Combining more than one anticancer agent in a nanocarrier is beneficial in producing a formula with a low dose and limited adverse side effects. The current study aimed to formulate docetaxel (DTX) and thymoquinone (TQ) in borage oil-based nanoemulsion (B-NE) and evaluate its potential in impeding the growth of breast cancer cells. The formulated B-NE and the combination (DTX + TQ) B-NE were prepared by the ultra-sonication method and physically characterized by the dynamic light scattering techniques. The cytotoxicity analyses of (DTX + TQ) B-NE in MCF-7 and MDA-MB-231 cells were evaluated in vitro by using the SRB assay. Cell death mechanisms were investigated in terms of apoptosis and autophagy pathways by flow cytometry. The optimum mean droplet sizes formulated for blank B-NE and the (DTX + TQ) B-NE were 56.04 ± 4.00 nm and 235.00 ± 10.00 nm, respectively. The determined values of the half-maximal inhibitory concentration (IC₅₀) of mixing one-half amounts of DTX and TQ in B-NE were 1.15 ± 0.097 µM and 0.47 ± 0.091 µM in MCF-7 and MDA-MB-231 cells, respectively, which were similar to the IC₅₀ values of the full amount of free DTX in both tested cell lines. The treatment with (DTX + TQ) B-NE resulted in a synergistic effect on both tested cells. (DTX + TQ) B-NE induced apoptosis that was integrated with the stimulation of autophagy. The produced formulation enhances the DTX efficacy against human breast cancer cells by reducing its effective dose, and thus it could have the potential to minimize the associated toxicity.

The chemotherapeutic drugs, loaded in nanocarriers, have recently attracted the pharmaceutical industries due to their limited adverse side effects. The objective of the current study was to incorporate the ifosfamide (IFO) into two different essential oils-based nanoemulsions, lemon (LEM-IFO) and salvia (SAL-IFO). The antiproliferation activities of the resulted formulas were evaluated in the MCF-7 breast cancer cells and HeLa cervical cancers cells. The cytotoxic effect of the NE formulas was detected by the MTT assay, DAPI stain and light microscopy. The z-average diameters range of LEM-IFO and SAL-IFO, determined by the zetasizer, were 49.15–61.81 nm and 56.64–64.62 nm, respectively. The half maximal inhibitory concentration (IC₅₀) of LEM-IFO and SAL-IFO, applied into the HeLa cells, were 0.165 ± 0.025 and 0.141 ± 0.035 mM, respectively, whereas the IC₅₀ of LEM-IFO and SAL-IFO subjected into the MCF-7 cells were 0.200 ± 0.005 mM and 0.270 ± 0.025 mM, respectively. The IC₅₀ of the free IFO was markedly larger than LEM-IFO and SAL-IFO when applied into MCF-7 cells (9.20 ± 2.01 mM) and HeLa cells (7.69 ± 1.88 mM). Among the tested formulas, LEM-IFO and SAL-IFO have the greatest apoptotic effect on the MCF-7 and HeLa cells, respectively. Solubilizing the IFO in the essential oils-based NE has ameliorated the antitumor efficacy of IFO.

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.