In vitro and in vivo evaluation of biotin-mediated PEGylated nanostructured lipid as carrier of disulfiram coupled with copper ion

Abstract Disulfiram loaded biotin-polyethylene glycol 2000- distearyl phosphatidyl ethanolamine modified nanostructured lipid carriers were generated so as to increase the long-circulation time, enhance encapsulation efficiency, loading capacity and improve targeting ability. The optimized composition of disulfiram loaded biotin-polyethylene glycol 2000- distearyl phosphatidyl ethanolamine modified nanostructured lipid carriers was selected using central composite design, showing a spherical shape of 103 ± 3 nm in particle size as well as loading capacity of 4.72 ± 0.89 and encapsulation efficiency of 89.87 ± 0.42. The noncrystalline state of disulfiram was recognized by differential scanning calorimetry. The in vitro release study demonstrated the burst drug release in the beginning and afterwards a sustained release. The cytotoxicity assay exhibited stronger lethal effect towards breast cancer 4T1 cells in company with copper ion. The in vivo study showed the disulfiram loaded biotin-polyethylene glycol 2000- distearyl phosphatidyl ethanolamine modified nanostructured lipid carriers coupled with copper ion were accumulated extensively over time in the tumor through Near Infrared Ray fluorescence imaging study and inhibited tumor growth effectively in the tumor models in breast cancer mice. In our study, biotin-polyethylene glycol 2000- distearyl phosphatidyl ethanolamine modified nanostructured lipid carriers were stable and efficient for disulfiram delivery.