Incorporation of methotrexate into coconut oil nanoemulsion potentiates its antiproliferation activity and attenuates its oxidative stress

Drug Deliv. 2020 Dec;27(1):422-430. doi: 10.1080/10717544.2020.1736209.


Methotrexate (MTX), a chemotherapeutic agent, has limited clinical applications due to its pulmonary and neurotoxicity. The antineoplastic activity of MTX-NE COCO, which is MTX formulated in coconut oil nanoemulsion (NE), was evaluated in A549 non-small cell lung cancer cells while its adverse side effects on the oxidative stress of the lung and brain were assessed in mice. The z-average diameter for the dispersed nanodroplet of MTX-NE COCO (79.74 ± 3.49 nm) was considerably greater than the free-NE COCO (64.80 ± 3.34 nm). In contrast, the magnitude of the negative z-potential of MTX-NE COCO (3.00 ± 0.69 mV) was markedly less than that of free-NE COCO (8.20 ± 0.76 mV). The minimum inhibitory concentration (IC50) of MTX-NE COCO (18 ± 1.8 µM) was less than the IC50 of free MTX (32 ± 1.2 µM) by around twofold. The in vivo evaluation of the MTX-NE COCO treatment revealed that the antioxidant enzymes activities of the brain and lung tissues, catalase, superoxide dismutase, and glutathione reductase, were relatively raised while the malondialdehyde amount was diminished when compared to the free MTX treatment. In conclusion, combining MTX with coconut oil in a NE had improved its efficacy while ameliorating its oxidative stress effect on the brain and lungs.

Keywords: A549 non-small cell lung cancer cells; Chemotherapeutic agents; Ehrlich ascites carcinoma; essential oils; nanocarrier.

Publication types

  • Comparative Study

MeSH terms

  • A549 Cells
  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / toxicity
  • Carcinoma, Ehrlich Tumor / drug therapy
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Coconut Oil / chemistry
  • Emulsions
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy*
  • Methotrexate / administration & dosage*
  • Methotrexate / pharmacology
  • Methotrexate / toxicity
  • Mice
  • Nanoparticles*
  • Oxidative Stress / drug effects
  • Particle Size


  • Antimetabolites, Antineoplastic
  • Emulsions
  • Coconut Oil
  • Methotrexate

Grants and funding

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant No. DF-692-165-1441. The authors, therefore, acknowledge DSR technical and financial support.