Intestinal organoids containing poly(lactic-co-glycolic acid) nanoparticles for the treatment of inflammatory bowel diseases

Zahra Davoudi, Nathan Peroutka-Bigus, Bryan Bellaire, Michael Wannemuehler, Terrence A. Barrett, Balaji Narasimhan, Qun Wang

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Inflammatory bowel disease (IBD) causes inflammation to the gastrointestinal tract. Local administration of anti-inflammatory drugs such as 5-aminosalicylic acid (5-ASA) can alleviate the symptoms of IBD. The application of nanoparticles for IBD treatment in direct rectal administration showed high drug availability and treatment efficacy. However, relying on size-dependent adsorption of smaller particles is not sufficient for making the formulation capable of targeting. Intestinal organoids can improve the functionality of the nanoparticles due to their ability to adsorb small nanoparticle inside the lumen and attach to the damaged area. In this study, intestinal organoids were used as carriers of 5-ASA-loaded poly(lactic-co-glycolic acid) nanoparticles. The nanoparticle sizes, confirmed by scanning electron microscopy, were 200–300 nm and the zeta potential were negative. The nanoparticles did not have any noticeable pernicious effect on organoid growth and viability. After mixing the nanoparticles with Matrigel and organoids, Rhodamine B loaded inside the nanoparticles was highly detected inside the organoid's lumen after 3 days by confocal fluorescent microscopy and no longer detected in the lumen after day 4. It may be attributed to the ability of the lumen to digest particles. Thus, the organoid Trojan horse system is a possible approach for delivering drugs to inflamed areas.

Original languageEnglish
Pages (from-to)876-886
Number of pages11
JournalJournal of Biomedical Materials Research - Part A
Volume106
Issue number4
DOIs
StatePublished - Apr 2018

Bibliographical note

Funding Information:
Additional Supporting Information may be found in the online version of this article. Correspondence to: Q. Wang; e-mail: qunwang@iastate.edu Contract grant sponsor: Crohn’s & Colitis Foundation of America (CCFA) Career Award; contract grant number: 348137 Contract grant sponsor: PhRMA Foundation; contract grant numbers: RSGTMT17, Research Starter Award No. RSGTMT17 Contract grant sponsor: McGee-Wagner Interdisciplinary Research Foundation Contract grant sponsor: National Institutes of Health; contract grant number: R01DK095662 Contract grant sponsor: Veterans Affairs Merit Award; contract grant number: I01CX001353

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

Keywords

  • PLGA
  • inflammatory bowel disease
  • intestinal stem cells
  • nanoparticles
  • organoids

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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