A Novel Floating In Situ Chewable Gel System for Curcumin Delivery with Potential Application in Obesity Management

Curcumin exhibits potent anti-obesity and anti-inflammatory activities; however, its therapeutic application is limited by poor aqueous solubility and low oral bioavailability. A curcumin-loaded chewable gel was developed to transform into an in situ gastric gel upon contact with gastric fluid after mastication. Curcumin solid dispersions (CUR-SDs) were prepared with Eudragit^® EPO (1:1-1:7, w/w) using the solvent evaporation method. The optimized formulation (1:3) markedly enhanced solubility and dissolution in acidic medium (0.1 N HCl, pH 1.2) compared with crystalline curcumin and physical mixtures. The optimized CUR-SD was subsequently incorporated into chewable gels composed of sodium alginate and κ-carrageenan, with calcium carbonate as a gas-forming agent. The formulations formed buoyant matrices under acidic conditions, exhibiting floating lag times of 21-215 s and sustaining drug release for up to 8 h. Increasing polymer content improved mechanical strength and modulated release kinetics. Among the tested formulations, F7 achieved the optimal balance between texture properties, floating behavior, and controlled-release performance. In LPS-stimulated RAW264.7 macrophages, curcumin, CUR-SD, and F7 showed comparable and potent anti-inflammatory activity (IC₅₀ = 4.12-4.84 µg/mL), outperforming indomethacin. In 3T3-L1 adipocytes, F7 significantly reduced lipid accumulation (~47%) in a concentration-dependent manner. These findings demonstrate that this transformable chewable in situ gelling platform is a promising gastroretentive strategy for improving the oral therapeutic efficacy of poorly soluble bioactive compounds for anti-obesity applications.