Doxorubicin & Disulfiram-metabolite Loaded Nanocarriers for The Effective Combination Therapy Against Acute Myeloid Leukaemia

Abstract

Leukaemia is a hematopoietic system malignancy depicted by the infiltration of the bone marrow, blood & other tissues by proliferative, and abnormally differentiated cells of the hematopoietic system. The available therapies aim to induce cell death of these poorly differentiated cells by various means. Anthracyclines (doxorubicin) regime remains the standard first-line treatment for leukaemia. Doxorubicin (DOX) has a potent anticancer activity at higher dosage concentration which imparts cardiac, renal, and hepatic toxicity. Disulfiram metabolite complex, zinc diethyldithiocarbamate (Zn-DDC), has a potent anticancer efficacy, however, it has short half-life primarily attributed to its instability in gastric juice and the blood stream. The current study employed a "thin film hydration method" to synthesize liposomal nanoparticles encapsulating doxorubicin (DOX-NPs), Zn-DDC (Zn-DDC-NPs), and both Zn-DDC and DOX (Zn-DDC+DOX-NPs). In-vitro 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, and morphological, and histological examination were conducted to evaluate treatment approaches. All liposomal formulations overcome their limitation, improved the blood parameters (p>0.05), restored the hepatic, and renal enzyme levels (p>0.05), and reduced the blast cells in blood and tissues. However, in coencapsulated liposomes Zn-DDC reduce the cytotoxicity caused by doxorubicin and provide results more analogous to normal