Editors' ChoiceBioengineering

Ingestible macromolecule injectors

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Science Translational Medicine  23 Oct 2019:
Vol. 11, Issue 515, eaaz3720
DOI: 10.1126/scitranslmed.aaz3720

Abstract

A next-generation ingestible device uses microneedles for macromolecule administration in the small intestine to avoid subcutaneous injections.

The oral administration of therapeutic macromolecules has been an extensive field of study for decades. Because macromolecules are not easily transported to the bloodstream through the gastrointestinal route, delivery via needles is typically required. In this regard, enhancing drug delivery to avoid subcutaneous injections could have a positive effect on millions of patients.

Building on previous work focused on intragastric macromolecule delivery, a new device developed by Abramson and colleagues inserts patches of 32 conical, drug-loaded microneedles 1 mm in height into the small intestinal mucosa. The pill-shaped capsule device can be swallowed, and after passing through the stomach, an osmotic-controlled spring propels a three-armed luminal unfolding microneedle injector (LUMI) that anchors the microneedles in the jejunum. LUMI slowly dissolves to deliver the drug load directly into the bloodstream while the capsule remnants are excreted. The authors tested microneedle penetration in vivo in swine, feeding pigs with multiple capsules, observing no animal discomfort, no residual devices, nor tissue perforation. Similar results were observed in human small intestine ex vivo experiments using samples from patients of different ages. As a proof-of-concept for macromolecule administration, the authors treated swine with human insulin that diabetic patients self-inject daily, tracking blood plasma of hormone and glucose over several hours. Overall, LUMI achieved an excellent pharmacokinetic profile, with a faster systemic uptake and better bioavailability than subcutaneous dosing of human insulin.

Although further tests, such as use of animal models of disease, are needed prior to evaluating LUMI’s potential use in humans, this innovative device enabling tight regulation of drug release could improve patient treatment. As the authors claim, controlled oral delivery of macromolecules—like vaccines, antibodies, enzymes, hormones, and RNA, among others—could represent a new era for personalized medicine.

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