Abstract

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.

摘要

甲氨蝶呤（MTX）是一种化学治疗剂，由于其对肺和神经有毒性，因此在临床上的应用受到限制。在A549非小细胞肺癌细胞中评估了在椰子油纳米乳剂（NE）中配制的MTX的MTX-NE COCO的抗肿瘤活性，同时在小鼠中评估了其对肺和脑氧化应激的不良副作用。MTX-NE COCO的分散纳米液滴的z平均直径（79.74±3.49 nm）大大大于游离NE COCO（64.80±3.34 nm）。相反，MTX-NE COCO的负z电位值（3.00±0.69 mV）明显小于自由NE COCO的负z电位（8.20±0.76 mV）。最小抑菌浓度（IC ₅₀MTX-NE的COCO（18±1.8 µM）比游离MTX（32±1.2 µM）的IC _50小两倍左右。在体内的MTX-NE COCO治疗的评估表明，脑和肺组织的抗氧化酶活性，过氧化氢酶，超氧化物歧化酶和谷胱甘肽还原酶，进行相对比较自由MTX治疗时升高而丙二醛量减少。总之，在NE中将MTX与椰子油混合使用可改善其功效，同时改善其对脑和肺的氧化应激作用。