Purpose: To evaluate the antitumor activity of gemcitabine (GEM), incorporated in microemulsions with varying surfactant-to-oil (S/O) ratio, against MCF-7 breast cancer cells and HCT . Conclusion: Microemulsion formulations improved the efficacy of GEM and induced apoptosis in

Summary Gemcitabine (GEM) is a chemotherapeutic agent with several dose limitation aspects. It was encapsulated in three microemulsion (ME) formulations with nanoparticles that differ in polarity: hydrophilic MEa, hydrophobic MEb and relatively neutral MEc. The apoptotic effect of the ME formulations was evaluated in the A549 non-small cell lung cancer cells, whereas the side effects of the formulas on the healthy cells were tested in the HFS human foreskin cells. The cell toxicity of all GEM-loaded-MEs (MEa+, MEb+ and MEc+) and free GEM solutions at concentrations of 1 and 10 µM was determined by using sulphorhodamine B (SRB) assay, while the mechanism of cell death was assessed by using ApopNexin FITC apoptosis detection kit and viewing the ultrastructure of treated A549 cells by using transmission electron microscope (TEM). It has been found that 10 µM of MEb+ (MEb10+) has the best antiproliferative and apoptotic effect compared to all of the ME formulations and GEM solutions. MEb10+ reduced the percentages of A549 cell viabilities to 11.15 1.4 whereas 10 µM of GEM (GEM10) decreased the percentages of A549 cell viabilities to 58.09 2.5. This study verified that ME formulations with hydrophobic droplets improved the therapeutic potential of GEM as an anticancer drug.