Exploring Drug Repositioning: Enhanced Co-Delivery of Disulfiram and Celecoxib by Nanostructured Lipid Carriers for Breast Cancer Cells

Background: In the current era, the importance of pharmaceutical technology and research in innovating novel drugs and formulations is undeniable. Objective: This study aimed to produce a nanoscale drug delivery system for the simultaneous delivery of repurposed disulfiram (DSF) and celecoxib (CXB). Methods: The co-formulation was prepared utilizing the emulsification ultrasonication technique to enhance the anti-cancer activity through NLCs. The surface morphology of the optimized NLCs was examined using TEM, while physicochemical characterization analyses employed FTIR, DSC, PXRD, and TGA. In-vitro cell uptake studies were conducted through MTT assay, confocal microscopy, and flow cytometry, respectively. Results: The optimized DSF-CXB NLCs demonstrated a mean particle size of 144.2 nm, with a drug loading of 9.8% for DSF and 9.87% for CXB. The re-dispersibility index was measured at 103.26%, indicating effective dispersion. Stability analysis over 30 days confirmed the formulation's high stability. Transmission electron microscopy revealed spherical-shaped nanoparticles. Fourier transform infrared spectroscopy indicated no interaction between excipients and the formulation. Both DSC and PXRD techniques affirmed complete encapsulation of both drugs in the NLCs. In-vitro cytotoxicity of DSF-CXB NLCs exhibited a concentration-dependent increase compared to free DSF and CXB solutions in breast cancer cells. Confocal microscopy and flow cytometry studies demonstrated time-dependent internalization of the optimized formulation in 4T1 cancer cells. Conclusion: These results suggest that repurposing DSF and CXB NLCs holds promise as a co-delivery system for various cancers, potentially leading to improved therapeutic outcomes.