Asghari Lalami Zahra, Tafvizi Farzaneh, Naseh Vahid, Salehipour Masoud
Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec;396(12):3867-3886. doi: 10.1007/s00210-023-02579-2. Epub 2023 Jun 27.
Multiple potential drug delivery strategies have emerged as a result of recent advances in nanotechnology and nanomedicine. The aim of this research was to prepare an optimized system of PEGylated gingerol-loaded niosomes (Nio-Gin@PEG) as an excellent candidate for the treatment of human breast cancer cells. The preparation procedure was modified by adjusting the drug concentration, lipid content, and Span60/Tween60 ratio, resulting in high encapsulation efficacy (EE%), rapid release rate, and reduced size. The Nio-Gin@PEG exhibited significantly improved storage stability compared to the gingerol-loaded niosomes formulation (Nio-Gin), with minimal changes in EE%, release profile, and size during storage. Furthermore, Nio-Gin@PEG demonstrated pH-dependent release behavior, with delayed drug diffusion at physiological pH and significant drug diffusion under acidic conditions (pH = 5.4), making it a promising option for cancer treatment. Cytotoxicity tests indicated that Nio-Gin@PEG possessed excellent biocompatibility with human fibroblast cells while exerting a remarkable inhibitory effect on MCF-7 and SKBR3 breast cancer cells, attributed to the presence of gingerol and the PEGylated structure in the preparation. Nio-Gin@PEG also exhibited the ability to modulate the expression of target genes. We observed statistically significant down-regulation of the expression of BCL2, MMP2, MMP9, HER2, CCND1, CCNE1, BCL2, CDK4, and VEGF genes, along with up-regulation of the expression of BAX, CASP9, CASP3, and P21 genes. Flow cytometry results revealed that Nio-Gin@PEG could induce a higher rate of apoptosis in both cancerous cells compared to gingerol and Nio-Gin, owing to the optimal encapsulation and efficient drug release from the formulation, as confirmed by cell cycle tests. ROS generation demonstrated the superior antioxidant effect of Nio-Gin@PEG compared to other prepared formulations. The results of this study emphasize the potential of formulating highly biocompatible niosomes in the future of nanomedicine, enabling more precise and effective treatment of cancers.
由于纳米技术和纳米医学的最新进展，多种潜在的药物递送策略应运而生。本研究的目的是制备一种优化的聚乙二醇化姜辣素负载脂质体系统（Nio-Gin@PEG），作为治疗人类乳腺癌细胞的优秀候选物。通过调整药物浓度、脂质含量和司盘60/吐温60比例对制备工艺进行了改进，从而获得了高包封率（EE%）、快速释放率和减小的粒径。与姜辣素负载脂质体制剂（Nio-Gin）相比，Nio-Gin@PEG表现出显著提高的储存稳定性，在储存期间EE%、释放曲线和粒径的变化最小。此外，Nio-Gin@PEG表现出pH依赖性释放行为，在生理pH下药物扩散延迟，在酸性条件（pH = 5.4）下药物显著扩散，这使其成为癌症治疗的一个有前景的选择。细胞毒性试验表明，Nio-Gin@PEG与人成纤维细胞具有良好的生物相容性，同时对MCF-7和SKBR3乳腺癌细胞具有显著的抑制作用，这归因于制剂中姜辣素的存在和聚乙二醇化结构。Nio-Gin@PEG还表现出调节靶基因表达的能力。我们观察到BCL2、MMP2、MMP9、HER2、CCND1、CCNE1、BCL2、CDK4和VEGF基因的表达在统计学上显著下调，同时BAX、CASP9、CASP3和P21基因的表达上调。流式细胞术结果显示，与姜辣素和Nio-Gin相比，Nio-Gin@PEG可诱导两种癌细胞更高的凋亡率，细胞周期试验证实这归因于制剂的最佳包封和高效药物释放。活性氧生成表明Nio-Gin@PEG与其他制备的制剂相比具有优异的抗氧化作用。本研究结果强调了在纳米医学未来中制备高度生物相容性脂质体的潜力，能够更精确有效地治疗癌症。
