A Comparison of the Use of In-situ Gels and Oral Sulfasalazine in the Treatment of Colitis

This study aimed to compare the therapeutic efficacy of a sulfasalazine-loaded thermoresponsive in-situ gel with orally administered sulfasalazine in an acetic acid–induced rat colitis model, focusing on mucosal healing, inflammatory regulation, and apoptotic pathways. Colitis was induced in Wistar albino rats by intrarectal administration of 4% acetic acid. Animals were assigned to four groups: Control, Colitis, Colitis + Oral Sulfasalazine (100 mg/kg), and Colitis + In-Situ Gel. The in-situ gel was formulated with poloxamer 407, hyaluronic acid, and sulfasalazine. In vitro characterization included pH, gelation temperature, viscosity, rheology, and drug-release behavior. After 7 days of treatment, colon tissues were harvested for macroscopic, histopathological, and immunohistochemical analyses (Tumor necrosis factor alpha (TNF-α), Interleukin-1β (IL-1β), Caspase-3 (Cas-3)). Gene-expression profiles of Interleukin-6 (IL-6), Interleukin-10 (IL-10), Bcl-2 Associated X-protein (Bax), and B-Cell Leukemia/Lymphoma 2 (Bcl-2) were assessed via RT-qPCR. In vitro studies confirmed optimal gelation behavior and sustained drug release. Oral and gel treatments both reduced epithelial injury; however, the in-situ gel produced markedly superior mucosal preservation, reduced inflammatory infiltration, and lower TNF-α, IL-1β, and Cas-3 immunoreactivity. Gene-expression analysis showed significant reductions in Bax and IL-6, within the gel group. Sulfasalazine-loaded in-situ gel demonstrated superior anti-inflammatory, anti-apoptotic, and mucosal reparative effects compared with oral sulfasalazine. These findings support thermoresponsive in-situ gels as a promising localized therapeutic strategy for ulcerative colitis.