pH/Hyal-responsive vancomycin-loaded chitooligosaccharide nanoparticles for intracellular MRSA infection treatment

Area of Science:

• Nanomedicine
• Infectious Diseases
• Pharmacology

Background:

• Staphylococcus aureus (S. aureus) is a critical global pathogen, with intracellular infections posing significant therapeutic challenges due to limited antibiotic penetration.
• Efficient eradication of intracellular S. aureus within macrophages is essential for successful treatment.
• Current antibiotics often struggle to reach intracellular pathogens, necessitating advanced delivery systems.

Purpose of the Study:

• To engineer an active-targeting antibiotic carrier for enhanced intracellular delivery of vancomycin.
• To develop hyaluronic acid-coated chitooligosaccharide nanoparticles (HA/COS@Van) for targeted delivery to macrophages.
• To evaluate the efficacy of HA/COS@Van against intracellular Staphylococcus aureus infections.

Main Methods:

• Fabrication of vancomycin-loaded chitooligosaccharide nanoparticles coated with hyaluronic acid (HA/COS@Van).
• In vitro assessment of nanoparticle uptake in S. aureus-infected macrophages using confocal laser scanning microscopy and flow cytometry.
• In vivo evaluation of nanoparticle biodistribution and therapeutic efficacy in mouse infection models (peritonitis and organ infection).

Main Results:

• HA/COS nanoparticles demonstrated effective accumulation in S. aureus-infected macrophages in vitro.
• Intravenous administration of HA/COS resulted in increased accumulation in the liver, a key site for infected macrophages, in vivo.
• HA/COS@Van exhibited superior in vitro killing of intracellular methicillin-resistant S. aureus (MRSA) compared to free vancomycin.
• HA/COS@Van showed enhanced bactericidal activity in mouse models of acute peritonitis and organ infection.

Conclusions:

• Hyaluronic acid coating enhances nanoparticle biocompatibility and enables active targeting of macrophages via CD44 receptor interaction.
• The HA/COS@Van system demonstrates effective in vitro and in vivo targeting of intracellular S. aureus.
• This active-targeting nanoparticle delivery system holds significant promise for improving therapeutic outcomes against intracellular bacterial pathogens.