Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi 75270, Pakistan.
Food and Feed Safety Laboratory, Food and Marine Resources Research Centre, PCSIR Laboratories Complex, Karachi, Sindh 74200, Pakistan.
Int J Nanomedicine. 2020 Oct 13;15:7841-7859. doi: 10.2147/IJN.S274987. eCollection 2020.
The present study reports chitosan functionalized green synthesized CS-AgNPs, conjugated with amoxicillin (AMX), cefixime (CEF), and levofloxacin (LVX) for safe and enhanced antibacterial activity.
The CS-AgNPs and conjugates CS-AgNPs+AMX CS-AgNPs+CEF, and CS-AgNPs+LVX were characterized by UV-Vis, FTIR, SEM, TEM, EDX spectroscopy. The size distribution and zeta potential were measured using the dynamic light scattering (DLS) technique. The interaction between CS-AgNPs and antibiotic molecules was also investigated using UV-Vis spectroscopy at the concentrations of 5, 50, 500, and 5000 µM for each antibiotic. Antibacterial activity and synergism were assessed by the Fractional Inhibitory Concentration (FIC) index. The mechanism for synergistic activity was investigated by the detection of hydroxyl species based on the chemiluminescence of luminol. The biocompatibility index (BI) was calculated from IC using the HeLa cell line. In vivo toxicity and tissue distribution of silver ions were evaluated on Sprague Dawley rats. Physical interactions of antibiotics and significant (P<0.05) antibacterial activity were observed after loading on CS-AgNPs surfaces.
The spherical shape nanocomposites of CS-AgNPs with different antibiotics were prepared with mean size ranges of 80-120 nm. IC of antibiotics-conjugated CS-AgNPs decreased compared to CS-AgNPs. The biocompatibility (BI) index showed that antibiotics-conjugated CS-AgNPs have high antibacterial potential and low toxicity. Highly significant (P<0.005) increase in the generation of hydroxyl species indicated the radical scavenging mechanism for synergistic activity of CS-AgNPs after combined with different antibiotics. Biochemical analysis and histopathological examinations confirmed low toxicity with minor hepatotoxicity at higher doses. After oral administration, extensive distribution of Ag ion was observed in spleen and liver.
The study demonstrates positive attributes of antibiotics-conjugated CS-AgNPs, as a promising antibacterial agent with low toxicity.
本研究报道了壳聚糖功能化绿色合成的 CS-AgNPs，与阿莫西林（AMX）、头孢克肟（CEF）和左氧氟沙星（LVX）缀合，以实现安全和增强的抗菌活性。
通过紫外-可见光谱、傅里叶变换红外光谱、扫描电子显微镜、透射电子显微镜和能谱分析对 CS-AgNPs 和缀合物 CS-AgNPs+AMX、CS-AgNPs+CEF 和 CS-AgNPs+LVX 进行了表征。使用动态光散射（DLS）技术测量了粒径分布和zeta 电位。还通过紫外-可见光谱研究了 CS-AgNPs 与抗生素分子在 5、50、500 和 5000µM 每个抗生素浓度下的相互作用。通过分数抑菌浓度（FIC）指数评估抗菌活性和协同作用。通过基于鲁米诺化学发光检测羟基的方法研究协同活性的机制。通过使用 HeLa 细胞系从 IC 计算生物相容性指数（BI）。在 Sprague Dawley 大鼠上评估银离子的体内毒性和组织分布。在 CS-AgNPs 表面负载抗生素后，观察到抗生素与纳米复合材料之间存在物理相互作用和显著的（P<0.05）抗菌活性。
制备了具有 80-120nm 平均粒径范围的不同抗生素的 CS-AgNPs 球形纳米复合材料。与 CS-AgNPs 相比，抗生素缀合的 CS-AgNPs 的 IC 降低。生物相容性（BI）指数表明，抗生素缀合的 CS-AgNPs 具有高抗菌潜力和低毒性。羟基生成显著增加（P<0.005）表明 CS-AgNPs 与不同抗生素结合后具有协同活性的自由基清除机制。生化分析和组织病理学检查证实，在较高剂量下具有轻微的肝毒性，但毒性较低。口服给药后，观察到 Ag 离子在脾和肝中广泛分布。
该研究表明，抗生素缀合的 CS-AgNPs 具有作为低毒性的有前途的抗菌剂的积极属性。
