Cubosomes as Delivery System to Repositioning Nitrofurantoin in Breast Cancer Management

Dina Louis,1,2,* Christianne Mounir Zaki Rizkalla,1 Amira Rashad3,* 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo, Egypt; 3Department of Pharmaceutical Technology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt*These authors contributed equally to this workCorrespondence: Dina Louis, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr Eleini Street, Cairo, 11562, Egypt, Tel +202 01228866769, Email [email protected]: 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 23-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.Keywords: nitro reductase, glyceryl monooleate, Poloxamer 407, MTT assay, factorial design