Properties of Therapeutic Deep Eutectic Solvents of l-Arginine and Ethambutol for Tuberculosis Treatment

Abstract

The treatment for tuberculosis infection usually involves a prolonged regimen of multiple antibacterial drugs, which might lead to various secondary effects. For preventing drug resistance and side-effects of anti-tuberculosis drugs, new methods for improving the bioavailability of APIs were investigated. The strategy proposed consists of the preparation of therapeutic deep eutectic solvents (THEDES), that incorporate l-arginine and ethambutol. The eutectic mixtures were prepared by mixing the components at a certain molar ratio, until a clear liquid solution was formed. The prepared mixtures were characterized by differential scanning calorimetry (DSC), polarized optical microscopy (POM) and nuclear magnetic resonance spectroscopy (1H and 13C-NMR). The solubility and permeability of the drugs when they are in the THEDES form was evaluated at 37 °C, in phosphate buffered saline (PBS). Solubility studies showed an increase of the solubility of ethambutol when incorporated in the eutectic system. The cytotoxicity was evaluated using a model cell line (Caco-2), comparing the cytotoxicity of the API incorporated in the eutectic system. We observed that the cell viability in the THEDES was affected by the presence of citric acid, and higher cytotoxicity values were observed. Nonetheless, these findings do not compromise the possibility to use these systems as new delivery systems for ethambutol and arginine.

Polymer Science and Engineering Using Deep Eutectic Solvents

“…By definition, THEDES are deep eutectic solvents for which at least one of the mixture components is an active pharmaceutical ingredient [125]. However, bioactive compounds solubilized in DES are also commonly considered as THEDES [126].…”

Unravelling the nature of citric acid:l-arginine:water mixtures: the bifunctional role of water

“…While these studies are all based on choline chloride-based DES, they highlight the importance of characterizing the water influence on other DES, opening the possibility to include water in the DES preparation as a starting material rather than a solvent. Recently, mixtures of citric acid:L-arginine:water of mole ratios 1:1:4, 1:1:5, 1:1:6, 1:1:7, 2:1:7, 2:1:8, 2:1:9 were reported as new DES 15,16 , given their low water amounts, between 15 to 25 weight percent. Although the authors named these mixtures as DES, given the complexity of these systems and the presence of water, other possibilities may be considered.…”

Therapeutic Role of Deep Eutectic Solvents Based on Menthol and Saturated Fatty Acids on Wound Healing

“… 14 − 17 In biomedical applications, DES can be used to improve solubility, permeation, and absorption of active pharmaceutical ingredients (APIs). 18 − 22 The APIs can be used as a DES counterpart, being hence called therapeutic deep eutectic systems (THEDES). 6 , 19 , 23 Herein, insights on therapeutic effects of the THEDES based on menthol and different saturated fatty acids will be addressed.…”