Doxorubicin Supplemented with Pravastatin in Lipid Nanoemulsion Induces Antineoplastic Activity with Limited Hepatotoxicity and Cardiotoxicity in Tumor-Bearing Mice


Affiliations

  • King Abdulaziz University, Regenerative Medicine, Unit King Fahd Center for Medical Research, Jeddah, Saudi Arabia
  • King Abdulaziz University, Department of Pharmacology, Faculty of Medicine, Jeddah, Saudi Arabia
  • King Abdulaziz University, Department of Biochemistry, Faculty of Science, Jeddah, Saudi Arabia
  • King Abdulaziz University, Department of Biology, Faculty of Science, Jeddah, Saudi Arabia
  • Ain Shams University, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo, 11566, Egypt

Abstract

Doxorubicin (DXR) is widely indicated as anticancer drug, but serious cardiotoxicity limits its clinical application. Recently, Pravastatin (PS) is one of the statins that appear to possess a potential role in cancer therapy despite its hepatotoxicity. Interestingly, drug delivery systems are designed for targeted and controlled delivery of one or more drugs loaded in nanoparticles, holding an enormous potential in therapeutics. Therefore, the aim of the current study was to assess the tolerability of a novel nanoemulsion formulation holding DXR and pravastatin (DXR+PS/LNE) in Swiss albino mice bearing Ehrlich Ascites Carcinoma (EAC). The efficacy and tolerability of nanoemulsion formulation was assessed by monitoring body weight changes, biochemical and histopathological profiles of cardiac and hepatic tissues. The formulated DXR+PS/ LNE has mean droplet diameter of 139.90±3.85 nm. The present findings indicated that DXR+PS/LNE caused a significant decrease in body weight change and a 217.35 % increase in the mean survival time compared to EAC-challenged mice. In addition, no significant changes in biochemical parameters were detected compared to corresponding controls. The current preclinical results suggest that the nanoemulsion formulation of doxorubicin with pravastatin could be a promising novel cancer therapy, in terms of tolerability.


Keywords

Cardiac Tissue, Ehrlich Ascites Carcinoma, Hepatic Tissue, Mean Survival Time, Statins, Transmission Electron Microscope

Subject Discipline

Science-Biochemistry-Nanomedicine

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