Hyaluronic Acid-Conjugated Thermoresponsive Polymer-Based Bioformulation Enhanced Wound Healing and Gut Barrier Repair of a TNBS-Induced Colitis Injury Ex Vivo Model in a Dynamic Perfusion Device
(2024) In ACS Applied Materials and Interfaces 16(5). p.5382-5400- Abstract
Impairment of intestinal epithelium is a typical feature of inflammatory bowel disease (IBD) that causes leakage of bacteria and antigens from the intestinal lumen and thus results in persistent immune activation. Hence, healing and regeneration of the damaged gut mucosa is a promising therapeutic approach to achieve deep remission in IBD. Currently, available systemic therapies have moderate effects and are often associated with numerous side effects and malignancies. In this study, we aimed to develop a topical therapy by chemically conjugating a temperature-responsive polymer, i.e., poly(N-isopropylacrylamide), along with hyaluronic acid to obtain a sprayable therapeutic formulation that upon colon instillation adheres to the damaged... (More)
Impairment of intestinal epithelium is a typical feature of inflammatory bowel disease (IBD) that causes leakage of bacteria and antigens from the intestinal lumen and thus results in persistent immune activation. Hence, healing and regeneration of the damaged gut mucosa is a promising therapeutic approach to achieve deep remission in IBD. Currently, available systemic therapies have moderate effects and are often associated with numerous side effects and malignancies. In this study, we aimed to develop a topical therapy by chemically conjugating a temperature-responsive polymer, i.e., poly(N-isopropylacrylamide), along with hyaluronic acid to obtain a sprayable therapeutic formulation that upon colon instillation adheres to the damaged gut mucosa due to its temperature-induced phase transition and mucoadhesive properties. An ex vivo adhesion experiment demonstrates that this therapeutic formulation forms a thin physical coating on the mucosal lining at a physiological temperature within 5 min. Physicochemical characterization of (P(NIPAM-co-NTBAM)-HA) established this formulation to be biocompatible, hemo-compatible, and non-immunogenic. Prednisolone was encapsulated within the polymer formulation to achieve maximum therapeutic efficacy in the case of IBD-like conditions as assessed in a custom-fabricated perfusion-based ex vivo model system. Histological analysis suggests that the prednisolone-encapsulated polymer formulation nearly restored the mucosal architecture after 2,4,6-trinitrobenzenesulfonic acid-induced damage. Furthermore, a significant (p ≤ 0.001) increase in mRNA levels of Muc-2 and ZO-1 in treated groups further confirmed the mucosal epithelial barrier restoration.
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- author
- Mairal, Ayushi ; Mehrotra, Shreya ; Kumar, Anupam ; Maiwal, Rakhi ; Marsal, Jan LU and Kumar, Ashok
- organization
- publishing date
- 2024-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- ex vivo IBD model, hyaluronic acid, inflammatory bowel disease, mucosal healing, perfusion device, poly(N-isopropylacrylamide), TNBS, topical therapy
- in
- ACS Applied Materials and Interfaces
- volume
- 16
- issue
- 5
- pages
- 19 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:38266010
- scopus:85184665241
- ISSN
- 1944-8244
- DOI
- 10.1021/acsami.3c14113
- language
- English
- LU publication?
- yes
- id
- 77f4b461-fb4a-4b6e-91aa-a131b39f89d7
- date added to LUP
- 2024-03-01 15:02:06
- date last changed
- 2024-04-15 03:09:10
@article{77f4b461-fb4a-4b6e-91aa-a131b39f89d7,
abstract = {{<p>Impairment of intestinal epithelium is a typical feature of inflammatory bowel disease (IBD) that causes leakage of bacteria and antigens from the intestinal lumen and thus results in persistent immune activation. Hence, healing and regeneration of the damaged gut mucosa is a promising therapeutic approach to achieve deep remission in IBD. Currently, available systemic therapies have moderate effects and are often associated with numerous side effects and malignancies. In this study, we aimed to develop a topical therapy by chemically conjugating a temperature-responsive polymer, i.e., poly(N-isopropylacrylamide), along with hyaluronic acid to obtain a sprayable therapeutic formulation that upon colon instillation adheres to the damaged gut mucosa due to its temperature-induced phase transition and mucoadhesive properties. An ex vivo adhesion experiment demonstrates that this therapeutic formulation forms a thin physical coating on the mucosal lining at a physiological temperature within 5 min. Physicochemical characterization of (P(NIPAM-co-NTBAM)-HA) established this formulation to be biocompatible, hemo-compatible, and non-immunogenic. Prednisolone was encapsulated within the polymer formulation to achieve maximum therapeutic efficacy in the case of IBD-like conditions as assessed in a custom-fabricated perfusion-based ex vivo model system. Histological analysis suggests that the prednisolone-encapsulated polymer formulation nearly restored the mucosal architecture after 2,4,6-trinitrobenzenesulfonic acid-induced damage. Furthermore, a significant (p ≤ 0.001) increase in mRNA levels of Muc-2 and ZO-1 in treated groups further confirmed the mucosal epithelial barrier restoration.</p>}},
author = {{Mairal, Ayushi and Mehrotra, Shreya and Kumar, Anupam and Maiwal, Rakhi and Marsal, Jan and Kumar, Ashok}},
issn = {{1944-8244}},
keywords = {{ex vivo IBD model; hyaluronic acid; inflammatory bowel disease; mucosal healing; perfusion device; poly(N-isopropylacrylamide); TNBS; topical therapy}},
language = {{eng}},
number = {{5}},
pages = {{5382--5400}},
publisher = {{The American Chemical Society (ACS)}},
series = {{ACS Applied Materials and Interfaces}},
title = {{Hyaluronic Acid-Conjugated Thermoresponsive Polymer-Based Bioformulation Enhanced Wound Healing and Gut Barrier Repair of a TNBS-Induced Colitis Injury Ex Vivo Model in a Dynamic Perfusion Device}},
url = {{http://dx.doi.org/10.1021/acsami.3c14113}},
doi = {{10.1021/acsami.3c14113}},
volume = {{16}},
year = {{2024}},
}