Functionalized Nanoparticles for the Treatment of Implant-Related or Intracellularly Persistent Infections

In orthopedics, joint replacement is a frequently performed procedure. Knee and hip joints are most commonly affected. Periprosthetic joint infections (PJI) are severe complications and occur in up to 2% of primary joint arthroplasty and even higher rates after implant revision surgery. Requiring long hospitalization periods, long-term antibiotics and often additional revision surgery, PJI is a cost-intensive public health problem. On implant surfaces, the formation of biofilm drastically lowers the accessibility for antibiotics. Staphylococcus aureus (S. aureus) is one of the prevalent biofilm-forming bacteria which plays an important role in PJI and other orthopedic infections like osteomyelitis. Functional silica nanoparticles (SNPs) as a drug-delivery system may enable a sufficient therapeutic concentration also in areas which are commonly difficult to reach like the surface of infected implants. Optimal release kinetics and sufficient concentration in the desired region are key roles for successful application SNPs provide good biocompatibility and high internal pore volume for deposition of therapeutics. They were functionalized with a pH-sensitive polymer and loaded with enrofloxacin (EFX). SNPs were dispersed in PBS and citrate buffer, respectively for 1h, 2h and 3h. Supernatants were collected and stored at −20°C until further evaluation. S. aureus cultures were transferred to a 96-well-plate, and different concentrations of the EFX supernatants were added to the wells. Pure culture media with/without bacteria were evaluated as positive/negative controls. PBS and citrate buffer alone were tested equivalently to identify any influence of the buffers. Well plates were cultured for 24h at 37°C and bacterial growth was evaluated by optical density measurements at 600 nm. An influence of the acidic buffer was visible up to a dilution ratio of 1/40. The performance of both supernatants was similar after 1h with total inhibition of bacterial growth up to a dilution ratio of 1/320. The corresponding EFX concentrations were 0.21 µg/ml and 0.25 µg/ml for neutral and acidic supernatants, respectively. After 2h and 3h, higher dilution ratios showed a better performance of EFX supernatants obtained in acidic medium at 2h and 3h (Fig. 1), corresponding to a higher EFX release from the SNP after 3h. As infected areas commonly show decreased pH values, here tested functionalized SNP might be promising candidates for directed release of antibiotics. Ongoing research currently evaluates their ability to be incorporated by cells like osteoblasts for the treatment of intracellularly hidden bacteria. For any figures or tables, please contact the authors directly.