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

J Biomater Sci Polym Ed. 2012;23(18):2321-36. doi: 10.1163/156856211X616183. Epub 2012 May 11.

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; biofilms; implant; magnetic nanoparticles; targeted drug delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Biocompatible Materials / adverse effects*
  • Dose-Response Relationship, Drug
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Drug Liberation
  • Gentamicins / chemistry
  • Gentamicins / pharmacology
  • Gentamicins / toxicity
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / toxicity
  • Materials Testing
  • Prosthesis-Related Infections / chemically induced*
  • Prosthesis-Related Infections / drug therapy*
  • Staphylococcus aureus / drug effects

Substances

  • Anti-Bacterial Agents
  • Biocompatible Materials
  • Drug Carriers
  • Gentamicins
  • Magnetite Nanoparticles