Researchers created a self-applying suction patch to improve drug absorption in part by drawing inspiration from the distinctive structural characteristics of octopus suckers. The noninvasive platform technology uses chemical permeation enhancers and mechanical stretching of the buccal mucosa (the inside of the mouth) to help macromolecular drugs get into the body more quickly.
The research article, “Boosting systemic absorption of peptides with a bioinspired buccal-stretching patch,” was published in Science Translational Medicine.
The bitter pill
Not all medications, especially those with complex molecular structures like biologics or large proteins, can simply be swallowed whole. Many biologics, which can be extremely large on the molecular scale, are administered via injection. Companies like Rani Therapeutics are exploring ways to increase drug absorption using more invasive physical methods like microneedle injection in the gastrointestinal (GI) tract. Although other systemic strategies, such as pulmonary inhalation and nasal administration, have been investigated, it has long been a research interest in the pharmaceutical sciences to find new formulation strategies to overcome obstacles in the delivery of biologics.
Despite decades of research into effective permeation-enhancing technologies, the FDA has only approved two oral peptide formulations in the past three years (semaglutide and octreotide). The absolute oral bioavailability of these peptides is often less than one percent, and variability stays high, even when large amounts of permeation enhancers are given and the formulation is taken under strict intake conditions.
Peptide systemic delivery via transdermal systems, like iontophoretic devices and microneedles, has the potential to be highly efficient. However, the complexity of the manufacturing or application processes hinders them.
Compared to other delivery sites, the buccal region has several advantages, including easy accessibility, tolerance of mechanical disruption, and avoidance of the hepatic first-pass effect. In addition, the mild pH and lower proteolytic activity make the oral cavity much less hostile to peptides than the stomach and the small intestine. However, the human buccal epithelium is composed of about 50 layers of cells with a thickness of 0.05 centimeters, and the permeation of macromolecules across the buccal mucosa has met with only limited success, even in the presence of permeation enhancers.
Get a grip
To speed up the process of macromolecular drugs entering the body, Zhi Luo, David Klein Cerrejon, and others created a brand-new noninvasive platform technology that combines chemical permeation enhancers with mechanical stretching of the buccal mucosa. Their idea was that a mechanical disturbance could temporarily change how the cells in the mucosa are organized. This would make the gaps between the cells bigger, letting more drugs pass through.
They were inspired by the way octopuses’ sucker patches are designed so that they could effectively stick to and stretch the mucosal tissue simultaneously. When an octopus sucker touches something, its flexible outer ring molds to the object, sealing it off from water. The sucker’s muscles then tighten, creating suction.
To make something similar, the researchers created a suction cup orifice design (SCOD). This design works by placing the SCOD, compressing it, deforming the mucosa, letting drugs enter and pass through it, and then removing the SCOD. Based on this design, they 3D-printed suction patches that were 1.1 cm in diameter and 0.6 cm high to make them less painful and easier for patients to use. These patches could hold more than 50 mg of a drug.
Desmopressin is a peptide drug not well absorbed by the body when taken by mouth. This suction patch made the drug up to two orders of magnitude more bioavailable in dogs than the commercial tablet form. It was also possible to get systemic exposure similar to the approved oral semaglutide tablet without making any other changes. Lastly, a first-in-human study with 40 healthy people confirmed that the dosage form was acceptable. This supports the clinical transferability of this simple but effective platform technology.
The bioinspired SCOD technology presented here is noninvasive, easy to use, and readily self-applicable by patients. Because it is simple and can be put together in different ways, this technology could be used to deliver a wide range of chemicals that are quickly broken down or not absorbed well by the body. Ensuring long-term safety and patient acceptance are the most important things for successfully translating the formulation.