A Novel Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections

Abstract

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Owing to the presence of implants and the formation of bacterial biofilms, the efficacy of antibiotics is limited. Furthermore, osteoclasts can become extremely active, accompanied by bone loss in the infected microenvironment. Therefore, implants often need to be removed. To improve the concentrations of antibiotics in bony tissues and enhance their effectiveness in preventing bacterial biofilm formation, the infection rate must be controlled to preserve the implants. Enoxacin exerts combined antibacterial and osteoclast inhibitory effects. It also plays a role in limiting infections and preventing bone loss. Aspartic acid octapeptide (ASP8) can also recognize and combine with hydroxyapatite crystals in bones and can be targeted to increase antibiotic concentrations in bones. Our previous research showed that preparing mesoporous nanomaterials resulted in optimal drug loading, releasing, and bone-targeting properties. Based on earlier research, a new bone-targeted antibiotic release system was developed. Enoxacin and ASP8 were loaded on mesoporous silica nanoparticles (MSNs) to increase antibiotic concentrations, prevent bacterial biofilm formation, inhibit aberrant osteoclast activities, and reduce bone loss. Enoxacin-loaded MSNs (Gen@MSN-D) were assessed using a variety of experimental methods, including rat models. We studied the in vitro antibacterial properties of the new drug delivery system. We found that these materials had antibacterial properties in vivo, inhibitory effects on osteoclasts, and can be used to prevent and treat post-implantation infections and bone loss. Therefore, we believe these materials will provide a new method for preventing and treating post-operative, orthopaedic implant-associated infections.