Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells.

Ellagic acid has recently attracted increasing attention regarding its role in the prevention and treatment of cancer. Surface functionalized nanocarriers have been recently studied for enhancing cancer cells' penetration and achieving better tumor-targeted delivery of active ingredients. Therefore, the present work aimed at investigating the potential of APA-functionalized emulsomes (EGA-EML-APA) for enhancing cytototoxic activity of EGA against human breast cancer cells. Phospholipon 90 G: cholesterol molar ratio (PC: CH; X, mole/mole), Phospholipon 90 G: Tristearin weight ratio (PC: TS; X, /) and apamin molar concentration (APA conc.; X, mM) were considered as independent variables, while vesicle size (VS, Y, nm) and zeta potential (ZP, Y, mV) were studied as responses. The optimized formulation with minimized vs. and maximized absolute ZP was predicted successfully utilizing a numerical technique. EGA-EML-APA exhibited a significant cytotoxic effect with an IC value of 5.472 ± 0.21 µg/mL compared to the obtained value from the free drug 9.09 ± 0.34 µg/mL. Cell cycle profile showed that the optimized formulation arrested MCF-7 cells at G2/M and S phases. In addition, it showed a significant apoptotic activity against MCF-7 cells by upregulating the expression of and and downregulating . Furthermore, NF-κB activity was abolished while the expression of was increased confirming the significant apoptotic effect of EGA-EML-APA. In conclusion, apamin-functionalized emulsomes have been successfully proposed as a potential anti-breast cancer formulation.