Nitroreductase-Activated Nitrofurantoin Encapsulated in Cubosomes for Enhanced Breast Cancer Treatment

Nitrofurantoin (NITRO), a time-honored antibiotic prescribed for urinary tract infections, relies on nitroreductases for its activation. This mode of action has spurred its evaluation for drug repurposing aimed at controlling and managing breast cancer, a malignancy that expresses a nitroreductase gene. NITRO-loaded cubosomes were prepared by hot homogenization using a 23 full-factorial design. The variables examined consisted of the drug-to-oily phase proportion (1:10 and 2:10), the oily-to-aqueous phase proportion (1:10 and 1:5), and the Glyceryl mono-oleate (GMO)-to-Poloxamer 407 (PX407) proportion (0.25:1 and 0.5:1). Eight distinct formulations were planned and appraised based on particle size, zeta potential, polydispersity index, and entrapment efficiency percentage. Formulation S6 (configured with 1:10 drug: oily phase, 1:5 oily: aqueous phase, and 0.5:1 GMO: PX407), exhibiting a particle size of 45.5 ± 1.1 nm alongside an entrapment efficiency of 98.6% ± 1.8%, achieved the highest desirability score and was singled out for deeper evaluation. TEM examined its morphology. The activation of NITRO delivered from S6, as measured by intracellular viability of MCF-7 breast cancer cells, was assessed using an MTT assay. Data demonstrated that S6 yielded the lowest IC50 (83.99 ± 0.15 μg g/mL), compared with Free NITRO (174.54 ± 1.36 μg g/mL), indicating superior potency relative to the free drug. Nitrofurantoin cubosomes are viable prospects for repurposing in breast cancer therapy, contingent on additional stability assessments and in vivo studies.