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 +/- 2.07 nm with a narrow size distribution of 0.217 +/- 0.035 and zeta potential around -22.30 +/- 2.11 mV, respectively. The highest drug loading and entrapment efficiency achieved was 5.516 +/- 1.98%, and 91.61 +/- 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.