Researchers have developed a suction cup that allows medications to be absorbed through the mucosal lining of the cheeks.
This new approach could spare millions of patients the pain and fear associated with injections.
Many of today’s medications belong to groups of relatively large molecules such as peptides. They are used to treat a wide range of diseases, including diabetes, obesity, and prostate cancer.
Unfortunately, taking these medications in tablet form is out of the question in most cases because they would break down in the digestive tract or remain too large to reach the bloodstream. Consequently, the patient’s only option is to receive their medication via injection.
“It’s an entirely new method of delivering medications that could spare millions of people the fear and pain associated with injections,” says Nevena Paunović, who works at the Chair of Drug Formulation and Delivery at ETH Zurich.
The mucosal lining of the cheek isn’t particularly suitable for delivering medication to the bloodstream. Its dense tissue has so far presented a major obstacle, especially for large molecules like peptides. But the researchers are now about to change this with the suction cup.
Patients press the suction cup—which measures around 10 millimeters in diameter and six millimeters in height (about .39 inches and .23 inches)—onto the lining of their cheek with two fingers. This produces a vacuum that stretches the lining, making it more permeable to the drug contained within the cup’s dome-shaped hollow. But that alone isn’t enough for the drug to reach the blood vessels.
The researchers supplemented the drug with an endogenous agent that turns the cell membranes into fluid, allowing the drug to penetrate to the deeper layers of tissue. Patients are advised to keep the suction cup on the inside of their cheek for a few minutes. That’s enough time for the drug to dissolve in saliva and enter their bloodstream directly via the now permeable mucosal lining.
Compared to the few oral formulations of peptides on the market, the suction cup supports the delivery of a wide range of medications without the need for any major technological adjustments.
The original idea for the suction cup came from Zhi Luo, a former postdoc working with Jean-Christophe Leroux, professor and lead of the Chair of Drug Formulation & Delivery.
At dinner with friends, he suddenly noticed 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 drugs in place on slippery surfaces. But before the team could turn the idea into a working prototype, they had a few problems to solve. The biggest challenge was to identify the right shape of the suction cup.
“We had to find out what geometry and how much of a vacuum were required to hold the suction cup in place on the mucosal lining of the cheek and to stretch it sufficiently without causing any damage,” says David Klein Cerrejon of the Chair of Drug Formulation & Delivery.
In addition to producing several prototypes, which the researchers designed and 3D printed themselves, this called for numerous tests using the mucosal lining of a pig’s cheek. To find the right penetration-promoting agent, the researchers tested a broad range of substances of varying concentrations and under a microscope evaluated how the different mixtures penetrated the tissue.
“Since the suction cup is a completely new delivery system, we had to experiment extensively before finding the right substance. It turned out that natural, endogenous substances are extremely well suited for this task,” Klein Cerrejon says.
The researchers then moved on to testing their suction cup and the penetration-promoting agent in authorized trials on dogs, because dogs and humans have very similar mucosal lining in their cheeks. No dogs were harmed by the testing. The researchers were pleased with the results.
“We could see from the blood samples that the suction cup efficiently delivered medications to the dogs’ bloodstreams,” Klein Cerrejon says.
So far, the team has also tested the empty suction cup on 40 people. Not only did the suction cup remain attached for 30 minutes but also received positive feedback from the people testing it. Most of the volunteers said that they would by far prefer the new delivery system over an injection.
The researchers will have to carry out further tests with this new delivery system in preparation for conducting a clinical trial on healthy volunteers. There are also several regulatory hurdles to clear before the suction cup hits the market. For this, the researchers need strong partners and sufficient funding.
The study is published in Science Translational Medicine.
Source: Christoph Elhardt for ETH Zurich
