Magnetic Drug Targeting as New Therapeutic Option for the Treatment of Biomaterial Infections

Abstract

Implant-associated infections are a challenging problem in surgery. Bacteria in biofilms are difficult to treat as they are less susceptible to antibiotics or antiseptics which require high drug concentrations at the site of infection. We present a novel strategy to concentrate high antibiotic doses systemically at the target site using newly developed antibiotic-functionalized nanoparticles directed by a magnetic drug-targeting system. The important and effective antibiotic gentamicin served as antimicrobial substance and was ionically or covalently attached to magnetic nanoparticles. Subsequently, the particles were characterized thoroughly. Anti-infective properties with regard to Staphylococcus aureus and the degree of cytotoxicity concerning human umbilical vein endothelial cells were determined. The enrichment of the magnetic nanoparticles at the surface of model tubes in circulatory experiments was investigated. We describe a promising technique for the loading of magnetic nanoparticles to treat systemic infections. Gentamicin-coated magnetic nanoparticles reduced bacterial growth even beyond pathologically relevant concentrations within 24 h. Excellent concentration independent biocompatibility was found for the nanoparticles themselves and we demonstrate that the magnetic nanoparticles can be navigated and concentrated on surfaces of model implants using a permanent magnetic field.

Keywords:

• Gentamicin
• implant
• magnetic nanoparticles
• targeted drug delivery
• biofilms

Acknowledgements

We would like to thank Dr.-Ing. B. Gleich for his great assistance in technical questions regarding highly focused magnetic fields and magnetic field forces for targeting. Furthermore we acknowledge Dipl. Wirtsch.-Ing. H. Stephan and Dipl. Phys. W. Kraus (Neue Magnetodyn GmbH) for their technical help, contributions and inspiring discussions. Special thanks to Dr. C. Bergemann (Chemicell GmbH), who kindly provides the TargetMag, FluidMag and SiMag ferrofluids. The authors did not receive any payments or benefits from a commercial party related directly or indirectly to the subject of this article. This work was partially supported by a grant from the Bayerische Forschungsstiftung.