Bacteriophage-Loaded Poly(lactic-co-glycolic acid) Microparticles Mitigate Staphylococcus aureus Infection and...

Area of Science:

• Biomaterials Science
• Infectious Diseases
• Microbiology

Background:

• Lung infections from Staphylococcus aureus and Pseudomonas aeruginosa are difficult to treat, exacerbated by antibiotic resistance.
• Bacteriophage (phage) therapy offers an alternative, but effective lung delivery remains a challenge.
• Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polyester with potential for drug delivery.

Purpose of the Study:

• To engineer and evaluate porous PLGA microparticles for effective bacteriophage delivery to the lung.
• To assess the antimicrobial efficacy of phage-loaded microparticles (phage-MPs) against S. aureus and P. aeruginosa.
• To determine the safety and efficacy of phage-MPs in treating bacterial lung infections.

Main Methods:

• Porous microparticles were fabricated from PLGA to encapsulate bacteriophages.
• Phage-loaded microparticles (phage-MPs) were tested for antimicrobial activity against S. aureus and P. aeruginosa in vitro and in vivo.
• Efficacy was assessed in coinfection models and in the presence of cystic fibrosis patient sputum supernatant.
• Cytocompatibility with human lung epithelial cells was evaluated.

Main Results:

• Phage-MPs demonstrated potent in vitro and in vivo antimicrobial efficacy against S. aureus.
• Phage-MPs inhibited S. aureus growth in cystic fibrosis sputum supernatant.
• Co-cultures of S. aureus and P. aeruginosa were effectively mitigated by phage-MPs in vitro.
• Phage-MPs exhibited excellent cytocompatibility with human lung epithelial cells.

Conclusions:

• Porous PLGA microparticles are a viable platform for bacteriophage delivery to the lung.
• Phage-MPs show significant promise for treating S. aureus and polymicrobial lung infections.
• This approach offers a potential new therapeutic strategy against antibiotic-resistant bacterial lung infections.