Abstract
PURPOSE: Nitrofurantoin (NITRO), a long-standing antibiotic to treat urinary tract infections, is activated by Nitro reductases. This activation mechanism has led to its exploration for repositioning applications in controlling and treating breast cancer, which express a Nitro reductase gene. METHODS: NITRO Cubosomes were developed using hot homogenization according to 2(3)-full factorial design. The factors studied included the ratio of drug to oily phase (1:10 and 2:10), the ratio of oily to aqueous phase (1:10 and 1:5), and the ratio of Glyceryl mono-oleate (GMO) to Poloxamer 407 (PX407) (0.25:1 and 0.5:1). A total of 8 systems were proposed and evaluated by measuring particle size, zeta potential, polydispersity index, and percentage of entrapment efficiency. RESULTS: S6 (1:10 drug: oily phase, 1:5 oily: aqueous phase and 0.5:1 GMO: PX407) with particle size 45.5 ±c1.1 nm and an entrapment efficiency of 98.6 ± 1.8% exhibited highest desirability and was selected for further analysis. The morphology of S6 was examined using TEM microscopy. The activation of NITRO from S6 reflected on intracellular viability of MCF-7 breast cancer cell line was investigated by an MTT assay. The findings indicated that S6 had the lowest IC50 value (83.99 ± 0.15 μg g/mL) compared to Free NITRO (174.54 ± 1.36 μg g/mL), suggesting enhanced efficacy compared to free NITRO. CONCLUSION: Nitrofurantoin cubosomes can be candidates for repositioning in breast cancer management after encouraging further stability and in-vivo studies.