Oxidative stress has been shown to be involved in cell death based on the extent of redox unbalance. It is known that cancer cells with increased oxidative stress are likely to be more vulnerable to damage by further ROS (reactive oxygen species) when compared to normal cells. The aim of this study was to evaluate the profile of ROS production by breast cancer cells (MCF-7 cells) in the presence of co-encapsulated anticancer drugs. We developed a novel liposomal formulation encapsulating paclitaxel (PCT) and docetaxel (DCT) and analysed the relation between ROS production and necrosis in MCF-7 cells. Liposomes were prepared by the thin film hydration method followed by extrusion through 100 nm polycarbonate membranes. Following extrusion, the non-encapsulated drug was removed by syringe filtration of the formulation through 0.22µm membranes. Liposomal drug concentrations were determined using reverse phase high performance liquid chromatography (HPLC). MCF-7 cells were incubated at 37°C, 5% CO<sub>2</sub> atmosphere in the presence of the formulations for 48 h. Necrosis and ROS generation were determined by flow cytometry (FACSCalibur, BD®, Biosciences, USA) using Propidium Iodide (BD®, Biosciences) and the oxidation of 2,7-dichlorodihydrofluorescein diacetate (Sigma Aldrich, USA), respectively. All results were performed in triplicate of three independent experiments. Data were submitted to ANOVA and the post-hoc Tukey statistical test, considering p&lt;0.05 as significant. The liposomal formulations exhibited a homogeneous size distribution of approximately 150 nm, with mean zeta potential of ca. -3 mV. A significant necrosis response and increased ROS production of PCT and DCT after encapsulation into liposomes were induced when compared to the free drugs. These findings suggest that oxidative stress can be involved in the progression of cell death caused by combination of PCT and DCT co-encapsulated drugs in liposomes.

Liposome-based co-delivery of paclitaxel and docetaxel enhances oxidative stress in MCF-7 breast cancer cells

253rd National Meeting (2017)

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