Synergistic Antitumor Activity of Doxorubicin and Atorvastatin Combination Loaded Nanoemulsion in Mice

Huda Alkreathy, Mayson Alkhatib, Mona Ali Hadeed Al-thepyani, Khadijah A. Balamash, Sara Alghamdi, Shahid Karim and Aftab Ahmad

Background and Objective: Nanoemulsions (NE) have been proved to enhance the bioavailability of the therapeutic agents with reduced side effects. The objective of the study was to evaluate the antitumor potential of Doxorubicin (Doxo) and Atorvastatin (ATR) combination, either loaded in nanoemulsions (Doxo-ATR-NE) or water (Doxo-ATR-Solution) against ehrlich ascites carcinoma in Swiss albino mice. Materials and Methods: The DOXO and ATR loaded nanoemulsion was prepared by the successive incorporation of different constituents of the nanoemulsion. The nanoemulsion was characterized by Transmission Electron Microscopy (TEM) and further evaluated for the antitumor activity for 15 days experimental study. The antitumor effect of the preparation was assessed by the changes in the body weight, percentage of increased life span (ILS%), mean survival time, serum biochemical parameters for liver and kidney functions, hematological parameters along with the histopathological studies. Results: The ATR-Doxo-NE treated group produce a significant change in body weight as compared with the positive control group and ILS% of mice treated with ATR-Doxo-Sol group was greater than Doxo-Sol group. Interestingly, the ILS% of the ATR-Doxo-NE treated group was higher than the ATR-Doxo-Sol group. Doxo-NE treated mice showed the highest ILS% as compared with the rest of the other treated groups. ATR-Doxo-NE and ATR-Doxo-Solution treated mice showed a significantly normalized level of hematological parameters. Moreover, the results from the kidney and liver enzymes showed the least toxic effects of Doxo-NE and ATR-Doxo-NE in comparison with Doxo-Sol and ATR-Doxo-Sol. Conclusion: Overall, the Doxo-NE and ATR-Doxo-NE formulations exhibited greater anti-cancer activity with less toxic effects.

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