An integrated green strategy for enhanced aqueous solubility and loading of curcumin: Pressurized hot water meets cyclodextrin complexation.

This study introduces an integrated, green solubilization strategy by combining pressurized hot water (PHW) treatment with β-cyclodextrin (βCD) complexation to enhance the aqueous solubility and formulation performance of curcumin (Cur). Cur was subjected to three solubilization protocols: PHW processing, βCD complexation, and a novel two-step PHW-Cur/βCD method. Comparative evaluation revealed that the PHW-Cur/βCD complex achieved the highest solubility (0.163 mg.mL-1), representing a ~7.4-fold increase in loading capacity and >95% encapsulation efficiency, outperforming both individual techniques. Physicochemical characterization (DLS, TGA, DSC, XRD, FESEM, FTIR, and 1H NMR) confirmed the formation of inclusion complexes, with particle size (~196 nm), low polydispersity index, and enhanced thermal stability. Furthermore, molecular dynamics simulations provided atomistic insight into the interaction mechanisms and suggested stronger host-guest interaction and favorable diffusion behavior under PHW conditions. Radial distribution function analyses showed possible enhanced hydration shells and increased hydrogen bonding in the PHW Cur/βCD system. These findings suggest the potential of this environmentally friendly dual modality strategy for enhancing both the aqueous solubility and loading performance of poorly water soluble compounds, with prospective applications in pharmaceutical delivery systems and functional food formulations.