Gentamicin extended release from an injectable polymeric implant

J Control Release. 2007 Jan 22;117(1):90-6. doi: 10.1016/j.jconrel.2006.10.010. Epub 2006 Oct 11.

Abstract

Gentamicin sulfate, a potent antibiotic agent, is currently used for treatment of osteomyelitis mainly by intravenous injection with a long-term indwelling catheter, local implant of antibiotic containing polymethylmethacrylate beads or calcium phosphate (bone cements). Searching for more effective treatments, this study was designed to evaluate biodegradable injectable gelling polymeric devices for the controlled release of gentamicin sulfate in the treatment of invasive bacterial infections. Gentamicin sulfate was incorporated in poly(sebacic-co-ricinoleic-ester-anhydride P(SA-RA)) paste at 10-20% w/w and its release in buffer solution was monitored. The in vitro activity of the formulations was determined against Staphylococcus aureus. A constant release of active gentamicin for over 28 days was found. The stability of the formulation was determined under different storage conditions. The formulations were stable to sterilization by gamma-irradiation and long term storage under freezing. The toxicity of the polymer and the formulations with gentamicin was examined by subcutaneous injection to rats. Four weeks after implantation, histopathological examination of the tissues surrounding the implant showed no inflammation. A preliminary study revealed positive effect of gentamicin containing P(SA-RA) on established osteomyelitis in a rat model. In conclusion this study suggests that poly(sebacic-co-ricinoleic-ester-anhydride) 3:7 loaded with 10%-20% gentamicin sulfate, might be used as an injectable biodegradable device for in situ treatment of osteomyelitis induced by S. aureus.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / toxicity
  • Chemistry, Pharmaceutical
  • Decanoic Acids
  • Delayed-Action Preparations
  • Drug Implants
  • Drug Stability
  • Drug Storage
  • Gamma Rays
  • Gentamicins / administration & dosage*
  • Gentamicins / pharmacokinetics
  • Gentamicins / toxicity
  • Injections
  • Male
  • Microbial Sensitivity Tests
  • Molecular Weight
  • Osteomyelitis / drug therapy
  • Osteomyelitis / microbiology
  • Polymers
  • Rats
  • Rats, Wistar
  • Ricinoleic Acids
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects
  • Viscosity

Substances

  • Anti-Bacterial Agents
  • Decanoic Acids
  • Delayed-Action Preparations
  • Drug Implants
  • Gentamicins
  • Poly(sebacic acid-co-ricinoleic acid)
  • Polymers
  • Ricinoleic Acids