The octopus was the inspiration: Researchers have developed a system through which medications that previously had to be injected can be administered via the oral mucosa. A small suction cup gently stretches the tissue and, in combination with a natural loosening substance, makes it permeable to difficult-to-move active ingredients. The concept is easy to use, well tolerated and effective, as shown by previous tests on animals and humans. In collaboration with industry partners, the team now wants to bring the practical medication suction cups onto the market as quickly as possible.
Tablets can simply be washed down with a little water and the active ingredients are then absorbed through the digestive system. Unfortunately, this convenient dosage form does not work with many modern active ingredients: more and more drugs are being developed that consist of relatively large molecules such as peptides that do not pass into the blood or are broken down in the digestive tract. Therefore they have to be administered via the unpleasant and complicated form of injection. Plaster systems with tiny needles for administration or special nasal sprays have already been developed. However, the effectiveness, tolerability and practicality of these concepts have so far left much to be desired. The concept developed by a team from the Swiss Federal Institute of Technology in Zurich (ETH) can now apparently score points in these aspects.
As first author Zhi Luo reports, the development of the suction cup concept began with a dinner in which half a peppercorn stuck to the mucous membrane in his oral cavity. This gave him the idea that it might be possible to attach an object to the inside of the cheeks, which could then transfer active ingredients through the mucous membrane into the circulatory system. He and his colleagues ultimately looked to the octopus for inspiration. The suction cups of these marine animals can attach themselves very effectively to slippery and flexible surfaces. In addition, this creates a negative pressure, which can lead to increased permeability of the tissue sucked in. But from the idea to the first prototype, there were still a few problems that had to be solved.
Sucked in and gently softened
The biggest challenge was finding the right shape for the suction cup: “We had to determine what geometry and how much negative pressure is necessary so that the suction cup sticks to the cheek mucosa and stretches it enough without damaging it,” says Co-author David Klein Cerrejon. The researchers created various versions using 3D printing from elastomer materials and tested them on the cheek mucous membranes of pigs. Ultimately, a suction cup about one centimeter wide and six millimeters high made of the soft material, which has no health problems, turned out to be optimal. A patient can easily press it against the cheek mucosa with two fingers. The resulting negative pressure causes the mucous membrane to stretch and become more permeable to an active ingredient that is located in the dome-shaped cavity of the suction cup.
But as it turns out, this is not quite enough to effectively transfer substances into the blood vessels. But as experiments have shown, this can be improved quite easily by adding a substance that loosens the cell membranes. “It turned out that natural and endogenous substances are ideal for this task,” says Klein Cerrejon. Specifically, it was shown that the substance sodium taurocholate can gently help the active ingredient penetrate from the dome of the suction cup into the deeper tissue layers of the stretched mucous membrane. The scientists emphasize that the system can be used to administer many different drugs.
On the way to market readiness
The team has already tested the extent to which the concept delivers what it promises on dogs whose cheek mucosa is similar to that of humans. This demonstrated problem-free tolerability and effective transfer of the test substance used within just a few minutes. “We saw from blood samples that the suction cup effectively transports the drug into the dogs’ bloodstream,” says Klein Cerrejon. The researchers have already tested the suction cup on 40 volunteers without filling. As it turned out, they were able to attach the suction cup without any problems and it remained firmly attached to the inside of the cheeks until they removed it again after 30 minutes. Most test subjects stated that they would much prefer the new form of administration to an injection, the developers report.
After further clinical tests, they now want to bring the concept to market maturity as quickly as possible. Pharmacist Nevena Paunović from ETH is in charge of this: “We already have a prototype and a technology that is already patented. The next step is to produce the suction cup so that it meets current pharmaceutical regulations.” Finally, she once again emphasizes the potential: “It is a completely new method of administering drugs that could save millions of people the painful or unpleasant experience of an injection,” says Paunović.
Source: Swiss Federal Institute of Technology Zurich, specialist article: Science Translational Medicine, doi: 10.1126/scitranslmed.abq1887