Antimicrobial drug LbL-assembled delivery system for orthopaedic nanocomposite bone cements

Abstract

Total joint replacement (TJR) is commonly used for the treatment of end stage arthritis. The use of Poly-methylmethacrylate (PMMA) bone cement is a gold standard TJR, where it is frequently used for local delivery of antibiotics to provide prophylaxis from prosthetic joint infections (PJI). Currently used antibiotic loaded bone cements have many limitations, including burst release which fall below inhibitory levels leading to the selection of antibiotic resistant strains. This study aims to provide a controlled release for antimicrobial agents from bone cement to provide prophylaxis from postsurgical infections. For this purpose, gentamicin and chlorhexidine were loaded alone or in combination on silica nanoparticles surface using layer-by-layer coating technique (LbL). A novel LbL construct was built using hydrolysable and non-hydrolysable polymers. The nanoparticles were characterised by transmission electron microscopy, thermogravimetric analysis, zeta measurement, and drug release in different media. Then, antimicrobial agents LbL coated nanoparticles were incorporated into PMMA cement and the nanocomposite is characterized for drug release, antimicrobial, mechanical, rheological properties and cytocompatibility. The build-up of LbL coating was confirmed by thermogravimetric analysis and zeta measurements. The release of antimicrobial agents was controlled for > 30 days for different drugs used. The nanocomposite drug release profile also continued > 30 days at concentration higher than the commercial formula t ion containing the same amount of antibiotics, where burst release for few days were observed. Moreover, the nanocomposite showed superior antimicrobial inhibit ion for bacterial growth, without adversely affecting the mechanical properties. Different nanocomposites showed cytocompatibility when tested against Saos-2 cells. Techniques from a variety of disciplines were employed in this study and this interdisciplinary approach has allowed many features of PMMA bone cement to be investigated. The developed nanocomposites can have the potential to reduce PJIs, and the newly developed LbL nano-delivery system may have wider application in a variety of biomaterials