Zinc diethyldithiocarbamate (Zn (DDC)₂), a disulfiram metabolite (anti-alcoholism drug), has shown a strong anti-cancer activity in vitro. However, its application was limited by its low aqueous solubility and rapid metabolism. In this study, the solubility enhancement of Zn (DDC)₂ is investigated by forming inclusion complexes with cyclodextrins. The inclusion complexes were prepared using two different types of beta-cyclodextrins, SBE-CD and HP-CD. Phase solubility diagrams for the resulting solutions were assessed; subsequently, the solutions were freeze-dried for further characterisation studies using DSC, TGA, XRD, and FTIR. The cytotoxic activity of the produced inclusion complexes was evaluated on human lung carcinoma cells using the MTT assay. The solubility of Zn (DDC)₂ increased significantly upon adding beta-cyclodextrins, reaching approximately 4 mg/mL for 20% w/w CD solutions. The phase solubility diagram of Zn (DDC)₂ was of the Ap-type according to the Higuchi and Connors model. Characterisation studies confirmed the inclusion of the amorphous drug in the CD-Zn (DDC)₂ complexes. The cytotoxicity of Zn (DDC)₂ was enhanced 10-fold by the inclusion complexes compared to the free drug. Overall, the resulting CD-Zn (DDC)₂ inclusion complexes have a potential for treatment against lung cancer.

Disulfiram (DS) has been shown to have potent anti-cancer activity; however, it is also characterised by its low water solubility and rapid metabolism in vivo. Biodegradable polylactic-co-glycolic acid (PLGA) polymers have been frequently employed in the manufacturing of PLGA nano-carrier drug delivery systems. Thus, to develop DS-loaded PLGA nanoparticles (NPs) capable of overcoming DS’s limitations, two methodologies were used to formulate the NPs: direct nanoprecipitation (DNP) and single emulsion/solvent evaporation (SE), followed by particle size reduction. The DNP method was demonstrated to produce NPs of superior characteristics in terms of size (151.3 nm), PDI (0.083), charge (−37.9 mV), and loading efficiency (65.3%). Consequently, NPs consisting of PLGA and encapsulated DS coated with mPEG_2k-PLGA at adjustable ratios were prepared using the DNP method. Formulations were then characterised, and their stability in horse serum was assessed. Results revealed the PEGylated DS-loaded PLGA nano-carriers to be more efficient; hence, in-vitro studies testing these formulations were subsequently performed using two distinct breast cancer cell lines, showing great potential to significantly enhance cancer therapy.

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 (A_L 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.

(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.

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.