Natural Deep Eutectic Solvent-Based Eutectogels for Enhanced Colon-Targeted Delivery of Mesalazine

Poor solubility and low permeability remain major obstacles to the oral bioavailability of mesalazine (5-aminosalicylic acid, 5-ASA), a BCS Class IV anti-inflammatory drug used in the treatment of inflammatory bowel diseases. In this study, we report a novel eutectogel (EG) platform based on a natural deep eutectic solvent (NADES) composed of choline chloride and lactic acid (ChCl:LA, 1:10 molar ratio). The NADES significantly enhanced mesalazine solubility, reaching 35 mg/mL, nearly 40-fold higher than in water. The drug-loaded NADES was structured using hydroxyethyl cellulose and Carbomer 140 to obtain a gel matrix, which was subsequently coated with Eudragit® S100 to provide pH-dependent release and gastro-resistance. Physicochemical characterization was carried out via FT-IR and NMR spectroscopy, polarized optical microscopy (POM), and swelling studies in simulated fluids. In vitro release studies under simulated gastrointestinal conditions revealed minimal drug release at gastric pH (1.2) and a sustained release (>80%) at colonic pH (7.4) over 48 h. These results support the potential of ChCl:LA-based eutectogels as a biocompatible, green, and effective delivery system for the site-specific release of poorly soluble drugs in the colon.