Mahkam Mehrdad, Bazmi Zeynabad Fatemeh, Alizadeh Effat, Rahimi Mahdi, Rahimi Fariborz, Salehi Roya
Chemistry Department, Azarbaijan Shahid Madani University, Tabriz, Iran.
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2021 May;11(3):477-489. doi: 10.34172/apb.2021.055. Epub 2020 Jul 1.
In last decades, by increasing multi-drug resistant microbial pathogens an urgent demand was felt in the development of novel antimicrobial agents. Promising nanocomposites composed of clay/alginate/imidazolium-based ionic liquid, have been developed via intercalation of calcium alginate and ionic liquid by ion exchange method. These tailored nanocomposites were used as nanocarriers to simultaneously deliver methotrexate (MTX), and ciprofloxacin (CIP), as anticancer and antibacterial agents, respectively to MCF-7 breast cancer cells. Nanocomposites were fully characterized by scanning electron microscopy studies (SEM), X-ray diffraction (XRD), Fourier transforms infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA) methods. The in vitro antimicrobial potential of the mentioned nanocomposites in free and dual-drug loaded form was investigated on Pseudomonas aeruginosa and Escherichia coli bacteria. The antitumor activity of nano-formulations was evaluated by both MTT assay and cell cycle arrest. The dual drug-loaded nanocomposites with exceptionally high loading efficiency (MTX: 99 ±0.4% and CIP: 98 ±1.2%) and mean particle size of 70 nm were obtained with obvious pH-responsive MTX and CIP release (both drugs release rate was increased at pH 5.8 compared to 7.4). The antibacterial activity of CIP-loaded nanocomposites was significantly higher in comparison with free CIP ( <0.001). The antitumor activity results revealed that MTX cytotoxicity on MCF-7 cells was significantly higher in nano-formulations compared to free MTX ( <0.001). Both MTX-loaded nanocomposites caused S-phase arrest in MCF-7 cells compared to non-treated cells ( ˂ 0.001). Newly developed smart nanocomposites are potentially effective pH-sustainable delivery systems for enhanced tumor therapy.
在过去几十年中，由于多重耐药微生物病原体不断增加，对新型抗菌剂的开发产生了迫切需求。通过离子交换法将海藻酸钙和离子液体插层，制备了由粘土/海藻酸盐/咪唑基离子液体组成的有前景的纳米复合材料。这些定制的纳米复合材料被用作纳米载体，分别将抗癌药物甲氨蝶呤（MTX）和抗菌药物环丙沙星（CIP）同时递送至MCF-7乳腺癌细胞。通过扫描电子显微镜研究（SEM）、X射线衍射（XRD）、傅里叶变换红外（FTIR）光谱和热重分析（TGA）方法对纳米复合材料进行了全面表征。研究了上述纳米复合材料在游离和载双药形式下对铜绿假单胞菌和大肠杆菌的体外抗菌潜力。通过MTT法和细胞周期阻滞评估了纳米制剂的抗肿瘤活性。获得了具有极高负载效率（MTX：99±0.4%和CIP：98±1.2%）且平均粒径为70 nm的载双药纳米复合材料，MTX和CIP具有明显的pH响应释放（与pH 7.4相比，两种药物在pH 5.8时的释放速率均增加）。载CIP纳米复合材料的抗菌活性明显高于游离CIP（<0.001）。抗肿瘤活性结果表明，与游离MTX相比，纳米制剂中MTX对MCF-7细胞的细胞毒性显著更高（<0.001）。与未处理的细胞相比，两种载MTX纳米复合材料均导致MCF-7细胞停滞在S期（<0.001）。新开发的智能纳米复合材料是潜在有效的pH可持续递送系统，可增强肿瘤治疗效果。
