Biphasic mode of antibacterial action of aminoglycoside antibiotics-loaded elastic hydroxyapatite-glucan composite

Int J Pharm. 2013 Sep 15;454(1):285-95. doi: 10.1016/j.ijpharm.2013.06.076. Epub 2013 Jul 9.

Abstract

Following the quest for new composite materials for bone tissue engineering, a novel elastic hydroxyapatite-glucan composite loaded with two aminoglycoside antibiotics was prepared. The porosity of the composite and the drug release profiles in closed-loop and semi-open systems were tested. The antibacterial activity of the drug was estimated against two Gram-positive and two Gram-negative bacterial strains causing orthopedic infections. It was found that the loaded antibiotic acted in a biphasic mode. The majority of the drug was released within 48-119 h in a pore-dependent manner and inhibited the bacterial growth in the culture medium. However, a small residual amount of the drug was bound to the composite microstructure via ionic interactions and acted as a short-lived barrier against bacterial adhesion to the composite, although the surrounding medium was no longer protected against bacterial infection. Sub-inhibitory concentrations of the released drug were observed in the medium only during the last two days of the experiment (minimized risk of occurrence of drug-resistant strains). Thus the novel drug-loaded elastic hydroxyapatite-glucan composite, demonstrating a biphasic mode of antibacterial action, may be recommended for antibiotic prophylaxis in bone substitute implantation, with less emphasis on the treatment of bone infections.

Keywords: Amikacin; Bacterial strains; Ceramics; Elastic bone-replacing material; Gentamicin; Multiphasic release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amikacin / chemistry
  • Amikacin / pharmacology*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bone Substitutes*
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Drug Carriers*
  • Durapatite / chemistry*
  • Elasticity
  • Gentamicins / chemistry
  • Gentamicins / pharmacology*
  • Glucans / chemistry*
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / growth & development
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / growth & development
  • Kinetics
  • Porosity
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Technology, Pharmaceutical / methods

Substances

  • Anti-Bacterial Agents
  • Bone Substitutes
  • Delayed-Action Preparations
  • Drug Carriers
  • Gentamicins
  • Glucans
  • Amikacin
  • Durapatite