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Combination Antibiotic Delivery in PMMA Provides Sustained Broad-Spectrum Antimicrobial Activity and Allows for

Erika L Cyphert1, Chao-Yi Lu1, Dylan W Marques1

  • 1Department of Biomedical Engineering , Case Western Reserve University , 10900 Euclid Avenue , Cleveland , Ohio 44106 , United States.

Biomacromolecules
|December 27, 2019
PubMed

Insights

This study introduces a novel combination antibiotic poly(methyl methacrylate) (PMMA) system using drug-filled microparticles. This advanced antimicrobial composite offers extended efficacy and refilling capabilities for treating challenging bone infections.

Area of Science:

  • Biomaterials Science
  • Infectious Disease Research
  • Drug Delivery Systems

Background:

  • Antibiotics in poly(methyl methacrylate) (PMMA) are used for localized infection treatment, but face limitations with chronic/recurrent infections and antibiotic resistance.
  • Current single-drug approaches in PMMA are insufficient for polymicrobial infections, increasing the risk of bacterial resistance.

Purpose of the Study:

  • To develop and evaluate a combination antibiotic PMMA composite system for enhanced antimicrobial efficacy and duration.
  • To investigate the potential for refilling antibiotic-loaded microparticles within the PMMA composite for sustained therapeutic effect.
  • To assess the mechanical properties of the developed composite for potential clinical applications.

Main Methods:

  • Formulation of a novel PMMA composite incorporating rifampicin-filled β-cyclodextrin (β-CD) microparticles and a second antibiotic.
  • Evaluation of antimicrobial activity using zone of inhibition assays and drug release studies.
  • Assessment of refilling capabilities and mechanical properties of the composite materials.

Main Results:

  • The combination antibiotic PMMA composite demonstrated up to an 8-fold increase in antimicrobial activity duration compared to conventional antibiotic-PMMA.
  • The β-cyclodextrin microparticles enabled successful refilling of antibiotics, providing additional therapeutic windows.
  • Tested formulations showed a minor but significant decrease in mechanical properties compared to controls.

Conclusions:

  • The developed combination antibiotic PMMA composite system offers a promising strategy for prolonged and refillable antimicrobial delivery.
  • While mechanical properties require further investigation for load-bearing applications like bone cement, the composite is suitable for non-load-bearing uses such as antimicrobial beads.
  • This innovation addresses limitations of current antibiotic-PMMA strategies, offering improved treatment options for challenging bone infections.

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