Antimicrobial-loaded biodegradable nanoemulsions for efficient clearance of intracellular pathogens in bacterial...

Area of Science:

• Nanomedicine
• Microbiology
• Immunology

Background:

• Intracellular bacteria pose treatment challenges due to host cell invasion and multidrug resistance (MDR).
• Standard antibiotics are often ineffective against intracellular pathogens, necessitating novel therapeutic strategies.

Purpose of the Study:

• To develop and evaluate a non-antibiotic strategy using phytochemical-loaded biodegradable nanoemulsions (BNEs) for treating intracellular bacterial infections.
• To assess the efficacy of eugenol-loaded BNEs (E-BNEs) against intracellular bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA).

Main Methods:

• Fabrication of polymer-stabilized biodegradable nanoemulsions (BNEs) loaded with antimicrobial phytochemicals.
• Evaluation of E-BNEs for antimicrobial efficacy, macrophage targeting, biocompatibility, and mechanism of cellular entry (cholesterol-dependent membrane fusion).
• Assessment of E-BNEs in a murine model of MRSA-induced peritonitis and evaluation for resistance selection.

Main Results:

• Eugenol-loaded BNEs (E-BNEs) demonstrated superior antimicrobial activity, macrophage accumulation, and biocompatibility.
• E-BNEs facilitated eugenol entry into macrophages via cholesterol-dependent membrane fusion, effectively killing intracellular MRSA.
• E-BNEs reversed MRSA-induced immunosuppression, did not induce resistance, and achieved 99% bacterial clearance in a peritonitis model, outperforming vancomycin.

Conclusions:

• Biodegradable nanoemulsions offer a promising non-antibiotic platform for delivering antimicrobial phytochemicals to treat intracellular infections.
• E-BNEs represent a potent strategy for combating MDR intracellular pathogens and show significant therapeutic potential for peritonitis and other refractory infections.