Silver-loaded nanotubular structures enhanced bactericidal efficiency of antibiotics with synergistic effect in vitro and in vivo

Abstract

Antibiotic-resistant bacteria have become a major issue due to the long-term use and abuse of antibiotics in treatments in clinics. The combination therapy of antibiotics and silver (Ag) nanoparticles is an effective way of both enhancing the antibacterial effect and decreasing the usage of antibiotics. Although the method has been proved to be effective in vitro, no in vivo tests have been carried out at present. Herein, we described a combination therapy of local delivery of Ag and systemic antibiotics treatment in vitro in an infection model of rat. Ag nanoparticle-loaded TiO 2 nanotube (NT) arrays (Ag-NTs) were fabricated on titanium implants for a customized release of Ag ion. The antibacterial properties of silver combined with antibiotics vancomycin, rifampin, gentamicin, and levofloxacin, respectively, were tested in vitro by minimum inhibitory concentration (MIC) assay, disk diffusion assay, and antibiofilm formation test. Enhanced antibacterial activity of combination therapy was observed for all the chosen bacterial strains, including gram-negative Escherichia coli (ATCC 25922), gram-positive Staphylococcus aureus (ATCC 25923), and methicillin-resistant Staphylococcus aureus (MRSA; ATCC 33591 and ATCC 43300). Moreover, after a relative short (3 weeks) combinational treatment, animal experiments in vivo further proved the synergistic antibacterial effect by X-ray and histological and immunohistochemical analyses. These results demonstrated that the combination of Ag nanoparticles and antibiotics significantly enhanced the antibacterial effect both in vitro and in vivo through the synergistic effect. The strategy is promising for clinical application to reduce the usage of antibiotics and shorten the administration time of implant-associated infection.

<p>Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO₂ Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy</p>

“…Besides, Figure 1F showed the release kinetics of Ag + ions from Ag@TiO 2 -NTs detected by ICP-AES on days 1, 3, 5, 7 and 10 was 0.202, 0.046, 0.012, 0.009, and 0.005 ppm, respectively, which decreased gradually after the first 3 days. As with the initial concentration and release kinetics of Ag + ions in our previous study, 10 our Ag@TiO 2 -NTs could have the excellent antibacterial effect when combined with antibiotics. Meanwhile, the size of AgNPs is an important factor that influences the cytotoxicity.…”

“…9,11 For this method, the concentration of the silver salt plays a very important role for both the size and the shape of AgNPs which can be regulated by changing the concentration of AgNO 3 solution. 10,47 Therefore, the size of AgNPs always be around 20 nm for the reason that the concentration of the AgNO 3 solution was 1M.…”

“…8,9 Besides, Ag@TiO 2 -NTs with a lower initial concentration (0.14ppm) of Ag + ions also achieved an excellent synergistic antibacterial capacity in combination with antibiotics both in vitro and in vivo. 10 Interestingly, it has recently been reported that the AgNPs-loaded biomaterials with continuing releasing extremely low dose Ag + could enhance cell adhesion, 10 spreading, 11 proliferation, 12 reactive oxygen species (ROS) scavenging, 11 and new bone formation 13 by the unique controlled-release characteristic and topographic feature.…”

Metallic Antibacterial Surface Treatments of Dental and Orthopedic Materials

“…There were also studies using systemic antibiotics treatment and local delivery of AgNPs in vitro and in vivo. The results indicated that AgNPs increased antibacterial efficiency of antibiotics, reduced their usage of and shortened their administration time [ 107 , 108 ]. On the other hand, metal ions, such as Cu and Zn ions, could also act as environmental drivers of antibiotic resistance via co-occurrence of metal resistance and antibiotic resistance genes in animal isolates of multidrug-resistant bacteria [ 109 , 110 ].…”

<p>Long-lasting bactericidal activity through selective physical puncture and controlled ions release of polydopamine and silver nanoparticles&ndash;loaded TiO_2&nbsp;nanorods in vitro and in vivo</p>

“…Since the biofilms are the physical barriers, which is composed by a three-dimension extracellular polymeric matrix, to protect the inside bacteria from attack by host defense and antibiotics 5. As a result, 1,000-fold higher antibiotic dosage and extended antibiotic therapy may be required to kill the bacteria in biofilm than the common planktonic bacteria, especially for the antibiotics-resistant bacteria strain like methicillin-resistant Staphylococcus aureus (MRSA), etc 6,7. Therefore, it is an urgent issue to inhibit the formation of biofilm at the earliest step by using physical and/or chemical methods 8.…”