Gentamicin-Loaded Polysaccharide Membranes for Prevention and Treatment of Post-operative Wound Infections in the Skeletal System

Pharm Res. 2017 Oct;34(10):2075-2083. doi: 10.1007/s11095-017-2212-5. Epub 2017 Jun 21.

Abstract

Purpose: To develop polysaccharide-based membranes that allow controlled and localized delivery of gentamicin for the treatment of post-operative bone infections.

Methods: Membranes made of gellan gum (GUM), sodium alginate (ALG), GUM and ALG crosslinked with calcium ions (GUM + Ca and ALG + Ca, respectively) as well as reference collagen (COL) were produced by freeze-drying. Mechanical properties, drug release, antimicrobial activity and cytocompatibility of the membranes were assessed.

Results: The most appropriate handling and mechanical properties (Young's modulus, E = 92 ± 4 MPa and breaking force, F MAX = 2.6 ± 0.1 N) had GUM + Ca membrane. In contrast, COL membrane showed F MAX = 0.14 ± 0.02 N, E = 1.0 ± 0.3 MPa and was deemed to be unsuitable for antibiotic delivery. The pharmacokinetic data demonstrated a uniform and sustainable delivery of gentamicin from GUM + Ca (44.4 ± 1.3% within 3 weeks), while for COL, ALG and ALG + Ca membranes the most of the drug was released within 24 h (55.3 ± 1.9%, 52.5 ± 1.5% and 37.5 ± 1.8%, respectively). Antimicrobial activity against S. aureus and S. epidermidis was confirmed for all the membranes. GUM + Ca and COL membranes supported osteoblasts growth, whereas on ALG and ALG + Ca membranes cell growth was reduced.

Conclusions: GUM + Ca membrane holds promise for effective treatment of bone infections thanks to favorable pharmacokinetics, bactericidal activity, cytocompatibility and good mechanical properties.

Keywords: alginate; gellan gum; gentamicin; local drug delivery; membranes.

MeSH terms

  • Alginates / chemistry
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Calcium / chemistry
  • Collagen / chemistry
  • Cross-Linking Reagents / chemistry
  • Drug Carriers / chemistry
  • Drug Liberation
  • Gentamicins / administration & dosage
  • Gentamicins / chemistry
  • Gentamicins / pharmacology*
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Humans
  • Materials Testing / methods
  • Membranes, Artificial
  • Osteomyelitis / drug therapy*
  • Osteomyelitis / prevention & control*
  • Polysaccharides / chemistry*
  • Polysaccharides, Bacterial / chemistry
  • Staphylococcus aureus / drug effects
  • Wound Infection / drug therapy
  • Wound Infection / prevention & control

Substances

  • Alginates
  • Anti-Bacterial Agents
  • Cross-Linking Reagents
  • Drug Carriers
  • Gentamicins
  • Hexuronic Acids
  • Membranes, Artificial
  • Polysaccharides
  • Polysaccharides, Bacterial
  • gellan gum
  • Glucuronic Acid
  • Collagen
  • Calcium