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

Abstract

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; X1, mole/mole), Phospholipon® 90 G: Tristearin weight ratio (PC: TS; X2, w/w) and apamin molar concentration (APA conc.; X3, mM) were considered as independent variables, while vesicle size (VS, Y1, nm) and zeta potential (ZP, Y2, 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 IC50 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 p53, bax and casp3 and downregulating bcl2. Furthermore, NF-κB activity was abolished while the expression of TNfα 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.

Nanomedicine-Based Drug-Targeting in Breast Cancer: Pharmacokinetics, Clinical Progress, and Challenges

“…Doxil, the first US Food and Drug Administration (FDA)-approved chemotherapeutic nanosystem to be used therapeutically, contains doxorubicin (DOX). The PEGylated DOX liposomal formulation extends circulation time and prevents premature removal of the nanoformulation . For dual targeting, i.e.…”

“…Flow cytometric tests verified the improved cell penetration of the NLCs against the BT-474 cell line . Ellagic acid (EGA) is commonly used to prevent and treat cancer . A plethora of researchers have reported that surface-functionalized nanocarriers have been evaluated in tumor-targeted delivery of anticancer drugs .…”

“…Furthermore, tumor necrosis factor-α (TNF-α) expression was elevated. In contrast, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity was reduced, which supported the considerable induction of apoptosis by functionalized EGF-NLCs . Therefore, functionalized EGA-NLCs have been successfully proposed as effective lipidic nanocarriers in managing BC.…”

“…The PEGylated DOX liposomal formulation extends circulation time and prevents premature removal of the nanoformulation. 33 For dual targeting, i.e. , bone cancer and BC, Zhao and associates developed paclitaxel (PTX)-loaded liposomes.…”

“… 64 Ellagic acid (EGA) is commonly used to prevent and treat cancer. 33 A plethora of researchers have reported that surface-functionalized nanocarriers have been evaluated in tumor-targeted delivery of anticancer drugs. 33 The researcher who developed the apigenin-functionalized EGA-loaded NLCs demonstrated a substantial cytotoxic impact, with an IC 50 value of 5.472 μg/mL above that of the free drug reported at 9.09 μg/mL.…”