Enhanced Cytotoxicity of Eugenia aquea Extract-Loaded PLGA-PVA Nanoparticles Against MCF-7 Breast Cancer Cells

This study evaluates the anticancer potential of poly (lactic-co-glycolic acid)/polyvinyl alcohol (PLGA-PVA) nanoparticles (NPs) loaded with Eugenia aquea Burm. Fil (EA) leaf extract for breast cancer treatment. The ethanol extract of the leaves was obtained, followed by estimation of phenolic and flavonoid contents, and identification of phenolic acids and flavonoids via high-performance liquid chromatography (HPLC). Gallic acid, followed by cinnamic acid, are the major phenolic acids. Moreover, naringin and catechin are the major flavonoids. The single emulsion solvent evaporation method was employed for PLGA-PVA NPs synthesis, achieving a mean particle size of 249.3 ± 3.1 nm, a polydispersity index of 0.110 ± 0.02, and a zeta potential of-4.31 ± 0.08 mV. Antioxidant activity was confirmed through different assays: DPPH (IC₅₀: 16.25 µg.mL^⁻¹), ABTS (IC₅₀: 6.96 µg.mL^⁻¹), and FRAP (1449 µM Trolox equivalent/mg extract), indicating strong free radical scavenging abilities. In-vitro cytotoxicity tests on MCF-7 breast cancer cells revealed enhanced cytotoxicity for the EA-loaded PLGA-PVA NPs (IC₅₀: 120.2 ± 0.3 µg. mL^⁻¹) compared to non-encapsulated extract (IC₅₀: 163.04 ± 4.53 µg.mL^⁻¹) and plain PLGA-PVA NPs (IC₅₀: 267 ± 6.47 µg.mL^⁻¹). The DEVD cleavage assay shows that EA-PLGA-PVA-AA NPs induce the highest caspase-3 activity (1.33 absorbance, 4.53 ng•mg^⁻¹), suggesting enhanced apoptosis compared to other treatments. Additionally, gene expression analysis revealed a significant upregulation of the tumor suppressor gene P53 and a downregulation of the oncogene C-myc in cells treated with EA-PLGA-PVA-AA NPs. These findings demonstrate the potential of PLGA-PVA NPs as an effective delivery system for antioxidant-rich EA extract in breast cancer therapy and oxidative stress management.