中文摘要：介孔二氧化硅纳米颗粒（MSNs）是一种前景很好的抗感染药物纳米载体。许多研究都集中在评估MSNs以可控方式包埋和释放抗生素的能力上，而很少有人关注纳米系统在整个释放期间所释放的影响生物膜的有效抗生素剂量。本文系统、定量研究了从MSNs释放的抗生素对革兰氏阳性和革兰氏阴性细菌生物膜的直接影响。分别将左氧氟沙星(LVX)、庆大霉素(GM)和利福平(RIF)装入纯二氧化硅和氨基修饰的MSNs，这也显示了该纳米系统的多功能性，它们能够装载和释放不同化学性质的抗生素分子；通过测定两种菌株释放的抗生素的生物活性曲线，计算出影响细菌生物膜有效的活性剂量；并在不同时间对成骨样细胞进行体外生物相容性测定。结果发现，在初始阶段，由于抗生素的释放，细胞活力略有下降，但也证明了纳米系统的生物相容性，因为72小时后，细胞恢复了活力；MSNs释放的GM生物活性曲线呈现持续模式，抗生素剂量在2-6 mu g/mL范围内可达100 h，不足以根除生物膜；而LVX和RIF的一阶动力学特征表现为初始爆发效应，随后持续释放超过最低抑制浓度(MIC)达96小时，该剂量可减少99.9%的细菌生物膜，并保持活性72小时，而不会出现细菌耐药性。这项前瞻性的研究为设计MSNs个性化纳米疗法治疗慢性骨感染带来了希望。
外文摘要：Mesoporous silica nanoparticles (MSNs) are promising drug nanocarriers for infection treatment. Many investigations have focused on evaluating the capacity of MSNs to encapsulate antibiotics and release them in a controlled fashion. However, little attention has been paid to determine the antibiotic doses released from these nanosystems that are effective against biofilm during the entire release time. Herein, we report a systematic and quantitative study of the direct effect of the antibiotic-cargo released from MSNs on Gram-positive and Gramnegative bacterial biofilms. Levofloxacin (LVX), gentamicin (GM) and rifampin (RIF) were separately loaded into pure-silica and amino-modified MSNs. This accounts for the versatility of these nanosystems since they were able to load and release different antibiotic molecules of diverse chemical nature. Biological activity curves of the released antibiotic were determined for both bacterial strains, which allowed to calculate the active doses that are effective against bacterial biofilms. Furthermore, in vitro biocompatibility assays on osteoblast-like cells were carried out at different periods of times. Albeit a slight decrease in cell viability was observed at the very initial stage, due to the initial burst antibiotic release, the biocompatibility of these nanosystems is evidenced since a recovery of cell viability was achieved after 72 h of assay. Biological activity curves for GM released from MSNs exhibited sustained patterns and antibiotic doses in the 2-6 mu g/mL range up to 100 h, which were not enough to eradicate biofilm. In the case of LVX and RIF first-order kinetics featuring an initial burst effect followed by a sustained release above the minimum inhibitory concentration (MIC) up to 96 h were observed. Such doses reduced by 99.9% bacterial biofilm and remained active up to 72 h with no emergence of bacterial resistance. This pioneering research opens up promising expectations in the design of personalized MSNs-based nano therapies to treat chronic bone infection.
外文关键词：Antibiotic-cargo；Biofilm；Biological activity curves；Mesoporous silica；nanoparticles
作者：Aguilar-Colomer, A；Colilla, M；Izquierdo-Barba, I；Jimenez-Jimenez, C；Mahillo, I；Esteban, J；Vallet-Regi, M
作者单位：Univ Complutense Madrid；CIBER BBN；IIS Fdn Jimenez Diaz
期刊名称：MICROPOROUS AND MESOPOROUS MATERIALS
期刊影响因子：4.551
出版年份：2021
出版刊次：311
点击下载：介孔二氧化硅纳米颗粒包埋抗生素对革兰氏阳性和革兰氏阴性细菌生物膜的影响