Dynamic omnidirectional adhesive microneedle system for oral macromolecular drug delivery

Oral drug administration remains the preferred route for patients and health care providers. Delivery of macromolecules through this route remains challenging because of limitations imposed by the transport across the gastrointestinal epithelium and the dynamic and degradative environment. Here, we present the development of a delivery system that combines physical (microneedle) and nonphysical (enhancer) modes of drug delivery enhancement for a macromolecule in a large animal model. Inspired by the thorny-headed intestinal worm, we report a dynamic omnidirectional mucoadhesive microneedle system capable of prolonged gastric mucosa fixation. Moreover, we incorporate sodium N-[8-(2-hydroxybenzoyl) amino] caprylate along with semaglutide and demonstrate enhanced absorption in swine resistant to physical displacement in the gastric cavity. Meanwhile, we developed a targeted capsule system capable of deploying intact microneedle-containing systems. These systems stand to enable the delivery of a range of drugs through the generation and maintenance of a privileged region in the gastrointestinal tract.

Automated summary

Oral drug administration remains the preferred route for patients and health care providers, but delivering macromolecules through this route is challenging. In this study, a delivery system combining physical and nonphysical drug delivery enhancement modes was developed and tested in a large animal model. Inspired by a thorny-headed intestinal worm, a dynamic omnidirectional mucoadhesive microneedle system was created, which showed prolonged fixation on the gastric mucosa. The incorporation of sodium N-[8-(2-hydroxybenzoyl)amino] caprylate along with semaglutide demonstrated enhanced absorption in swine, and a targeted capsule system was developed to deploy intact microneedle-containing systems, enabling drug delivery in a privileged region of the gastrointestinal tract.