Globular protein stabilized nanoparticles for delivery of disulfiram: fabrication, characterization, in vitro toxicity, and cellular uptake

Abstract

Disulfiram (DSF), an FDA-approved anti-alcoholic drug, has recently shown that it possesses anti-cancer effects. However, DSF is hydrophobic in nature with less stability. Therefore, new approaches are required for the effective delivery of DSF to treat cancers. Herein, we prepared DSF loaded soy protein isolate (SPI) nanosuspension (Ns) for enhancing the anti-cancer delivery of DSF. The optimized DSF-SPI-Ns had an average particle size of 164.28 AE 2.07 nm with a narrow size distribution of 0.217 AE 0.035 and zeta potential around À22.30 AE 2.11 mV, respectively. The highest drug loading and entrapment efficiency achieved was 5.516 AE 1.98%, and 91.61 AE 1.15%, respectively. The surface morphology of Ns was revealed by TEM, and the FTIR DSC, PXRD, and TGA were used for physicochemical characterization. Further, fluorescence spectroscopy and molecular docking studies were carried out to understand the interactions between (SPI and DSF) and binding sites of DSF on the surface of SPI, respectively. In vitro release studies showed a sustained release pattern and followed a Fickian diffusion release from the Ns. The in vitro cytotoxicity of SPI indicated the excellent biocompatibility, and DSF-SPI-Ns were found to be more cytotoxic compared to the free DSF solution. Moreover, the cellular uptake studies also indicated the effective delivery of the formulation to the cancer cells. Results of the current study suggested that the SPI coated Ns might be a promising drug delivery system for hydrophobic DSF, and the potential application of SPI as a coating/stabilizing agent for the delivery of hydrophobic/hydrophilic cancer therapeutics.

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

“…The sample of the free drug had a significant decrease in mass within the range of 160 °C to 220 °C as a result of a fast decomposition rate [ 31 ]. Both pure CDs experienced different behaviors.…”

“…Nonetheless, some of the most characteristic peaks of DS described above (C-C, C=S, CH 2 , CH 3 , and N-C=S) were still slightly detected in the freeze-dried formulations (1200 cm −1 , 1270 cm −1 , 1420 cm −1 , and 1491 cm −1 for HP20; 1270 cm −1 , 1351 cm −1 , 1417 cm −1 , and 1514 cm −1 for SBE20). This indicates that the chemical structure of the drug did not change during the preparation of the complexes [ 31 ]. Furthermore, the fact that Suliman et al did not significantly report the DDC-Cu characteristic peaks with the same CDs might be due to the lower solubility achieved for DDC-Cu (4 mg/mL) [ 29 ].…”

In Vitro Evaluation of Photodynamic Activity of Plant Extracts from Senna Species against Microorganisms of Medical and Dental Interest

“…In order to overcome these challenges confers by Gram-negative cell wall and the extracellular matrix, organic and inorganic nanoparticles have been widely used [ 40 , 41 , 42 , 43 , 44 ]. In a previous systematic review and meta-analysis, the use of inorganic nanoparticles was employed as a drug delivery system facilitating the PS uptake in microbial cells and improving the effect of aPDT [ 44 ].…”

“…In a previous systematic review and meta-analysis, the use of inorganic nanoparticles was employed as a drug delivery system facilitating the PS uptake in microbial cells and improving the effect of aPDT [ 44 ]. In addition, nanoparticles improve the bioavailable, solubility, selectivity and can be used to overtake the cytotoxicity effect related to possible new drugs and PS [ 40 , 41 , 42 , 43 ]. Besides that, antimicrobial peptides can be also utilized in combination with aPDT [ 45 ] to overcome these microbial challenge citated above.…”

Microfluidic Encapsulation of Vorinostat in Calcium Alginate Microparticles: Prolonged Release and Enhanced in vitro Cytotoxicity

“…The in vitro release of vorinostat from the alginate microparticles was investigated using the dialysis method, as described in previous studies. [29][30][31] A suspension of 20 milligrams of alginate microparticles loaded with vorinostat was prepared in 2 mL of phosphate buffer saline (PBS) with a pH of 7.4. This suspension was then transferred into dialysis bags with a molecular weight cutoff of 12000-14000 Da (Edulab, UK) and sealed at the ends.…”