Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
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 -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 -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 (IC) of MTX-NE COCO (18 ± 1.8 µM) was less than the IC of free MTX (32 ± 1.2 µM) by around twofold. The 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.
甲氨蝶呤（MTX）是一种化疗药物，但由于其具有肺毒性和神经毒性，其临床应用受到限制。本研究评估了甲氨蝶呤-椰子油纳米乳（MTX-NE COCO）在 A549 非小细胞肺癌细胞中的抗肿瘤活性，同时评估了其在小鼠肺部和脑部氧化应激方面的不良反应。MTX-NE COCO 的分散纳米液滴的平均直径（79.74 ± 3.49nm）明显大于游离 NE COCO（64.80 ± 3.34nm）。相比之下，MTX-NE COCO 的负电位（3.00 ± 0.69mV）明显小于游离 NE COCO（8.20 ± 0.76mV）。MTX-NE COCO 的最低抑制浓度（IC）（18 ± 1.8µM）约为游离 MTX（32 ± 1.2µM）的两倍。与游离 MTX 相比，MTX-NE COCO 治疗可使大脑和肺部组织的抗氧化酶（过氧化氢酶、超氧化物歧化酶和谷胱甘肽还原酶）的活性相对升高，丙二醛的含量降低。总之，将 MTX 与椰子油结合成 NE 可提高其疗效，同时减轻其对大脑和肺部的氧化应激作用。
