• Ahmet Doğan Ergin, Çağatay Oltulu, Nebiye Pelin Türker, and Gülen Melike Demirbolat.
• Department of Neuroscience, University of Torino, Torino, Italy; Department of Pharmaceutical Technology, Faculty of Pharmacy, Trakya University, Edirne, Turkiye.
• Turk J Med Sci. 2023 Aug 1; 53 (4): 872882872-882.

BackgroundMethotrexate (MTX) is a folic acid antagonist that is widely used to treat osteosarcoma, leukemia, breast cancer, and autoimmune and inflammatory diseases. The most important concerns with MTX are its poor solubility and high toxicity, particularly in liver cells. To enhance its solubility and to minimize its toxicity, we encapsulated MTX in niosomes and investigated its hepatotoxicity mechanisms using genetic biomarkers.MethodsNiosomes were successfully prepared using a modified thin film method, and the prepared monodisperse smallsized formulation was subsequently characterized. In vitro cytotoxicity studies were performed both in hepatocarcinoma (HEP3G) and healthy liver (AML12) cell lines. Specifically, immunofluorescence assay and evaluation of the expression levels of apoptotic, antioxidant, heat shock protein, and oxidative stress genes were performed.ResultsThe formulation had a particle size of 117.1 ± 33 nm, a surface charge of -38.41 ± 0.7 mV, and an encapsulation efficiency of 59.7% ± 2.3%. The results showed that the niosomal formulation exhibited significantly higher cytotoxic effects in HEP3G than in AML12. The immunofluorescence and genetic analyses showed that the increased cytotoxicity of niosomes resulted mainly from oxidative stress and slight apoptosis.DiscussionThese results demonstrated that niosomal drug delivery systems could be a new potential formulation for minimizing MTX-related hepatotoxicity.

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