Solubility improvement of phytochemicals using (natural) deep eutectic solvents and their bioactivity evaluation

Abstract

Plants serve as major sources of bioactive phytochemicals and provide an enormous space for drug discovery. Most of phytochemicals' utilizations are limited by the low water-solubility and thereby low bioavailability. The development of biocompatible solvents with high solvation is a simple and efficient method to improve the solubilities of phytochemicals. In this work, four water-insoluble phytochemicals were chosen as the models to systematically investigate the potential of (natural) deep eutectic solvents ((NA)DESs) as delivery vehicles. After preliminary screening, ten (NA)DESs from sixty prepared (NA)DESs were found to be low viscous and applied to safety evaluation. The cytotoxicity studies revealed that the ten (NA)DESs were safe enough to be used in pharmaceutical and food industry. The solubilities of four model phytochemicals in (NA)DESs were 252–4453 folds higher than those in water. Several solvatochromic parameters were correlated with the solubilities of phytochemicals to tentatively study the solvation between phytochemicals and (NA)DESs. The high solubility could be interpreted by the solute-solvent interactions between phytochemicals and (NA)DESs, such as dipole-dipole interactions and hydrogen bond interactions. The stabilities and bioactivities of phytochemicals dissolved in (NA)DESs were also investigated. It was indicated that not only the stabilities but also the bioactivities were improved by (NA)DESs. The findings of this study show bright application prospect of (NA)DESs as delivery vehicles, which will be of significance for improving the utilization of plant resources.