Doxorubicin and disulfiram metabolite encapsulated biomimetic liposomal formulation as an effective combination therapy against leukaemia

Leukaemia is a haematopoietic system malignancy depicted by the infiltration of the bone marrow, blood and other tissues by proliferative and abnormally differentiated cells of the haematopoietic system. The available therapies aim to induce cell death of these poorly differentiated cells by various means. The anthracycline doxorubicin (DOX) regime remains the standard first-line treatment for leukaemia. DOX has potent anticancer activity at higher dosage concentration and imparts cardiac, renal and hepatic toxicity. The disulfiram metabolite complex zinc diethyldithiocarbamate (Zn-DDC) has potent anticancer efficacy; however, it has a short half-life due to its instability in gastric juice and the blood stream. The present study employed a thin-film hydration method to synthesise liposomal nanoparticles encapsulating DOX (DOX-NPs), Zn-DDC (Zn-DDC-NPs) and both Zn-DDC and DOX (Zn-DDC + DOX-NPs).<i>In vitro</i>cytotoxicity and antioxidant assays were performed to assess their cytotoxicity and antioxidant activity. The liposomes were evaluated against leukaemia in Wistar rats. After leukaemia induction through benzene, haematological and serological assays, morphological and histological examinations were conducted to evaluate treatment approaches. All liposomal formulations overcame their limitations, improved the blood parameters (<i>p</i>> 0.05), restored the hepatic and renal enzyme levels (<i>p</i>> 0.05), and reduced the blast cells in blood and tissues. However, in co-encapsulated liposomes, Zn-DDC reduced the cytotoxicity caused by DOX and provided results more analogous to normal.