Drug-delivery oriented solubility enhancement of curcumin in choline chloride-based acidic deep eutectic solvents: thermodynamic analysis and MCF-7 cytotoxicity assessment.

Curcumin is a bioactive compound with well-established chemopreventive and anticancer properties, but its pharmaceutical application is limited by extremely low aqueous solubility and poor formulation-dependent bioavailability. In this study, three choline chloride-based acidic deep eutectic solvents (ADESs), namely choline chloride/propionic acid (ChCl/Pro), choline chloride/acetic acid (ChCl/Ace), and choline chloride/lactic acid (ChCl/Lac), were systematically evaluated as solubilizing media for curcumin. The mole fraction solubility of curcumin was determined in aqueous ADES mixtures over 298.15-313.15 K at different ADES mass fractions. In all systems, solubility increased with both temperature and ADES content, and the overall solubilization efficiency followed the order ChCl/Pro > ChCl/Ace > ChCl/Lac. The highest solubility was obtained in neat ChCl/Pro at 313.15 K, where the mole fraction solubility reached 2.237 × 10-2, corresponding to an enhancement of more than 100,000-fold relative to water. The experimental data were correlated using the Jouyban-Acree, e-NRTL, and UNIQUAC models, with the Jouyban-Acree model showing the best overall performance. Thermodynamic analysis based on van't Hoff and Gibbs equations indicated that curcumin dissolution in the ADES-containing media is endothermic and predominantly enthalpy-driven. In vitro MTT assays on MCF-7 human breast cancer cells showed concentration-dependent cytotoxicity for the curcumin-loaded ADES systems, with IC50 values of 0.34 ± 0.01, 0.37 ± 0.01, and 0.42 ± 0.02 mg L-1 for ChCl/Lac, ChCl/Pro, and ChCl/Ace, respectively. Overall, choline chloride-based acidic DESs, particularly ChCl/Pro, markedly improve the solubility of curcumin and provide a promising solubilizing media for curcumin that may serve as a basis for further pharmaceutical formulation development.