Breast cancer continues to be a prominent worldwide health concern and requires continued investigation into innovative therapeutic approaches. Here, we report the first investigation into the therapeutic efficacy of combining Metformin (MET) and Celecoxib (CXB), both in free and niosomal form, for the treatment of breast cancer. Our investigation encompassed the characterization of these niosomal drug carriers, their stability assessment, and their effect on breast cancer cell models. The thin-film hydration technique was employed to prepare niosomes with spherical, uniform-size distributions and high encapsulation efficiencies. The niosomes were characterized by TEM, particle size analyzer, and ATR-FTIR. The niosomes with an average size of 110.6 ± 0.6 and 96.7 ± 0.7, respectively, for MET and CXB were stable when stored at 4 °C for three months with minimal drug leakage, minor changes in encapsulation efficiency and size, and unchanged physicochemical parameters. Evaluation in two-dimensional (2D) and three-dimensional (3D) viability assays demonstrated an increased cytotoxicity of encapsulated drugs when compared to their free-drug counterparts. Additionally, the combination of Metformin Niosomal Particles (MET NPs) and Celecoxib Niosomal Particles (CXB NPs) led to decreased cell viability in both 2D and 3D models compared to each drug administered individually. When comparing the effect of the niosomal versus the free combination of the drugs on cell migration, we found that both interventions effectively prevented cell migration. However, the efficacy of the niosomes’ combination was not superior to that of the free drug combination (p< 0.05). In conclusion, the results of this study provide valuable insights into the potential application of combining MET and CXB nanoparticle delivery systems to breast cancer treatment. Exploring the in vivo application of this drug delivery system could open new avenues for more effective and targeted therapeutic approaches for breast cancer patients.
乳腺癌仍是全球范围内一个突出的健康问题，亟需持续探索创新的治疗方法。本研究首次探讨了二甲双胍（MET）与塞来昔布（CXB）以游离形式及囊泡载药形式联合治疗乳腺癌的疗效。研究涵盖了对囊泡载药体系的表征、稳定性评估及其对乳腺癌细胞模型的作用。采用薄膜水化法制备的囊泡呈球形、粒径分布均匀且具有高包封率。通过透射电镜、粒度分析仪及衰减全反射傅里叶变换红外光谱对囊泡进行表征，结果显示MET与CXB囊泡平均粒径分别为110.6±0.6 nm和96.7±0.7 nm，在4℃储存三个月期间保持稳定，药物泄漏极少，包封率与粒径变化微小，理化参数保持稳定。二维（2D）与三维（3D）细胞活力实验表明，与游离药物相比，囊泡封装药物的细胞毒性显著增强。此外，在2D和3D模型中，二甲双胍囊泡颗粒（MET NPs）与塞来昔布囊泡颗粒（CXB NPs）联合给药比单一用药更能降低细胞活力。在比较囊泡联合给药与游离药物联合给药对细胞迁移的影响时，发现两种干预方式均能有效抑制细胞迁移，但囊泡联合给药的疗效并未优于游离药物联合给药（p<0.05）。综上所述，本研究为MET与CXB纳米颗粒递送系统联合应用于乳腺癌治疗提供了重要参考。未来探索该给药体系的体内应用，或将为乳腺癌患者开发更有效、更具靶向性的治疗方案开辟新途径。
Niosomal Delivery of Celecoxib and Metformin for Targeted Breast Cancer Treatment
肿瘤(癌症)患者之家