Gastrointestinal-resident, shape-changing microdevices extend drug release in vivo

Arijit Ghosh; Ling Li; Liyi Xu; Ranjeet P Dash; Neha Gupta; Jenny Lam; Qianru Jin; Venkata Akshintala; Gayatri Pahapale; Wangqu Liu; Anjishnu Sarkar; Rana Rais; David H Gracias; Florin M Selaru

doi:10.1126/sciadv.abb4133

Gastrointestinal-resident, shape-changing microdevices extend drug release in vivo

Sci Adv. 2020 Oct 28;6(44):eabb4133. doi: 10.1126/sciadv.abb4133. Print 2020 Oct.

Authors

Arijit Ghosh¹, Ling Li², Liyi Xu¹, Ranjeet P Dash^{3

4}, Neha Gupta¹, Jenny Lam^{3

4}, Qianru Jin¹, Venkata Akshintala², Gayatri Pahapale¹, Wangqu Liu¹, Anjishnu Sarkar¹, Rana Rais^{3

4}, David H Gracias^{5

6

7}, Florin M Selaru⁸

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
² Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
³ Johns Hopkins Drug Discovery, Baltimore, MD 21205, USA.
⁴ Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA.
⁵ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA. dgracias@jhu.edu fselaru1@jhmi.edu.
⁶ Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
⁷ Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.
⁸ Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. dgracias@jhu.edu fselaru1@jhmi.edu.

Abstract

Extended-release gastrointestinal (GI) luminal delivery substantially increases the ease of administration of drugs and consequently the adherence to therapeutic regimens. However, because of clearance by intrinsic GI motility, device gastroretention and extended drug release over a prolonged duration are very challenging. Here, we report that GI parasite-inspired active mechanochemical therapeutic grippers, or theragrippers, can reside within the GI tract of live animals for 24 hours by autonomously latching onto the mucosal tissue. We also observe a notable sixfold increase in the elimination half-life using theragripper-mediated delivery of a model analgesic ketorolac tromethamine. These results provide first-in-class evidence that shape-changing and self-latching microdevices enhance the efficacy of extended drug delivery.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Drug Delivery Systems*
Drug Liberation
Gastrointestinal Tract
Ketorolac Tromethamine*
Pharmaceutical Preparations

Substances

Pharmaceutical Preparations
Ketorolac Tromethamine

Grants and funding

R01 EB017742/EB/NIBIB NIH HHS/United States