Intracolonic Treatment with a Rifamycin SV In Situ Gelling Formulation Ameliorates Macroscopic and Histological Damage in an Acute Rat Model of Oxazolone-Induced Colitis: A Proof-of-Concept Study.

Background/

Objectives

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colonic mucosa, resulting from a complex interplay between epithelial barrier dysfunction, dysregulated immune responses, and alterations in the gut microbiota. Despite advances in therapeutic strategies, current treatments for UC remain suboptimal. Many conventional and biologic therapies are associated with systemic side effects due to non-specific distribution, which can limit their long-term use. Novel acting therapies are needed for ulcerative colitis. This study evaluated the efficacy of intracolonic Rifamycin SV in situ gelling formulation (CB-01-35) in a rat model of oxazolone-induced colitis.

Methods

Acute colitis was induced in female Wistar rats using oxazolone. Animals were treated for three days with CB-01-35 (80 mg/kg, intracolonic), Vehicle, Asacol, or dexamethasone. Clinical parameters, colon weight, macroscopic damage score (MDS), mucosal damage area, and histological score were assessed.

Results

CB-01-35 significantly reduced MDS compared with Vehicle (p < 0.05) and showed a trend toward reduced mucosal damage area (p = 0.06). Histological analysis confirmed significant improvement, with reduced leukocyte infiltration and epithelial damage. No significant effects were observed on body weight or colon weight. Comparator treatments showed limited or inconsistent efficacy.

Conclusions

CB-01-35 demonstrated therapeutic activity in this preclinical model, supporting further investigation as a locally acting treatment for colitis. These findings represent an initial proof-of-concept and warrant confirmation in larger and mechanistic studies.