Mayson H. Alkhaitb* and Dalal A. Al-Saedi Pages 625 - 633 ( 9 )
Background: The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize drug efficacies. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations.
Objective: The study aimed to evaluate antitumor activity of the combination therapy of GEM and ATV encapsulated in nanodroplets of microemulsion (ME) formulation in MCF-7 breast cancer cells and healthy HFS human foreskin cells.
Method: The physical characterization of drug formulas has been studied by the transmission electron microscope (TEM). The cytotoxicity and efficacy of the formulation were examined by 3(4,5-dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay, light microscopy, and ApopNexin apoptosis detection kit.
Results: It has been found that the IC50, inhibitory concentration at which 50 percent of the cells inhibited, for the combination of GEM and ATV at 1:2 ratio, respectively, in the ME (GEM/2ATVME) with a droplet diameter of 4.81±0.86 nm, subjected into the MCF-7 cells for 24h, was similar to the combination of GEM and ATV at 1:1 ratio, respectively, in water (GEM/ATV). According to the FITC/PI assay, 5 µM of GEM/2ATV-ME was less toxic on the HFS cells as higher percentages of viable cells (85.15%) were detected when compared to the GEM/ATV that caused reduction in the percentages of the viable cells (66.45%).
Conclusion: Formulating GEM with ATV in ME has improved the therapeutic anticancer potential of both drugs while reducing their side effects on the normal cells.
Drug delivery, antitumor activity, MTT assay, appopNexin apoptosis detection kit, microemulsion, transmission electron microscope.
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah