Abstract
Disulfiram (DSF) has been considered as “Repurposing drug” in cancer therapy in recent years based on its good antitumor efficacy. DSF is traditionally used as an oral drug in the treatment of alcoholism. To overcome its rapid degradation and instability, DSF nanosuspensions (DSF/SPC-NSps) were prepared using soybean lecithin (SPC) as a stabilizer of high drug-loaded content (44.36 ± 1.09%). Comprehensive characterization of the nanosuspensions was performed, and cell cytotoxicity, in vivo antitumor efficacy and biodistribution were studied. DSF/SPC-NSps, having a spherical appearance with particle size of 155 nm, could remain very stable in different physiological media, and sustained release. The in vitro MTT assay indicated that the cytotoxicity of DSF/SPC-NSps was enhanced remarkably compared to free DSF against the 4T1 cell line. The IC50 value decreased by 11-fold (1.23 vs. 13.93 μg/mL, p < 0.01). DSF/SPC-NSps groups administered via intravenous injections exhibited better antitumor efficacy compared to the commercial paclitaxel injection (PTX injection) and had a dose-dependent effect in vivo. Notably, DSF/SPC-NSps exhibited similar antitumor activity following oral administration as PTX administration via injection into a vein. These results suggest that the prepared nanosuspensions can be used as a stable delivery vehicle for disulfiram, which has potential application in breast cancer chemotherapy.
Highlights
Disulfiram (DSF, Antabus, Fig. 1) is a Food and Drug Administration (FDA) approved anti-alcoholic drug since the 1940s [1, 2]
DLS measurement revealed that the particle size of DSF/soybean lecithin (SPC)-NSps was decreased and the drug-loading content was increased with the change in the drug/carrier ratio from 1:2 to 1:1 (Table 1)
transmission electron microscopy (TEM) observation revealed that DSF/SPC-NSps were spherical and evenly distributed (Fig. 2b)
Summary
Disulfiram (DSF, Antabus, Fig. 1) is a Food and Drug Administration (FDA) approved anti-alcoholic drug since the 1940s [1, 2]. Recent researches demonstrated that DSF exhibited strong anticancer activity toward various tumor types, including breast carcinoma, liver carcinoma, colorectal cancer, non-small cell lung cancer and glioblastoma carcinoma [3,4,5,6,7,8,9]. The higher copper-chelated DSF concentrations in tumor cells enable DSF to target cancer instead of normal tissues [24]. These studies demonstrate that DSF may be used as a potent anticancer agent in clinics due to its high activity and safety
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