Needles are one of the best ways to quickly deliver a drug, but for many, getting jabbed is an unpleasant experience. One in four adults has an intense fear of needles, which could deter people from vaccines or treatments. In some cases—like those with diabetes—skipping out on insulin shots could be life-threatening. While there are other routes of administration, such as through the mouth, drugs containing proteins or large molecules may not be absorbed as well orally. Or they wind up digested in the gastrointestinal tract. Scientists are eager to find less invasive alternatives to needles that still get drugs where they need to go.
Jean-Christophe Leroux, a professor in drug formulation and delivery at ETH Zurich in Switzerland, has one idea: transform an injectable into an oral drug absorbed through the buccal mucosa, the lining of the inner cheek. However, past research attempts at using cheek patches were foiled by the mouth’s wet surface, which weakened adhesion. For inspiration, Leroux and his colleagues turned to a master of underwater suction—the octopus.
In a new study published today in Science Translational Medicine, senior author Leroux and his team replicated the suckers found at the end of an octopus’s arms. Using 3D printing, they created a rubbery but strong suction patch that delivers drugs through the inner cheek. The majority of participants in a small human trial reported that the suction patch was a comfortable fit and they would prefer this method to needle injections.
“We have developed a very simple and easy to apply delivery system that could potentially replace injectables for several kinds of drugs,” Leroux says.
Octopuses use their grippy suckers to stay anchored in churning oceans or grab squirming prey. “The starting point was mimicking the good suction these creatures had to strongly stick to wet surfaces,” Leroux adds.
Their sucker-based model has a few advantages over swallowing a pill. Because the delivery system is placed in a cheek for absorption over time, the patch can be removed if needed. The domed cup also protects the drugs inside from dissolving in saliva.
A small trial in dogs showed drugs delivered by suction patch were effectively absorbed. The team applied patches, loaded with a diabetes tablet called desmopressin, to the mouths of three beagles. This peptide drug—a chain of amino acids—is poorly absorbed when taken orally. But after placing the suction patch, the researchers found higher concentrations of the drug in the dogs’ bodies. “We were really impressed by the level of absorption that we would get with such a simple system,” Leroux says.
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Still, when compared with drug concentrations in the dogs after injections, the patches weren’t quite as effective. One upside, however, was that the dogs appeared to be more comfortable with the patch, which remained on their cheeks for three hours without falling off or causing irritation.
The research makes a significant advance in using the inner cheek as an administration site for peptides, says David Brayden, a professor of advanced drug delivery in the University College Dublin in Ireland who was not affiliated with the study. Previous attempts to apply drugs via cheeks mostly used doses of small molecules that are easily absorbed, but not larger peptides. “No buccal formulation or device has ever been approved for peptide administration, despite a 20-year effort,” he says.
Humans seemed to tolerate the patches, too. Forty adult volunteers wore suction patches (loaded with water, not drugs) for 30 minutes. They added a strand of dental floss tied to the patch and people’s clothes to prevent accidental swallowing. During that half-hour, the volunteers walked, talked, and rinsed their mouths. Thirty-five of the 40 patches stayed on; the study authors say the fallen five were probably placed improperly.
An hour after applying the patch, 75 percent of people said they felt no discomfort. Examining the inner cheeks with an endoscopic camera, the researchers saw no scarring or changes to the mouths’ tissue. About 92 percent of people found the suction patch generally comfortable. And nearly 83 percent said if they had to take a drug daily, they’d prefer using the patch over a needle.
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“These are innovative studies that seek to identify new feasible methods and sites for [non-oral] drug delivery,” says Daniel Drucker, a professor of medicine at the University of Toronto in Canada who was not involved in the study. The canine trials showed the patch still has a pretty poor absorption of peptide drugs overall, he notes, but because people tolerated it so well, it could be an important foundation for future approaches to chronic disease therapies.
Larger safety trials—including wearing the device for longer than a half hour—will help refine how well people tolerate the patch. The researchers also need to show patients can wear it for simulated daily or weekly treatments. Once they have completed a larger safety trial, the next phase will be to test the effectiveness of the drug-loaded patch in people to assess how it compares with the absorption of pills and tablets.
This drug delivery system could be publicly available in a few years, if all goes well, Leroux says. Or sooner: “We could potentially be even faster because of the simplicity of the technology and because we can use drugs that are already approved.”
