Patches inspired by octopus tentacles to deliver drugs from the inside of the cheek

2023-09-28 12:26:52

Many of today’s medications belong to relatively large groups of molecules, such as peptides. They are used to treat a wide range of diseases, such as diabetes, obesity and prostate cancer. In most cases it is not possible to take these medications in tablet form because they break down in the digestive tract or are too large to reach the bloodstream. Consequently, the only option for the patient is to receive the medication through an injection.

Now, a group of researchers from the ETH Zurichin Switzerland, has developed adhesive patches inspired by octopus suction cups that allow difficult-to-absorb drugs to be administered by pressing them on the inside of the cheeks.

With these patches it is possible to deliver medications composed of large molecules, such as peptides, into the bloodstream through the mucosa of the cheeks. The group is led by David Klein Cerrejón y Nevena Paunovićwho work in the Chair of Drug Formulation and Administration of the Swiss institution, directed by Jean-​Christophe Leroux.

With these patches it is possible to deliver medications composed of large molecules, such as peptides, into the bloodstream through the mucosa of the cheeks.

“It is a completely new method of administering medicines that could save millions of people from the fear and pain associated with injections,” says Paunović. The team plans to commercialize this system through the company Transire Bio.

The method of use consists of press the rubber suction cup with two fingers, which measures about ten millimeters in diameter and six millimeters in height, on the mucosa of the inside of the cheek. This produces a vacuum that stretches the liner, making it more permeable to the drug contained in the dome-shaped recess of the suction cup. But this is not enough for the drug to reach the blood vessels.

For this reason, the researchers have complemented the drug with an endogenous agent that fluidizes cell membranes, allowing the drug penetrates the deepest layers of tissue. Patients are advised to keep the suction cup on the inside of the cheek for a few minutes. That time is enough for the drug to dissolve in saliva and penetrate directly into the bloodstream through the now permeable mucosa.

Compared to the few oral formulations of peptides on the market, the suction cup developed by the ETH researchers allows the administration of a wide range of medications without the need for major technological adjustments.

The team of researchers has been inspired by the suction cups on octopus tentacles to design the patches. / Luo Z et al /EFE

Design challenges

The original idea for the suction cup came from Zhi Luo, former postdoc of Professor Leroux at ETH and now a professor working in China. During a dinner with friends, he suddenly realized that he had half a peppercorn stuck to the inside of his oral cavity. Although uncomfortable, this experience gave him the idea of ​​how to keep medications in place on slippery surfaces. But before the team could turn the idea into a working prototype, they had to solve some problems.

We had to figure out what geometry and how much vacuum were needed to keep the suction cup in place on the cheek mucosa and stretch it enough without causing damage.

David Klein Cerrejón (ETH Zurich)

The biggest challenge was designing the suction cup. “We had to figure out what geometry and how much vacuum were needed to keep the suction cup in place on the cheek mucosa and stretch it enough without causing damage,” explains Klein Cerrejón.

In addition to manufacturing several prototypes, which the researchers themselves designed and 3D printed, it was necessary to carry out numerous tests with the mucosa of a pig’s cheek.

Tests on dogs and humans

The researchers then tested the patch and the stimulating agent of penetration in authorized tests with dogs, since the cheek mucosa of dogs and humans is very similar. No animals were injured. “In the blood samples we were able to verify that the patch effectively transported the medications to the dogs’ bloodstream,” says Klein Cerrejón.

So far, the team has also tested the cupping on 40 people. The patch remained attached for 30 minutes, and most volunteers who tested it said they would much prefer the new delivery system to an injection.

“We have a prototype and we have already patented the technology. Our next step is to manufacture the suction cup so that it meets the pharmaceutical regulations current”, explains Paunović, who received her doctorate from Leroux and is a pharmacist by training.

We have a prototype and we have already patented the technology. Our next step is to manufacture the suction cup in a way that complies with current pharmaceutical regulations.

Nevena Paunović (ETH Zurich)

Researchers will need to do more testing with this new delivery system to prepare for a clinical trial in healthy volunteers.

Several regulatory hurdles will also need to be overcome before the patch goes on the market. The peptide business represents billions for the pharmaceutical industry and several companies have already expressed interest, according to the authors.

Reference:

Luo Z, Klein Cerrejon D, Römer S, Zoratto N, Leroux JC: “Boosting systemic absorption of peptides with a bioinspired buccal-​stretching device” Science Translational Medicine (2023)

Rights: Creative Commons.