Nitte (Deemed to be University), Department of Bio and Nano Technology, Nitte University Centre for Science Education and Research, Deralakatte, Mangalore, 575018, India.
Nitte (Deemed to be University), Department of Bio and Nano Technology, Nitte University Centre for Science Education and Research, Deralakatte, Mangalore, 575018, India.
Microb Pathog. 2024 Dec;197:107087. doi: 10.1016/j.micpath.2024.107087. Epub 2024 Oct 29.
Increasing antibiotic resistance in bacterial infections, including drug-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), necessitates innovative therapeutic solutions. Silver nanoparticles are promising for combating infections, but toxicity concerns emphasize the importance of factors like dosage, size, shape, and surface chemistry. Hence, exploring poloxamer as a stabilizing agent to reduce its toxicity and enhance the antibacterial effect on MRSA is investigated.
Silver nanoparticles stabilized with poloxamer (AgNPs@Pol) were synthesized through the chemical reduction method and characterized using UV-visible spectrophotometer, HR-TEM, DLS, and Zeta potential measurements. Subsequently, the antibacterial activity of AgNPs@Pol alone and in combination with methicillin against MRSA and methicillin-susceptible S. aureus (MSSA) was evaluated using the broth microdilution method.
AgNPs@Pol showed significant efficacy against MRSA and MSSA, achieving a 100 % reduction in colony-forming units (CFU) at 9.7 μg/ml. The minimum inhibitory concentration (MIC) against MRSA and MSSA was 8.6 μg/ml and 4.3 μg/ml, respectively. A synergistic effect was observed when AgNPs@Pol was combined with methicillin. Treatment with AgNPs@Pol increased reactive oxygen species (ROS) production in both strains, contributing to its antibacterial activity. Real-time qPCR analysis indicated the downregulation of genes involved in antimicrobial resistance and cell adhesion in both strains. Further, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated low cytotoxicity for AgNPs@Pol against MCF-7, MG-63, and NIH-3T3 cell lines.
The developed AgNPs@Pol demonstrated extensive colloidal stability, potent antibacterial activity and synergistic effect with methicillin against MRSA and MSSA. Further studies in primary cells and in vivo models may validate its potential for clinical applications.
细菌感染中的抗生素耐药性不断增加，包括耐甲氧西林金黄色葡萄球菌（MRSA）等耐药菌株，这就需要创新的治疗方法。纳米银颗粒在抗感染方面具有广阔的应用前景，但毒性问题凸显了剂量、尺寸、形状和表面化学等因素的重要性。因此，探索泊洛沙姆作为稳定剂，以降低其毒性并增强其对 MRSA 的抗菌效果。
通过化学还原法合成了泊洛沙姆稳定的纳米银颗粒（AgNPs@Pol），并使用紫外可见分光光度计、高分辨率透射电子显微镜（HR-TEM）、动态光散射（DLS）和 Zeta 电位测量对其进行了表征。随后，采用肉汤微量稀释法评估了 AgNPs@Pol 单独使用以及与甲氧西林联合使用对 MRSA 和甲氧西林敏感金黄色葡萄球菌（MSSA）的抗菌活性。
AgNPs@Pol 对 MRSA 和 MSSA 表现出显著的疗效，在 9.7μg/ml 时可使菌落形成单位（CFU）完全减少。对 MRSA 和 MSSA 的最小抑菌浓度（MIC）分别为 8.6μg/ml 和 4.3μg/ml。AgNPs@Pol 与甲氧西林联合使用时观察到协同作用。AgNPs@Pol 处理可增加两种菌株中活性氧（ROS）的产生，从而发挥其抗菌活性。实时 qPCR 分析表明，两种菌株中与抗菌耐药性和细胞黏附相关的基因表达下调。此外，3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定表明，AgNPs@Pol 对 MCF-7、MG-63 和 NIH-3T3 细胞系的细胞毒性较低。
所开发的 AgNPs@Pol 表现出广泛的胶体稳定性、对 MRSA 和 MSSA 具有强大的抗菌活性和与甲氧西林的协同作用。在原代细胞和体内模型中的进一步研究可能会验证其在临床应用中的潜力。
