Novel polyurethane based particulate formulations of infliximab reduce inflammation in DSS induced murine model of colitis – A Preliminary study

Ritesh M. Pabari, Murtaza M. Tambuwala, Natalia Lajczak-McGinley, Alaa Aljabali, Brian P Kirby, Stephen Keely, Zebunissa Ramtoola

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5 Citations (Scopus)
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Abstract

Our recent study showed that novel infliximab (INF) loaded polyesterurethane (INF-PU) and INF-PU-PEG particulate formulations reduced inflammation in an in-vitro epithelial inflammation model. In this study we investigated therapeutic potential of novel INF-PU and INF-PU-PEG particulate formulations to reduce inflammation in a dextran sodium sulfate (DSS) induced murine model of colitis. Severity of colitis was assessed by measurement of disease activity index (DAI) score, inflammatory markers (neutrophil infiltration, TNFα) and histological score. Treatment groups orally administered with INF-PU and INF-PU-PEG particulate formulations showed improvement in the clinical signs of colitis, similar to that observed with intraperitoneally administered INF, in both, moderate and severe DSS induced colitis model. This was related to a significant reduction in inflammatory cytokines, resulting in a significant reduction in histological score (ANOVA; p < 0.05), indicative of mucosal healing, a key goal of IBD therapy. This could be attributed to its targeted delivery to the inflamed colon and higher permeation of these particulate formulations across the inflamed colonic mucosa, as observed by the confocal images, resulting in local inhibition of TNFα at its site of production. These promising preliminary results warrant further investigation of orally administered INF and its novel particulate formulations in a wider preclinical study.

Original languageEnglish
Article number120717
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume604
Early online date18 May 2021
DOIs
Publication statusPublished (in print/issue) - 15 Jul 2021

Bibliographical note

Funding Information:
The authors gratefully acknowledge research funding from the Irish Research Council (IRC) awarded to Ritesh M. Pabari (GOIPD/2014/403). Authors would like to thank Gemma Mernihan and Brenton Cavanagh for help with confocal microscopy.

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • Biomaterials
  • Colitis
  • Drug delivery
  • Infliximab
  • Particulate formulation

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