Preparation and Characterization of Disulfiram and Beta Cyclodextrin Inclusion Complexes for Potential Application in the Treatment of SARS-CoV-2 via Nebulization

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 17; p. 5600
• Main Authors: Pereira, Ana Maria, Kaya, Ayse, Alves, Dan, Ansari-Fard, Niusha, Tolaymat, Ibrahim, Arafat, Basel, Najlah, Mohammad
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 31.08.2022; MDPI
• Subjects: Alcoholism; Antiviral activity; Antiviral agents; Aqueous solutions; Calorimetry; Care and treatment; Coronaviruses; COVID-19 vaccines; Cyclodextrins; Differential scanning calorimetry; Disease transmission; Disulfiram; Drugs; FDA approval; Fourier analysis; Fourier transforms; Genomes; Health aspects; Inclusion complexes; Infrared analysis; Infrared spectroscopy; Inhalation; Linear functions; Metabolism; Middle East respiratory syndrome; nebulization; Pandemics; Pharmaceutical industry; Respiration; Respiratory diseases; Respiratory tract diseases; SARS-CoV-19; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Solubility; Thermogravimetric analysis; β-Cyclodextrin; United Kingdom
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27175600

Disulfiram (DS), known as an anti-alcoholism drug, has shown a potent antiviral activity. Still, the potential clinical application of DS is limited by its low water solubility and rapid metabolism. Cyclodextrins (CDs) have been widely used to improve the solubility of drugs in water. In this study, five concentrations of hydroxypropyl β-cyclodextrin (HP) and sulfobutyl ether β-cyclodextrin (SBE) were used to form inclusion complexes of DS for enhanced solubility. Solutions were freeze-dried, and the interaction between DS and CD was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the nebulization properties of the DS–CD solutions were studied. The aqueous solubility of DS increased significantly when loaded to either of both CDs. The phase solubility of both complexes was a linear function of the CD concentration (AL type). Furthermore, physicochemical characterization studies showed a potent inclusion of the drug in the CD–DS complexes. Aerosolization studies demonstrated that these formulations are suitable for inhalation. Overall, the CD inclusion complexes have great potential for the enhancement of DS solubility. However, further studies are needed to assess the efficacy of DS–CD inclusion complexes against SARS-CoV-2 via nebulization.