A New Antibiotic-Loaded Sol-Gel Can Prevent Bacterial Prosthetic Joint Infection: From in vitro Studies to an in vivo Model

Abstract

The aim of this study was to evaluate the effect of a moxifloxacin-loaded organicinorganic sol-gel with different antibiotic concentration in the in vitro biofilm development and treatment against Staphylococcus aureus, S. epidermidis, and Escherichia coli, cytotoxicity and cell proliferation of MC3T3-E1 osteoblasts; and its efficacy in preventing the prosthetic joint infection (PJI) caused by clinical strains of S. aureus and E. coli using an in vivo murine model. Three bacterial strains, S. epidermidis ATCC 35984, S. aureus 15981, and, E. coli ATCC 25922, were used for microbiological studies. Biofilm formation was induced using tryptic-soy supplemented with glucose for 24 h, and then, adhered and planktonic bacteria were estimated using drop plate method and absorbance, respectively. A 24-h-mature biofilm of each species growth in a 96well plate was treated for 24 h using a MBECTM biofilm Incubator lid with pegs coated with the different types of sol-gel, after incubation, biofilm viability was estimated using alamrBlue. MC3T3-E1 cellular cytotoxicity and proliferation were evaluated using CytoTox 96 Non-Radioactive Cytotoxicity Assay and alamarBlue, respectively. The microbiological studies showed that sol-gel coatings inhibited the biofilm development and treated to a mature biofilm of three evaluated bacterial species. The cell studies showed that the sol-gel both with and without moxifloxacin were non-cytotoxic and that cell proliferation was inversely proportional to the antibiotic concentration containing by sol-gel. In the in vivo study, mice weight increased over time, except in the E. coliinfected group without coating. The most frequent symptoms associated with infection were limping and piloerection; these symptoms were more frequent in infected groups

A New Antibiotic-Loaded Sol-Gel can Prevent Bacterial Intravenous Catheter-Related Infections

“…The antibacterial activity of moxifloxacin-loaded sol-gel is a fruit of moxifloxacin release resulting from hydrolytic degradation of organic-inorganic sol-gel [11] during its hydration in contact with systemic fluids [12]. Sol-gel degradation in physiologic conditions gives rise to different debris and/or silica-derivate molecular components from sol-gel, which may interact with the blood, causing coagulation complications, or with the walls of the veins with which the catheter is in contact.…”

“…Moxifloxacin (Sigma Aldrich, Saint Louis, MO, USA) dissolved in water was added at a concentration of 50 mg per 20.3 mL of sol-gel (A50). This concentration has been intentionally chosen because it represents the maximum amount of antibiotic which sol-gel can contain without compromising its stability, durability and adherence to titanium substrates [11]. The physicochemical characterization of sol-gel has already been previously described [12].…”

“…The physicochemical characterization of sol-gel has already been previously described [12]. The moxifloxacin release rate from a moxifloxacin sol-gel under physiological conditions was 120 ng/h [11].…”

“…Antimicrobial catheter strategies which go beyond the impregnation method are less common; however, it is worth emphasizing catheters made of polyurethane supersaturated with molecularly dispersed rifampin and miconazole [10]. Recently, we demonstrated that a moxifloxacin-loaded organic-inorganic sol-gel is able to locally prevent the prosthetic joint infection provoked by both Gram-positive and Gram-negative bacteria [11]. This antibacterial activity is a result of the hydrolytic degradation of organic-inorganic sol-gel [12], which favors a lineal release of moxifloxacin from the material [11].…”

“…Recently, we demonstrated that a moxifloxacin-loaded organic-inorganic sol-gel is able to locally prevent the prosthetic joint infection provoked by both Gram-positive and Gram-negative bacteria [11]. This antibacterial activity is a result of the hydrolytic degradation of organic-inorganic sol-gel [12], which favors a lineal release of moxifloxacin from the material [11]. Sol-gel technology is a versatile tool, with an easy, environmentally friendly and low-energy-consuming procedure, which, unlike other synthesis processes to obtain organic polymer coatings [13,14], does not involve performing several procedural steps nor pretreatment of the biomaterial surface [12,15].…”