Al-Sawahli Majid M, A El-Feky Yasmin, Mohammed Ahmed J, M Mohamed Nada, El-Telbany Rania, Zuhair Alamri Zaenah, Jameel Melebary Sahar, Alfaifi Mohammad Y, I Elbehairi Serag Eldin, M Noreddin Ayman, B Abdel-Naim Ashraf, M Alolayan Ebtesam, El-Telbany Dalia F
Department of Pharmaceutics, College of Pharmacy, The Islamic University, Najaf, Iraq.
Department of Pharmaceutics, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo, Egypt.
Nanomedicine (Lond). 2025 Apr;20(8):817-833. doi: 10.1080/17435889.2025.2481823. Epub 2025 Apr 2.
The purpose of this study was to investigate comparatively the anticancer potential of Terbinafine loaded Dextran Sulphate coated Zein nanospheres against human prostate cancer PC3 cells to enhance the repurposing profile of terbinafine utilizing optimized nano-sized delivery systems.
MATERIALS & METHODS: The formula was fabricated using the thin film hydration technique. Particle size analysis, drug diffusion, and encapsulation efficiency were considered when evaluating the fabricated formula, which were developed using a Box-Behnken statistical design.
Due to the formula optimization, the mean particle size was 273.2 ± 1.98 nm, the zeta potential was -38.4 ± 2.77 mV, and the amount released after 36 h was 97.4 ± 5.7%. The formula exhibited significantly reduced IC in PC3 cells by around 14-fold. A higher cellular uptake was observed. The cell cycle assay results obtained suppression of the proliferation, especially in the G/G and S phases. This pro-apoptotic pattern of the optimized formula was confirmed by the increased mRNA expression of CASP3 and P53 and reduced expression of CDK1, CDK7, and CDK9. Furthermore, a higher production of reactive oxygen species was achieved.
The optimized formula revealed enhanced pro-apoptosis in PC3 cells which support the repurposing profile of terbinafine toward prostate cancer.
本研究旨在比较载有特比萘芬的硫酸葡聚糖包被玉米醇溶蛋白纳米球对人前列腺癌PC3细胞的抗癌潜力,以利用优化的纳米级递送系统提高特比萘芬的重新利用价值。
采用薄膜水化技术制备该配方。在评估所制备的配方时,考虑了粒径分析、药物扩散和包封率,这些配方是使用Box-Behnken统计设计开发的。
由于配方优化,平均粒径为273.2±1.98nm,zeta电位为-38.4±2.77mV,36小时后释放量为97.4±5.7%。该配方在PC3细胞中的IC显著降低约14倍。观察到更高的细胞摄取。细胞周期分析结果显示增殖受到抑制,尤其是在G/G和S期。优化配方的这种促凋亡模式通过CASP3和P53的mRNA表达增加以及CDK1、CDK7和CDK9的表达降低得到证实。此外,还实现了更高的活性氧生成。
优化后的配方显示出PC3细胞中促凋亡作用增强,这支持了特比萘芬对前列腺癌的重新利用价值。