Basheer Haneen A, Alhusban Maram A, Zaid Alkilani Ahlam, Alshishani Anas, Elsalem Lina, Afarinkia Kamyar
Department of Pharmacy, Faculty of Pharmacy, Zarqa University, Zarqa 13110, Jordan.
Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
Cancers (Basel). 2023 Oct 16;15(20):5004. doi: 10.3390/cancers15205004.
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 ( < 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.
乳腺癌仍然是一个全球范围内备受关注的重大健康问题，需要持续研究创新的治疗方法。在此，我们报告了首次关于将游离形式和脂质体形式的二甲双胍（MET）与塞来昔布（CXB）联合用于治疗乳腺癌的疗效研究。我们的研究包括对这些脂质体药物载体的表征、稳定性评估及其对乳腺癌细胞模型的影响。采用薄膜水化技术制备了具有球形、均一尺寸分布和高包封率的脂质体。通过透射电子显微镜（TEM）、粒度分析仪和衰减全反射傅里叶变换红外光谱（ATR-FTIR）对脂质体进行了表征。MET和CXB脂质体的平均粒径分别为110.6±0.6和96.7±0.7，在4℃储存三个月时稳定，药物泄漏极少，包封率和粒径变化较小，理化参数未变。二维（2D）和三维（3D）活力测定评估表明，与游离药物相比，包封药物的细胞毒性增加。此外，与单独给药的每种药物相比，二甲双胍脂质体颗粒（MET NPs）和塞来昔布脂质体颗粒（CXB NPs）的组合在2D和3D模型中均导致细胞活力降低。在比较脂质体联合药物与游离药物联合对细胞迁移的影响时，我们发现两种干预措施均能有效阻止细胞迁移。然而，脂质体联合药物的疗效并不优于游离药物联合（P<0.05）。总之，本研究结果为MET和CXB纳米颗粒递送系统联合应用于乳腺癌治疗的潜在应用提供了有价值的见解。探索该药物递送系统的体内应用可能为乳腺癌患者开辟更有效、更具针对性的治疗方法的新途径。
