Evaluating Niosomes Cytotoxicity on Fibroblast Cells: A Preliminary Step Towards Cancer Cell Assessment Using Telaglenastat as a Model Drug

The treatment of breast cancer frequently encounters difficulties as a result of the detrimental impact of traditional chemotherapy on normal cells. Niosomes, which are vesicles composed of non-ionic surfactants, present a promising approach for targeted drug delivery by encapsulating medicines that are both hydrophilic and hydrophobic. This work investigates the cytotoxic effects of Telaglenastat (TEL), a glutaminase inhibitor, when encapsulated in niosomes and administered to normal fibroblast and breast cancer cells. TEL-loaded niosomes were created by varying the molar ratios of Span 60 and cholesterol in order to evaluate their physical and chemical characteristics as well as their cytotoxicity. The encapsulation efficiency (EE%) of TEL in niosomes was determined to be 76.21 ± 2.53% for T1, 85.05 ± 0.24% for T2, and 58.95 ± 6.85% for T3 formulations. The particle sizes measured were 239.0 ± 2.9 nm for T1, 223.1 ± 3.0 nm for T2, and 255.1 ± 276.0 nm for T3. At pH 7.4, the release rates of TEL were 33.07 ± 6.64% for T1, 12.10 ± 0.82% for T2, and 25 ± 3.28% for T3. At pH 5.5, the release rates were 51.32 ± 3.40% for T1, 23.41 ± 2.44% for T2, and 33.67 ± 3.34% for T3 during a period of 48 h. Among these, T1, with the lowest concentration of Span 60 to cholesterol (25 mM:25 mM), showed the lowest cytotoxicity at the highest concentration, which is consistent with the non-toxic nature of its niosomal components. Furthermore, the study evaluated the anticancer activity of TEL as a free drug and NP formulation (T1) on BT-474 and MDA-MB-157 breast cancer cell lines, demonstrating that TEL NPs significantly enhanced cytotoxic effects compared to free TEL, suggesting superior efficacy of the nanoparticle formulation in reducing cell viability in these cancer models. Taken together, this underscores the potential of TEL-loaded niosomes as a treatment for breast cancer and highlights the importance of optimizing niosome composition to minimize adverse effects and enhance therapeutic efficacy.