Multiple potential
drug delivery strategies have emerged as a result of recent advances in nanotechnology and nanomedicine. The aim of this research was to prepare an optimized system of PEGylated
gingerol-loaded
niosomes (Nio-Gin@PEG) as an excellent candidate for the treatment of human
breast cancer cells. The preparation procedure was modified by adjusting the
drug concentration,
lipid content, and Span60/Tween60 ratio, resulting in high encapsulation efficacy (EE%), rapid release rate, and reduced size. The Nio-Gin@PEG exhibited significantly improved storage stability compared to the
gingerol-loaded
niosomes formulation (Nio-Gin), with minimal changes in EE%, release profile, and size during storage. Furthermore, Nio-Gin@PEG demonstrated pH-dependent release behavior, with delayed
drug diffusion at physiological pH and significant
drug diffusion under acidic conditions (pH = 5.4), making it a promising option for
cancer treatment. Cytotoxicity tests indicated that Nio-Gin@PEG possessed excellent biocompatibility with human fibroblast cells while exerting a remarkable inhibitory effect on MCF-7 and SKBR3
breast cancer cells, attributed to the presence of
gingerol and the PEGylated structure in the preparation. Nio-Gin@PEG also exhibited the ability to modulate the expression of target genes. We observed statistically significant down-regulation of the expression of BCL2, MMP2, MMP9, HER2, CCND1, CCNE1, BCL2, CDK4, and
VEGF genes, along with up-regulation of the expression of BAX, CASP9,
CASP3, and P21 genes. Flow cytometry results revealed that Nio-Gin@PEG could induce a higher rate of apoptosis in both cancerous cells compared to
gingerol and Nio-Gin, owing to the optimal encapsulation and efficient drug release from the formulation, as confirmed by cell cycle tests. ROS generation demonstrated the superior
antioxidant effect of Nio-Gin@PEG compared to other prepared formulations. The results of this study emphasize the potential of formulating highly biocompatible
niosomes in the future of nanomedicine, enabling more precise and effective treatment of
cancers.