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

doi:10.1016/j.ijpharm.2021.120717

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

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

102 Downloads (Pure)

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 language	English
Article number	120717
Number of pages	10
Journal	International Journal of Pharmaceutics
Volume	604
Early online date	18 May 2021
DOIs	https://doi.org/10.1016/j.ijpharm.2021.120717
Publication status	Published (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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ijpharm.2021.120717

1-s2.0-S0378517321005226-mainAuthor Accepted Manuscript, 5.11 MB

Cite this

Pabari, R. M., Tambuwala, M. M., Lajczak-McGinley, N., Aljabali, A., Kirby, B. P., Keely, S., & Ramtoola, Z. (2021). Novel polyurethane based particulate formulations of infliximab reduce inflammation in DSS induced murine model of colitis – A Preliminary study. International Journal of Pharmaceutics, 604, Article 120717. https://doi.org/10.1016/j.ijpharm.2021.120717

@article{b82277dc551c4f00a1ea2c953507e61b,

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

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.",

keywords = "Biomaterials, Colitis, Drug delivery, Infliximab, Particulate formulation",

author = "Pabari, {Ritesh M.} and Tambuwala, {Murtaza M.} and Natalia Lajczak-McGinley and Alaa Aljabali and Kirby, {Brian P} and Stephen Keely and Zebunissa Ramtoola",

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: {\textcopyright} 2021 Elsevier B.V.",

year = "2021",

month = jul,

day = "15",

doi = "10.1016/j.ijpharm.2021.120717",

language = "English",

volume = "604",

journal = "International Journal of Pharmaceutics",

issn = "0378-5173",

publisher = "Elsevier",

}

TY - JOUR

T1 - Novel polyurethane based particulate formulations of infliximab reduce inflammation in DSS induced murine model of colitis – A Preliminary study

AU - Pabari, Ritesh M.

AU - Tambuwala, Murtaza M.

AU - Lajczak-McGinley, Natalia

AU - Aljabali, Alaa

AU - Kirby, Brian P

AU - Keely, Stephen

AU - Ramtoola, Zebunissa

N1 - 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.

PY - 2021/7/15

Y1 - 2021/7/15

N2 - 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.

AB - 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.

KW - Biomaterials

KW - Colitis

KW - Drug delivery

KW - Infliximab

KW - Particulate formulation

UR - http://www.scopus.com/inward/record.url?scp=85110717831&partnerID=8YFLogxK

U2 - 10.1016/j.ijpharm.2021.120717

DO - 10.1016/j.ijpharm.2021.120717

M3 - Article

C2 - 34015378

SN - 0378-5173

VL - 604

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

M1 - 120717

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this