As a doctor, my mother is not afraid of needles. But when she recently started injecting insulin daily for her newly diagnosed diabetes, the injections became a frustrating burden.
A shot is a standard way to administer insulin, antibodies, RNA vaccines, GLP-1 drugs such as Ozempic and other large molecules. Compared to small chemicals, for example aspirin, these drugs often contain molecules that are easily destroyed when taken in pill form, making injection the best option.
But no one likes needles. Aside from the discomfort, they can also cause infections, skin irritation and other side effects. Scientists have long tried to avoid injections with other forms of drug delivery (usually pills) if they can overcome the disadvantages.
This month, researchers from MIT and the pharmaceutical company Novo Nordisk took inspiration from squids to develop ingestible capsules that burst in the stomach and other parts of the digestive system.
The pills mimic a squid-like beam to ‘spray’ their payload into the tissue. They use two spray mechanisms. It works best in larger organs, such as the stomach and large intestine. Another delivers treatments in narrower organs, such as the esophagus.
“These innovative devices deliver medications directly” into the intestines, with minimal pain and without needles, the researchers wrote. In tests on dogs and pigs, the system delivered insulin, GLP-1-like hormones and RNA-based molecules to target tissue in amounts comparable to injections.
Headache upon delivery
Getting shots, whether for vaccines, antibodies or cancer treatments, can be stressful. But there’s a reason these drugs require an injection instead of a pill: they’re usually made of larger biological molecules. These include antibodies or RNA-based vaccines that rely on proteins and other complex molecules. It is extremely difficult to deliver them as a pill.
Once ingested, large molecules are often quickly destroyed by digestive enzymes or the liver, limiting their effectiveness and increasing the likelihood of possible side effects. But of course a pill is easier to take than an injection. So despite the challenges, scientists have long been trying to create pills that could replace injections for vaccines and other medicines.
Inkjet squids
The new research looked to cuttlefish, cuttlefish and octopuses for inspiration.
These critters are versatile in their ability to adjust the pressure and direction of their ink jets. The team used the same idea to distribute drugs in the gastrointestinal tract. By injecting drugs directly into the tissue, more can be absorbed before the body breaks it down.
“One aspect that I think is important to appreciate is that the gastrointestinal tract is made up of many segments, and each has its own unique challenges,” study author Giovanni Traverso said. Nature. For example, the stomach resembles a balloon, while the intestines are more sinewy. These differences require slightly different pressures for the therapy to work. In general, the pressure should not be too high, otherwise there is a risk of damaging the tissue. Too low pressure is also harmful, because not enough medication can be administered. The direction of the spray is also important.
“Part of the work we did was determining how much force needs to be applied for the beam to pass through the tissue,” Traverso said. They teased out how each part of the gastrointestinal tract absorbs drugs so they could dial in absorption levels without causing damage. They then developed ingestible capsules that mimic the way squids and octopuses project their ink.
The design has two jet systems – one powered by coil springs and the other by compressed carbon dioxide – that are released by moisture or acid and can target different tissues. The drug is encapsulated in normal-sized pills. One jet plane shoots the drugs into large organs, such as the stomach. The other plane targets smaller gastrointestinal routes, including the small intestine.
First delivery
As a proof of concept, the team used their system to deliver insulin to dogs and pigs suffering from diabetes-like conditions.
In one test, the system dramatically increased concentrations of the test medication, with effects comparable to those of daily insulin injections. Other drugs, such as GLP-1 drugs, RNA-like therapies and antibodies (proteins that fight infections and cancer) also piled up in amounts comparable to injections. After drug release, the biocompatible capsules passed through the digestive tract.
It is still too early to know whether the method would work in humans. But the work suggests it might one day be possible to swap needles for pills.
“Unlike a small needle, which must have intimate contact with tissue, our experiments indicated that a jet can deliver most of the dose from a distance or at a small angle,” study author Graham Arrick said in a study. press release.
These pills can be used at home for people who need to take insulin or other injected medications every day, making it easier to deal with chronic diseases.
“This is an exciting approach that could have an impact on many biologics” that need to be injected, Omid Veiseh of Rice University, who was not involved in the study, said in the press release. It “is a significant leap forward in oral drug delivery.”
Image credits: Meressa Chartrand on Unsplash