Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Microbiology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
Arch Microbiol. 2023 Mar 8;205(4):109. doi: 10.1007/s00203-023-03447-6.
The present study aimed to prepare and characterize vancomycin-loaded mesoporous silica nanoparticles (Van-MSNs) to detect inhibitory effects on the planktonic and biofilm forms of methicillin-resistant Staphylococcus aureus (MRSA) isolates, and study the biocompatibility and toxicity of Van-MSNs in vitro as well as antibacterial activity of Van-MSNs against Gram-negative bacteria. The inhibitory effects of Van-MSNs were investigated on MRSA using the determination of minimum inhibitory (MIC) and minimum biofilm-inhibitory concentrations (MBIC) as well as the effect on bacterial attachment. Biocompatibility was studied by examining the effect of Van-MSNs on the lysis and sedimentation rate of red blood cells (RBC). The interaction of Van-MSNs with human blood plasma was detected by the SDS-PAGE approach. The cytotoxic effect of the Van-MSNs on human bone marrow mesenchymal stem cells (hBM-MSCs) was evaluated by the MTT assay. The antibacterial effects of vancomycin and Van-MSNs on Gram-negative bacteria were also investigated using MIC determination using the broth microdilution method. Furthermore, bacteria outer membrane (OM) permeabilization was determined. Van-MSNs showed inhibitory effects on planktonic and biofilm forms of bacteria on all isolates at levels lower than MICs and MBICs of free vancomycin, but the antibiofilm effect of Van-MSNs was not significant. However, Van-MSNs did not affect bacterial attachment to surfaces. Van-loaded MSNs did not show a considerable effect on the lysis and sedimentation of RBC. A low interaction of Van-MSNs was detected with albumin (66.5 kDa). The hBM-MSCs viability in exposure to different levels of Van-MSNs was 91-100%. MICs of ≥ 128 µg/mL were observed for vancomycin against all Gram-negative bacteria. In contrast, Van-MSNs exhibited modest antibacterial activity inhibiting the tested Gram-negative bacterial strains, at concentrations of ≤ 16 µg/mL. Van-MSNs increased the OM permeability of bacteria that can increase the antimicrobial effect of vancomycin. According to our findings, Van-loaded MSNs have low cytotoxicity, desirable biocompatibility, and antibacterial effects and can be an option for the battle against planktonic MRSA.
本研究旨在制备和表征载万古霉素介孔硅纳米颗粒（Van-MSNs），以检测其对耐甲氧西林金黄色葡萄球菌（MRSA）分离株浮游和生物膜形式的抑制作用，并研究 Van-MSNs 的体外生物相容性和毒性以及其对革兰氏阴性菌的抗菌活性。使用最低抑菌浓度（MIC）和最低生物膜抑制浓度（MBIC）的测定以及对细菌附着的影响来研究 Van-MSNs 对 MRSA 的抑制作用。通过检查 Van-MSNs 对红细胞（RBC）裂解和沉降率的影响来研究生物相容性。通过 SDS-PAGE 方法检测 Van-MSNs 与人血浆的相互作用。通过 MTT 测定评估 Van-MSNs 对人骨髓间充质干细胞（hBM-MSCs）的细胞毒性作用。使用肉汤微量稀释法测定 MIC 还研究了万古霉素和 Van-MSNs 对革兰氏阴性菌的抗菌作用。此外，还测定了细菌外膜（OM）通透性。Van-MSNs 在所有分离株中，在低于游离万古霉素的 MIC 和 MBIC 水平下，对浮游和生物膜形式的细菌均表现出抑制作用，但 Van-MSNs 的抗生物膜作用并不显著。然而，Van-MSNs 并不影响细菌对表面的附着。载万古霉素的 MSNs 对 RBC 的裂解和沉降没有明显影响。检测到 Van-MSNs 与白蛋白（66.5 kDa）的相互作用较低。在暴露于不同水平的 Van-MSNs 时，hBM-MSCs 的存活率为 91-100%。对所有革兰氏阴性菌，万古霉素的 MIC 为≥128 µg/mL。相比之下，Van-MSNs 对浓度≤16 µg/mL 的测试革兰氏阴性菌菌株表现出适度的抗菌活性。Van-MSNs 增加了细菌的 OM 通透性，这可以增加万古霉素的抗菌效果。根据我们的发现，载万古霉素的 MSNs 具有低细胞毒性、良好的生物相容性和抗菌作用，并且可以作为对抗浮游性 MRSA 的选择。
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