Forget Needles. These Squid-Like Pills Will Spray Drugs Into the Gut Instead.

As a medical doctor, my mother isn’t afraid of needles. But when she recently began injecting insulin daily for her newly diagnosed diabetes, the shots became a frustrating nuisance.

A jab is a standard way to deliver insulin, antibodies, RNA vaccines, GLP-1 drugs such as Ozempic, and other large molecules. Compared to small chemicals—say, aspirin—these drugs often contain molecules that are easily destroyed if taken as pills, making injection the best option.

But no one likes needles. Discomfort aside, they can also cause infection, skin irritation, and other side effects. Scientists have long tried to avoid injections with other drug delivery options—most commonly, pills—if they can overcome the downsides.

This month, researchers from MIT and the pharmaceutical company Novo Nordisk took inspiration from squids to engineer ingestible capsules that burst inside the stomach and other parts of the digestive system.

The pills mimic a squid-like jet to “spray” their cargo into tissue. They make use of two spraying mechanisms. One works best in larger organs, such as the stomach and colon. Another delivers treatments in narrower organs, like the esophagus.

“These innovative devices deliver drugs directly” into the gut with minimal pain and no needles, the researchers wrote. When tested on dogs and pigs, the system delivered insulin, GLP-1-like hormones, and RNA-based molecules to target tissue in amounts similar to injections.

Delivery Headaches

Getting shots, whether for vaccines, antibodies, or cancer treatments, can be stressful. But there’s a reason these medicines require an injection rather than 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. Delivering them as a pill is extremely difficult.

Once swallowed, large molecules are often quickly destroyed by digestive enzymes or the liver, limiting their efficacy and increasing the likelihood of potential side effects. But of course, a pill is easier to take compared to getting a shot. So, despite the challenges, scientists have long sought to make pills that can replace injections for vaccines and other medicines.

Ink-Jet Squids

The new study looked to cuttlefish, squid, and octopi for inspiration.

These critters are versatile in their ability to adjust the pressure and direction of their ink jets. The team tapped into the same idea to distribute drugs in the gastrointestinal (GI) tract. By jetting medication directly into tissue, more can be absorbed before the body breaks it down.

“One aspect that I think is important here to appreciate is that the GI tract is composed” of many segments, and each has its own unique challenges, study author Giovanni Traverso told Nature. The stomach is like a balloon, for example, whereas the intestines are more sinewy. These differences require slightly different pressures for the therapy to work. In general, the pressure can’t be too high or it risks damaging the tissue. Pressure too low is also detrimental, in that it can’t deliver enough medication. The direction of the spray also matters.

“Part of the work we did was to define how much force needs to be applied so that the jet can go through the tissue,” said Traverso. They teased out how each part of the gastrointestinal tract absorbs drugs so they could dial in levels absorption without damage. Next, they engineered ingestible capsules that mimic the way squids and octopi project their ink.

The design has two jetting systems—one powered by coiled springs and the other compressed carbon dioxide—that are unleashed by humidity or acid and can target different tissues. The medication is encapsulated in normal-sized pills. One jet shoots the drugs into large organs, such as the stomach. The other jet targets smaller GI pathways, including the small intestines.

Prime Delivery

As proof of concept, the team used their system to deliver insulin in dogs and pigs suffering from diabetes-like conditions.

In one test, the system dramatically increased levels of the test medication—with effects similar to daily insulin injections. Other medications, such as GLP-1 drugs, RNA-type therapies, and antibodies—proteins that fight off infections and cancers—also accumulated at levels similar to injections. After releasing drugs, the biocompatible capsules passed through the digestive tract.

It’s still too early to know if the method would work in people. But the work suggests it just might be possible to one day swap out needles for pills.

“In contrast to a small needle, which needs to have intimate contact with the tissue, our experiments indicated that a jet may be able to deliver most of the dose from a distance or at a slight angle,” study author Graham Arrick said in a press release.

These pills could be used at home for people who need to take insulin or other injected drugs every day, making it easier to manage chronic diseases.

“This is an exciting approach which could be impactful for many biologics” that need to be injected, said Omid Veiseh at Rice University, who was not involved in the research, in the press release. It “is a significant leap forward in oral drug delivery.”

Image Credit: Meressa Chartrand on Unsplash