A self-unfolding proximity enabling device for oral delivery of macromolecules

• Published in: Journal of controlled release Vol. 361; pp. 40 - 52
• Main Authors: Ghavami, Mahdi, Pedersen, Jesper, Kjeldsen, Rolf Bech, Alstrup, Aage Kristian Olsen, Zhang, Zhongyang, Koulianou, Vasiliki, Palmfeldt, Johan, Vorup-Jensen, Thomas, Thamdrup, Lasse Højlund Eklund, Boisen, Anja
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2023
• Subjects: Drug delivery device; Elastomer; Ingestible device; Oral delivery of macromolecule; Oral insulin; Polydimethylsiloxane (PDMS); Oral insulin; Ingestible device; Oral delivery of macromolecule; Drug delivery device; Elastomer; Polydimethylsiloxane (PDMS)
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2023.07.041

Oral delivery of macromolecules remains highly challenging due to their rapid degradation in the gastrointestinal tract and poor absorption across the tight junctions of the epithelium. In the last decade, researchers have investigated several medical devices to overcome these challenges using various approaches, some of which involve piercing through the intestine using micro and macro needles. We have developed a new generation of medical devices called self-unfolding proximity enabling devices, which makes it possible to orally deliver macromolecules without perforating the intestine. These devices protect macromolecules from the harsh conditions in the stomach and release their active pharmaceutical ingredients in the vicinity of the intestinal epithelium. One device version is a self-unfolding foil that we have used to deliver insulin and nisin to rats and pigs respectively. In our study, this device has shown a great potential for delivering peptides, with a significant increase in the absorption of solid dosage of insulin by ∼12 times and nisin by ∼4 times in rats and pigs, respectively. With the ability to load solid dosage forms, our devices can facilitate enhanced absorption of minimally invasive oral macromolecule formulations. [Display omitted] •Advancing oral delivery: optimizing self-unfolding foil (SUF) as an effective oral delivery device for macromolecules•Enhanced visualization: incorporating contrast materials for in vivo tracking of SUFs•Boosting insulin bioavailability in rats: achieving 12-fold increase using SUFs•Scaling up success: optimizing SUFs for efficient oral delivery device in large animals•Maximizing nisin bioavailability: a 4-fold increase was achieved by oral administration of SUFs in pigs