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

Abstract

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.

Tenofovir antiviral drug solubility enhancement with β-cyclodextrin inclusion complex and in silico study of potential inhibitor against SARS-CoV-2 main protease (Mpro)

“…Additionally, the PatchDock and FireDock servers were used to research the protein and small molecule interactions of the β-CD:TFR inclusion complex with SARS-CoV-2 (M Pro ) protease inhibitors [52] , [53] , [54] , [55] , [56] . The results are shown in Fig.…”

Evaluation on the inclusion behavior of β-cyclodextrins with lycorine and its hydrochloride

“…The thermal properties of all inclusion complexes were analyzed by TG [50] . The results of mass changes of all inclusion complexes were different from β-CDs, Lyc, Lyc∙HCl and their corresponding physical mixtures, as presented in Fig.…”

Preparation and Characterisation of Zinc Diethyldithiocarbamate–Cyclodextrin Inclusion Complexes for Potential Lung Cancer Treatment

“…For the Zn (DDC) 2 complexes, the deviation increased as the concentration increased for both CDs. Therefore, cyclodextrins formed complex aggregates that are capable of solubilizing additional amounts of Zn (DDC) 2 through non-inclusion complex formations or the formation of micelle-like structures [ 23 , 34 ]. Similar findings for Cu (DDC) 2 were reported by Suliman et al [ 5 ], in which the phase solubility diagram of Cu (DDC) 2 had a non-linear relationship when forming inclusion complexes with CDs.…”

“…CDs consist of a lipophilic inner cavity with a hydrophilic exterior surface; due to their truncated cone structure, they possess substantial capabilities to form inclusion complexes in both aqueous solutions and the solid compound state [ 20 , 21 ]. Inclusion complexes are formed by binding forces, such as hydrogen bonds and hydrophobic and van der Waals interactions [ 22 , 23 ]. There are two main factors for forming inclusion complexes: the first is the suitability of CD size for the drug molecule and the second is the optimisation of the thermodynamic interactions between the complex components (CDs, the drug, and the solvent) [ 22 ].…”

“…The resulting CD–drug inclusion complexes have improved aqueous solubility with increased bioavailability and shelf-life of the host (drug) [ 24 , 25 ]. CDs have the ability to enhance the aqueous solubility of many lipophilic drugs without altering their permeation properties through lipophilic membranes, which make them a more prominent pharmaceutical excipient [ 23 ]. Inclusion complexes of cyclodextrins with DS developed to enhance its solubility for the treatment of cataracts and SARS-CoV-2 have been reported [ 26 , 27 ].…”