Louis Dina, Rizkalla Christianne Mounir Zaki, Rashad Amira
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo, Egypt.
Drug Des Devel Ther. 2024 Dec 19;18:6173-6184. doi: 10.2147/DDDT.S499068. eCollection 2024.
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.
NITRO Cubosomes were developed using hot homogenization according to 2-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.
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.
Nitrofurantoin cubosomes can be candidates for repositioning in breast cancer management after encouraging further stability and in-vivo studies.
呋喃妥因（NITRO）是一种长期用于治疗尿路感染的抗生素，可被硝基还原酶激活。这种激活机制促使人们探索其在控制和治疗表达硝基还原酶基因的乳腺癌方面的重新定位应用。
根据二因素析因设计，采用热均质法制备NITRO立方液晶纳米粒。研究的因素包括药物与油相的比例（1:10和2:10）、油相与水相的比例（1:10和1:5）以及单油酸甘油酯（GMO）与泊洛沙姆407（PX407）的比例（0.25:1和0.5:1）。共提出8个体系，并通过测量粒径、zeta电位、多分散指数和包封率进行评估。
S6（药物:油相比例为1:10，油相:水相比例为1:5，GMO:PX407比例为0.5:1）粒径为45.5±1.1nm，包封率为98.6±1.8%，表现出最高的综合可取性，被选作进一步分析。使用透射电子显微镜对S6的形态进行了检查。通过MTT试验研究了S6中NITRO的激活对MCF-7乳腺癌细胞系细胞内活力的影响。结果表明，与游离NITRO（174.54±1.36μg/mL）相比，S6的IC50值最低（83.99±0.15μg/mL），表明其疗效比游离NITRO有所提高。
在进一步进行稳定性和体内研究后，呋喃妥因立方液晶纳米粒有望成为乳腺癌治疗重新定位的候选药物。
