Rhamnolipid Micelles Assist Azithromycin in Efficiently Disrupting Staphylococcus aureus Biofilms and Impeding Their

Shiyu Lin1, Xiaojuan Li1, Yuning Zhang1

  • 1Innovative Engineering Research Center of Veterinary Pharmaceutics, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People's Republic of China.

PubMed
Abstract

Insights

This study developed azithromycin-loaded rhamnolipid nanomicelles (AZI@RHL) to combat antibiotic-resistant biofilms. AZI@RHL effectively disrupted biofilms, killed bacteria, and prevented regrowth, offering a promising solution for chronic infections.

Area of Science:

  • Biotechnology
  • Materials Science
  • Infectious Diseases

Background:

  • Bacterial biofilms are highly resistant to antibiotics, contributing to over 80% of chronic infections.
  • These persistent infections present a significant medical and economic burden due to their refractory and relapsing nature.

Purpose of the Study:

  • To develop a novel nanomicelle system encapsulating azithromycin (AZI) with rhamnolipid (RHL) for enhanced antibiofilm activity.
  • To investigate the efficacy of the AZI@RHL nanomicelles in disrupting Staphylococcus aureus biofilms and preventing their reformation.

Main Methods:

  • Rhamnolipid (RHL), a biosurfactant, was utilized to load the antibiotic azithromycin (AZI) into stable nanomicelles (AZI@RHL).
  • The antibiofilm efficacy of AZI@RHL was evaluated by measuring biofilm biomass reduction, component degradation (polysaccharides, proteins), and bacterial cell killing rates.
  • Confocal microscopy was used to visualize biofilm structure disruption, and inhibition of biofilm formation was assessed by monitoring cell auto-aggregation and eDNA release.

Main Results:

  • AZI@RHL significantly reduced biofilm biomass by 48.2%, with substantial decreases in polysaccharides (47.5%) and proteins (36.8%).
  • The nanomicelles achieved 48.2% bacterial cell killing within the biofilm, significantly outperforming free AZI (17%) and blank micelles (20%).
  • Biofilm formation was inhibited by up to 92% with AZI@RHL, demonstrating superior efficacy over RHL (27.7%) and free AZI (12%) in preventing regrowth.

Conclusions:

  • Loading azithromycin into rhamnolipid nanomicelles significantly enhances its antibiofilm efficacy.
  • AZI@RHL offers a comprehensive one-step solution for managing biofilms, including disruption, bacterial inactivation, and prevention of recolonization and reformation.

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