Application of thermo-responsive polymers as an enema formulation for the treatment of ulcerative colitis.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain and diarrhea. Although 5-aminosalicylic acid (5-ASA) enemas are widely used, conventional formulations can result in rectal leakage and poor retention, substantially impairing the therapeutic efficacy and quality of life (QOL) of patients. To address these limitations, in this study, we developed a thermoresponsive and mucoadhesive dual-functionality enema system by combining poloxamer with carbopol (CP). This study optimized a thermoresponsive and mucoadhesive rectal gel formulation for 5-ASA and evaluated its physicochemical properties and therapeutic efficacy in experimental ulcerative colitis. The formulation exhibited a gelation temperature of 30-35 °C, indicating its suitability for situ gel formation in the colon. The 1H NMR analysis confirmed minimal interactions between 5-ASA and the polymers. Increasing the CP concentration markedly delayed drug release, likely due to enhanced network entanglement within the gel. Ex vivo evaluation using porcine colonic mucosa indicated reduced leakage and improved adhesion compared with a commercial formulation. Furthermore, in vitro studies using Caco-2 cells showed enhanced retention of the active compounds. These findings indicate that the proposed system enables injectable administration, in situ gelation, strong mucosal adhesion, and gradual release of 5-ASA while maintaining enhanced mucoadhesion and rectal retention, thereby improving retention and therapeutic potential. Furthermore, the administration of the formulation to rats with UC led to a significantly higher anti-inflammatory effect. Thus, the developed approach represents a promising strategy for enhancing treatment efficacy and patient compliance in ulcerative colitis.