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

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 1; p. 55
• Main Authors: Santos, Filipa, P S Leitão, Maria Inês, C Duarte, Ana Rita
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-12-2018; MDPI
• Subjects: Antiinfectives and antibacterials; Arginine; Arginine - chemistry; Arginine - pharmacology; Arginine - therapeutic use; Bioavailability; Caco-2 Cells; Calorimetry; Calorimetry, Differential Scanning; Carbon-13 Magnetic Resonance Spectroscopy; Cell Survival - drug effects; Cell viability; Citric acid; Cytotoxicity; Differential scanning calorimetry; Diffusion; Drug resistance; Drugs; Ethambutol; Ethambutol - chemistry; Ethambutol - pharmacology; Ethambutol - therapeutic use; Eutectics; HIV; Human immunodeficiency virus; Humans; Hydrogen; Infections; Inhibitory Concentration 50; l-arginine; Light microscopy; Magnetic resonance spectroscopy; Microscopy; Mortality; Nitric oxide; NMR; NMR spectroscopy; Nuclear magnetic resonance; Optical microscopy; Permeability; Phase transitions; Proton Magnetic Resonance Spectroscopy; Solubility; Solvents; Solvents - chemistry; therapeutic deep eutectic solvents; Tuberculosis; Tuberculosis - drug therapy; therapeutic deep eutectic solvents; l-arginine; ethambutol; tuberculosis
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24010055

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
C-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.