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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Hookworm inspired, autonomous latching on the gastrointestinal mucosa extends the in vivo retention of a drug delivery device.

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.

Related collections

Most cited references 57

Record: found
Abstract: found
Article: not found

Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues.

Samuel Lai, Ying-Ying Wang, Justin Hanes (2009)

Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal (GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including conventional particle-based drug delivery systems, are efficiently trapped in human mucus layers by steric obstruction and/or adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on anatomical location, thereby strongly limiting the duration of sustained drug delivery locally. A number of debilitating diseases could be treated more effectively and with fewer side effects if drugs and genes could be more efficiently delivered to the underlying mucosal tissues in a controlled manner. This review first describes the tenacious mucus barrier properties that have precluded the efficient penetration of therapeutic particles. It then reviews the design and development of new mucus-penetrating particles that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained drug delivery for localized therapies in mucosal tissues.

0 comments Cited 367 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Emerging Frontiers in Drug Delivery.

Mark W Tibbitt, James Dahlman, Robert M Langer (2016)

Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.

0 comments Cited 230 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Self-Folding Thermo-Magnetically Responsive Soft Microgrippers

Joyce C Breger, ChangKyu Yoon, Rui Xiao … (2015)

Hydrogels such as poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) can be photopatterned to create a wide range of actuatable and self-folding microstructures. Mechanical motion is derived from the large and reversible swelling response of this cross-linked hydrogel in varying thermal or pH environments. This action is facilitated by their network structure and capacity for large strain. However, due to the low modulus of such hydrogels, they have limited gripping ability of relevance to surgical excision or robotic tasks such as pick-and-place. Using experiments and modeling, we design, fabricate, and characterize photopatterned, self-folding functional microgrippers that combine a swellable, photo-cross-linked pNIPAM-AAc soft-hydrogel with a nonswellable and stiff segmented polymer (polypropylene fumarate, PPF). We also show that we can embed iron oxide (Fe2O3) nanoparticles into the porous hydrogel layer, allowing the microgrippers to be responsive and remotely guided using magnetic fields. Using finite element models, we investigate the influence of the thickness and the modulus of both the hydrogel and stiff polymer layers on the self-folding characteristics of the microgrippers. Finally, we illustrate operation and functionality of these polymeric microgrippers for soft robotic and surgical applications.

0 comments Cited 188 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): SciAdv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date Collection: October 2020

Publication date (Electronic): 28 October 2020

Volume: 6

Issue: 44

Electronic Location Identifier: eabb4133

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 Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.

[6 ]Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.

Author notes

[*]

Present address: Charles River Laboratories, Ashland, OH 44805, USA.

[†]

Present address: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.

[‡ ]Corresponding author. Email: dgracias@ 123456jhu.edu (D.H.G.); fselaru1@ 123456jhmi.edu (F.M.S.)

Author information

Arijit Ghosh http://orcid.org/0000-0003-3449-2317

Ling Li http://orcid.org/0000-0003-4498-9466

Liyi Xu http://orcid.org/0000-0001-7946-4139

Neha Gupta http://orcid.org/0000-0002-7362-2383

Jenny Lam http://orcid.org/0000-0002-7915-3530

Qianru Jin http://orcid.org/0000-0003-3182-8188

Venkata Akshintala http://orcid.org/0000-0002-8909-1951

Gayatri Pahapale http://orcid.org/0000-0003-2434-0918

Wangqu Liu http://orcid.org/0000-0002-6526-5398

Anjishnu Sarkar http://orcid.org/0000-0001-9691-5851

Rana Rais http://orcid.org/0000-0003-4059-2453

David H. Gracias http://orcid.org/0000-0003-2735-4725

Florin M. Selaru http://orcid.org/0000-0001-7990-8238

Article

Publisher ID: abb4133

DOI: 10.1126/sciadv.abb4133

PMC ID: 7608789

PubMed ID: 33115736

SO-VID: 7ec9e446-bb9b-4cad-96de-a8174664079e

Copyright © 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).

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 22 February 2020

Date accepted : 11 September 2020

Funding

Funded by: doi http://dx.doi.org/10.13039/100000001, National Science Foundation;

Award ID: CMMI-1635443

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: R01EB017742

Custom metadata

Copyeditor Mjoy Azul

Data availability:

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

Read this article at

Abstract

Abstract

Related collections

Herbal Medicines Journal (Herb Med J)

Most cited references 57

Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues.

Emerging Frontiers in Drug Delivery.

Self-Folding Thermo-Magnetically Responsive Soft Microgrippers

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Cited by 34

Most referenced authors 532