In recent years, deep eutectic solvents (DESs) have emerged as sustainable alternatives to ionic liquids mainly due to their lower production costs and higher biodegradability/ biocompatibility . DESs are defined as a mixture of organic compounds, interacting by hydrogen bonds, with a melting point significantly lower than that of either the individual components. When based in natural compounds, such as aminoacids, organic acids, sugars or choline derivatives, DES are further defined as natural deep eutectic solvents (NADES), which fully comply with green technology principles. NADESs can be combined with bioactive substances or active pharmaceutical ingredients (APIs) to create therapeutic deep eutectic solvents (THEDES). These present interesting properties for pharmaceutical and biomedical applications because of enhanced solubility, permeation and absorption of APIs.
In this work, we synthetized THEDESs based in choline chloride (ChCl) or menthol, conjugated with three different APIs: acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA).The molar ratios were defined after characterization by differential scanning calorimetry and polarized optical microscopy. The selected THEDESs were used for dissolution studies in PBS for 24 hours and the results obtained have shown a significant increase on the dissolution rate and solubility of the APIs when compared with the API only. This effect was particularly noticeable for the menthol based THEDESs. Antibacterial activity was assessed using E. coli and B. subtillis as gram negative and gram positive model organisms. Results show that all the THEDESs retain the antibacterial activity. Overall, our results suggest the great promise of using THEDESs as solubility enhancers in the development of novel and more effective drug delivery systems.