therefore very closely examining permeation enhancers and how to use them optimally, but there is not yet any perfect solution,” says Hanne Mørck Nielsen.
The gel that carries insulin all the way through
The researchers mixed a harmless fat, C10, which temporarily makes the intestinal wall slightly more permeable, with a special thick gel. The gel binds to the insulin and protects it from stomach acid, and the fat helps it pass through the intestinal wall and into the bloodstream.
The aim was to create a product that could both protect insulin during transport through the digestive system and ensure that insulin is more effectively absorbed across the intestinal wall.
By freeze-drying insulin into the gel, the researchers hoped to preserve insulin’s structure and thus its biological activity.
The researchers tested their formulation in experiments with rats, which were given insulin orally in an ionogel, and found that, compared with various reference products, the newly developed product led to much greater absorption of insulin through the intestinal wall.
Thirteen-fold boost – and steady blood sugar for hours
In rats, up to 13 times more insulin reached the bloodstream than with the best earlier methods – and the animals experienced a steady and stable drop in blood sugar that lasted for five hours. This shows that the gel not only works but can also keep blood sugar down for many hours, just as proper insulin treatment should.
“This has implications for how much drug needs to be included in each dose. The more effective the absorption, the less drug is needed. This could also lower the risk of side-effects,” notes Hanne Mørck Nielsen.
Hanne Mørck Nielsen explains that the ionogel is probably so effective because it not only protects insulin but is also viscous and therefore remains in the intestine longer than, for example, a thin liquid.
C10 also promotes interaction between insulin and the intestinal wall, and overall, this gives insulin more time to penetrate the intestinal wall.
The researchers also tested the effect of C10 alone, but it did not improve insulin absorption through the intestinal wall.
“The combination of the physical state of the gel and C10 as a permeation enhancer in the formulation produces the good results,” explains Hanne Mørck Nielsen.
A gateway to many new pill-based treatments
Many strong excipients can damage the delicate tissue of the intestine, but that did not happen here. After five hours, the intestinal tissue looked normal, with no signs of damage.
“This is important, because this is often associated with such potent permeation enhancers. They are often incompatible with intestinal tissue and have a toxic effect, but we did not find that with our ionogel,” says Hanne Mørck Nielsen.
Hanne Mørck Nielsen explains that the researchers will further develop their gel so that it can be put into capsules that can be used to make not only oral versions of insulin but also oral versions of other peptide-based drugs.
In addition, the researchers will conduct new experiments to understand exactly how the ionogel works so well and whether it can be improved so that the body absorbs even more of the drug through the intestinal wall.
“If we can make it work for people, it could change the entire way insulin and similar drugs are administered. Not only would this be a relief for the people who need insulin, it could also save significant costs for healthcare systems and drug makers,” concludes Hanne Mørck Nielsen.
