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.

Disulfiram (DS) has an excellent anti-viral activity; however, its low water-solubility and first-pass metabolism are limiting its clinical applications. Cyclodextrins (CDs) have been used as solubility enhancers and carriers of DS proposed for inhalation to treat SARS-CoV-19. Two types of CDs (hydroxypropyl β-cyclodextrin and sulfobutyl ether β-cyclodextrin) were used to form inclusion complexes with DS, and drug solubility was assessed using spectrophotometric analytical method. Formulations were freeze-dried and characterized using DSC, TGA and FTIR. Nebulization technique was used to assess the potential for generating aerosols. All inclusion complexes are proved to be suitable for inhalation, therefore, potentially effective therapy for further investigation against SARS-CoV-19 is shown. 

Diethyldithiocarbamate zinc (Zn(DDC)2), has shown promising antineoplastic effects against a wide variety of cancers. However, this application was hindered by its poor water solubility. Therefore, complexation with cyclodextrin was used to enhance the solubility. Five different concentrations of 2-hydroxyl beta-cyclodextrin (HP) and ether beta-cyclodextrin (SBE) were used. CD-Zn(DDC)2 solutions were freez-dried for further characterisation using DSC, TGA and FT-IR. The phase solubility study showed a significant water-solubility enchantment of  Zn(DDC)2, and the characterisation studies confirmed the formation of inclusion complexes CD-Zn(DDC)2. Overall, CDs have improved Zn(DDC)2 solubility significantly and showed a promising anticancer activity against lung cancer cells. Hence, CD-Zn(DDC)2 complexes have a great potential for further studies against cancer.    

(DDC)2Zn, disulfiram (DS) metabolite, has shown promisinganticancer effects in vitro but further investigations in vivo are limited by itspoor water solubility. In this study, liposomes are assessed as a deliverysystem for (DDC)2Zn. Liposomes were prepared by the thin-filmhydration method, followed by high-pressure homogenisation (HPH) for sizereduction. The nano-liposomes were then characterised by size, polydispersityindex (PDI), zeta potential (ZP), drug loading and encapsulation efficiencies(DLE% and EE%), and MTT cytotoxicity assay. The HSPC-based (PBS) liposomesshowed a nano-range of sizes (< 200nm), good PDI (<0.5) but moderate EE%(<40%). However, (DDC)2Zn liposomal formulations showed enhanced cytotoxicactivities toward colorectal cancer cells. Therefore, liposomal formulations of(DDC)2Zn with improved DLE% and EE% might have immense potential incancer therapy.