Doxorubicin loaded zinc oxide nanoflowers – Surmounting drug-induced toxicity

Abstract

Doxorubicin (DOX) induces cardiotoxicity, hepatotoxicity and nephrotoxicity, through multiplicity of mechanisms involving the production of free radicals causing oxidative stress and apoptosis. Zinc oxide (ZnO) nanomaterials, besides biocompatibility and biodegradability, also show the protective effect on cells and organs. The current study aspires to delve into the protective effects of ZnO in DOX-loaded ZnO nanoflowers (DOX-ZnO-NFs). Comparative in-vitro toxicities of DOX, blank zinc oxide nanoflowers (ZnO-NFs) and DOX-ZnO-NFs were examined against in-vitro normal Henrietta Lacks (HeLa) cell line and in-vivo in the Wistar rats. The change in body weight, hematological parameters and biochemical biomarkers of heart, kidney and liver and histopathology of tissues were examined at 24 h and after 14 days post dosing of the test moieties. DOX-ZnO-NFs portrayed biocompatibility and safety in the HeLa cells and the kidneys, liver and heart of Wistar rats. At 30 μg/ml, DOX-ZnO-NFs showed 72.53 ± 0.39% cell survival rate, relative to 80.59 ± 0.99% by ZnO-NFs and 13.8 ± 0.22%, by DOX. DOX-ZnO-NFs and ZnO-NFs caused slight change in organ's weight, minimum haemolysis, little effect on liver and kidney enzymes, improved activity of antioxidant enzymes and maintained tissues' architecture relative to the bare DOX. The drug-free ZnO-NFs with the maximum safety supported the protective effect of ZnO and, thus DOX-ZnO-NFs surmounted the DOX-induced systemic toxicity.