title: Preparation of gentamicin dioctyl sulfosuccinate loaded poly(trimethylene carbonate) matrices intended for the treatment of orthopaedic infections.
abstract: BACKGROUND
  Infection is a common problem in trauma and orthopaedic surgery. Antibiotic-loaded biomaterials are used locally to clear infections as an adjunct to systemic antibiotics. Gentamicin-sulphate (GEN-SULPH) is commonly used in antibiotic-loaded biomaterials, although it displays high water solubility resulting in quick diffusion from the carrier.
  
  
  OBJECTIVE
  Preparation of a lipophilic derivative of gentamicin to reduce solubility and obtain a slower release. Subsequently, entrapment of this lipophilic gentamicin within poly(trimethylene carbonate) (PTMC) matrices.
  
  
  METHODS
  Hydrophobic ion-pairing was used to prepare lipophilic gentamicin (GEN-AOT). The susceptibility of Staphylococcus aureus NCTC 12973 and Staphylococcus epidermidis 103.1 for GEN-AOT was tested and the viability of fibroblasts upon exposure to GEN-AOT was assessed. GEN-AOT was then loaded into PTMC films.
  
  
  RESULTS
  GEN-AOT was successfully prepared as confirmed by FTIR-spectroscopy. GEN-AOT was bactericidal for S. epidermidis and S. aureus at 0.5 μM and 8.5 μM, respectively. At 1.1 μM GEN-AOT no reduction in fibroblast viability was observed. At 11 μM the reduction was ∼50% . PTMC discs loaded with GEN-AOT were prepared by compression molding.
  
  
  CONCLUSIONS
  Lipophilic GEN-AOT was at least as potent as GEN-SULPH. For S. epidermidis it was even more potent than GEN-SULPH. More than 50% fibroblast cell viability was maintained at bactericidal concentration for both bacterial strains.
authors.affiliation: AO Research Institute Davos, Davos-Platz, Switzerland.|Department of Biomaterials Science & Technology, University of Twente, Enschede, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: ter Boo
authors.affiliation: Department of Biomaterials Science & Technology, University of Twente, Enschede, The Netherlands.|University of Groningen, University Medical Center Groningen, W.J. Kolff Institute, Department of Biomedical Engineering, Groningen, The Netherlands.
authors.forename: D W
authors.initials: DW
authors.lastname: Grijpma
authors.affiliation: AO Research Institute Davos, Davos-Platz, Switzerland.
authors.forename: R G
authors.initials: RG
authors.lastname: Richards
authors.affiliation: AO Research Institute Davos, Davos-Platz, Switzerland.
authors.forename: T F
authors.initials: TF
authors.lastname: Moriarty
authors.affiliation: AO Research Institute Davos, Davos-Platz, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Eglin
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry*; D004146:Dioxanes / Q000737:chemistry*; D004343:Drug Implants; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005839:Gentamicins / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D011108:Polymers / Q000737:chemistry*; D019736:Prostheses and Implants; D013210:Staphylococcus / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D004146:Dioxanes; D004343:Drug Implants; D005839:Gentamicins; D011108:Polymers; D004143:Dioctyl Sulfosuccinic Acid; C059299:polytrimethylene carbonate
keywords: Orthopaedic infection; antibiotic modification; drug delivery; gentamicin; local infection treatment; poly(trimethylene carbonate)