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Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal

Inês Santos Ferreira1, Ana F Bettencourt1, Lídia M D Gonçalves1

  • 1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.

International Journal of Nanomedicine
|July 18, 2015
PubMed

Insights

Novel daptomycin-loaded poly-epsilon-caprolactone (PCL) microparticles show enhanced antibiofilm activity against Staphylococcus aureus and Staphylococcus epidermidis biofilms. These biocompatible microparticles offer sustained drug release and potential for treating persistent bacterial infections.

Area of Science:

  • Biomaterials Science
  • Drug Delivery Systems
  • Infectious Diseases

Background:

  • Mature bacterial biofilms pose a significant challenge in treating persistent infections.
  • Antibiotic resistance, particularly in strains like methicillin-resistant Staphylococcus aureus (MRSA), necessitates novel therapeutic strategies.
  • Developing effective drug delivery systems is crucial for enhancing antimicrobial efficacy against biofilms.

Purpose of the Study:

  • To develop daptomycin-loaded poly-epsilon-caprolactone (PCL) microparticles for enhanced antibiofilm activity.
  • To evaluate the efficacy of these microparticles against mature biofilms of MRSA and Staphylococcus epidermidis.
  • To compare the performance of daptomycin-loaded PCL microparticles with vancomycin formulations.

Main Methods:

  • Daptomycin was encapsulated into PCL microparticles using a double emulsion-solvent evaporation method.
  • Characterization included particle morphology, size, encapsulation efficiency, surface charge, thermal behavior, and in vitro drug release kinetics.
  • Antibacterial activity against planktonic and sessile bacteria, as well as mature biofilms, was assessed using isothermal microcalorimetry and fluorescence in situ hybridization.
  • Biocompatibility was evaluated using L929 fibroblasts and MG63 osteoblast-like cells.

Main Results:

  • Daptomycin-loaded PCL microparticles exhibited sustained release of the drug above the minimal inhibitory concentration for up to 72 hours.
  • These microparticles demonstrated superior antibacterial activity against planktonic MRSA and S. epidermidis compared to vancomycin formulations.
  • Significant reduction in MRSA biofilms was observed, with inhibition of S. epidermidis biofilms, and notable microparticle attachment to biofilms.
  • All tested formulations were found to be biocompatible with relevant cell lines.

Conclusions:

  • Daptomycin-loaded PCL microparticles represent a promising strategy for combating MRSA and S. epidermidis biofilms.
  • The sustained release and enhanced antibiofilm activity of these microparticles offer a potential therapeutic advantage.
  • Further investigation into their clinical application for treating biofilm-associated infections is warranted.
Keywords:
Staphylococcus aureusStaphylococcus epidermidisantibiotic releasefluorescence in situ hybridizationisothermal microcalorimetry

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