Abstract
Cefazolin is an antibiotic frequently used in preoperative prophylaxis of orthopedic surgery and to fight secondary infections post-operatively. Although its systemic delivery in a bulk or bolus dose is usually effective, the local and controlled release can increase its effectiveness by lowering dosages, minimizing total drug exposure, abating the development of antibiotic resistance and avoiding the cytotoxic effect. A delivery system based on mesoporous silicon microparticles was developed that is capable of efficiently loading and continuously releasing cefazolin over several days. The in vitro release kinetics from mesoporous silicon microparticles with three different nanopore sizes was evaluated, and minimal inhibitory concentration of cefazolin necessary to eliminate a culture of Staphylococcus aureus was identified to be 250 µg/mL. A milder toxicity toward mesenchymal stem cells was observed from mesoporous silicon microparticles over a 7-day period. Medium pore size-loaded mesoporous silicon microparticles exhibited long-lasting bactericidal properties in a zone inhibition assay while they were able to kill all the bacteria growing in suspension cultures within 24 h. This study demonstrates that the sustained release of cefazolin from mesoporous silicon microparticles provides immediate and long-term control over bacterial growth both in suspension and adhesion while causing minimal toxicity to a population of mesenchymal stem cell. Mesoporous silicon microparticles offer significant advantageous properties for drug delivery applications in tissue engineering as it favorably extends drug bioavailability and stability, while reducing concomitant cytotoxicity to the surrounding tissues.