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Science. 2019 Feb 8;363(6427):611-615. doi: 10.1126/science.aau2277.

An ingestible self-orienting system for oral delivery of macromolecules.

Author information

1
Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Global Research Technologies, Global Drug Discovery, and Device R&D, Novo Nordisk A/S, Copenhagen, Denmark.
4
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5
Department of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden.
6
Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. rlanger@mit.edu ctraverso@bwh.harvard.edu.
7
Media Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
8
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
9
Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise's ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator's safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.

Comment in

PMID:
30733413
PMCID:
PMC6430586
[Available on 2020-02-08]
DOI:
10.1126/science.aau2277

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