Effect of water-dimethyl sulfoxide solvents on thermodynamic parameters of complex formation between benzoic acid and 2-hydroxypropyl-β-cyclodextrin

Thermodynamic parameters of complexation between the model drug benzoic acid (BA) and solubilising agent 2-hydroxypropyl-β-cyclodextrin (HPβCD), along with the effects of BA and its complex with HPβCD ([BA⊂HPβCD]) on human serum albumin (HSA), provide essential information for developing new pharmaceutical formulation based on hydrophobic compounds. Thermodynamic parameters (lgK, Δ_rH°, Δ_rG°, TΔ_rS°) of the [BA⊂HPβCD] complex formation were obtained via isothermal titration calorimetry and ¹H NMR experiments in water-dimethyl sulfoxide solvents. The stability of the [BA⊂HPβCD] molecular complex and exothermicity of its formation decrease slightly when using the mixed water-DMSO solvent with a higher content of DMSO in it. The effect of the BA in the free state and in association with HPβCD on the temperature denaturation of HSA in an aqueous dimethyl sulfoxide solution containing 8.0 vol% DMSO was studied by nano-differential scanning fluorimetry. No dependence of HSA denaturation temperature on cyclodextrin concentrations was found. The results confirm that HPβCD does not affect the HSA structure.