pH-Sensitive Chitosan-Based Hydrogels Trap Poloxamer Micelles as a Dual-Encapsulating Responsive System for the Loading and Delivery of Curcumin.

pH-sensitive hydrogels are important soft biomaterials as they mimic biological organisms by altering their properties in response to small pH changes in biological fluids. In this work, novel chitosan (Cs) hydrogels were developed using an innovative dual curcumin (Cur) encapsulation system. Cur was loaded into poloxamer 407 micelles and incorporated into citric acid (CA) cross-linked Cs hydrogels using a central composite design. The hydrogels were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), rheological tests, and in vitro experiments, such as hemolysis and cytotoxicity assays. FTIR confirmed cross-linking between Cs and CA, while DSC suggested interactions between Cur-loaded micelles and the hydrogel matrix. Rheological analysis revealed gel-like behavior, with G' consistently higher than G, and temperature influenced hydrogel properties. SEM showed a denser network when Cur-loaded micelles were incorporated, slowing Cur release. At physiological pH (7.4), 75% of Cur was released after 7 days, while 84% was released at pH 5.5, showing pH-responsive behavior. Cytotoxicity tests showed over 80% viability of VERO CCL-81 cells (0.2-20 ppm hydrogel). This dual-encapsulation system provides a simple and effective platform for loading lipophilic drugs into pH-responsive hydrogels.