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
posted on 2024-01-24, 18:36authored byAyushi Mairal, Shreya Mehrotra, Anupam Kumar, Rakhi Maiwal, Jan Marsal, Ashok Kumar
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.