Raloxifene-Loaded Lipid Nanovesicles: A Journey to Select the Optimal Nanocarrier Formulation Through Characterization and Cytotoxic Analysis.

: Cancer ranks as the second most prevalent cause of death worldwide, according to the World Health Organization. Approximately one in six global deaths is attributed to cancer. Among females, breast cancer stands out as the most frequent type of tumor. Raloxifene (RLX), recognized as a selective estrogen receptor modulator, has been employed as a therapeutic option in treating breast cancer among postmenopausal women. The objective of this study was to investigate the anticancer potential of raloxifene-loaded hexosomes, nanoliposomes, and nanoniosomes to identify the most effective formulation. : The particle size, zeta potential, entrapment efficiency, and structural elucidation of the various nanovesicle formulations was validated; : Each nanocarrier exhibited a negative surface charge, nanometric size, and a reasonable encapsulation efficiency. Cytotoxicity of the different raloxifene-loaded nanovesicles on MCF-7 breast cancer cell lines and MCF10 non tumorigenic cells revealed the substantial cytotoxic activity of the hexosomal nanocarrier compared to the other nanovesicles, exhibiting the lowest IC50 = 45.3 ± 1.10 µM. : The RLX-loaded hexosomal formulation showed superior cytotoxic activity, indicating its potential as a highly effective therapeutic agent. To fully understand its capabilities and mechanisms, further in vitro characterization studies are necessary.