Nanoemulsion-based colistin for pulmonary delivery: Enhanced antibacterial efficacy against Acinetobacter baumannii

Area of Science:

• Antimicrobial drug delivery
• Nanotechnology in medicine
• Infectious disease research

Background:

• Acinetobacter baumannii infections, including pneumonia and bacteraemia, pose significant clinical challenges.
• Colistin is a last-resort antibiotic for severe infections but exhibits high toxicity.
• Developing targeted drug delivery systems is crucial to enhance efficacy and reduce side effects.

Purpose of the Study:

• To develop a colistin-loaded nanoformulation (COL-NE) for targeted delivery to infected lung cells.
• To enhance the antibacterial efficacy of colistin against Acinetobacter baumannii.
• To reduce the toxicity associated with colistin therapy.

Main Methods:

• Screening and optimization of colistin nanoemulsion formulations.
• Characterization of nanoemulsion particle size and antimicrobial activity (MIC).
• In vitro assessment of antibiofilm activity, cellular penetration, and toxicity.
• In vivo evaluation in a murine pneumonia model following intratracheal administration.

Main Results:

• An optimized COL-NE with a particle size of 180 nm was developed.
• COL-NE demonstrated a 1-4 fold reduction in MIC against A. baumannii and significant antibiofilm activity.
• In vitro studies showed enhanced cellular penetration and a 27-45% reduction in toxicity compared to free colistin.
• In vivo, COL-NE reduced lung bacterial burden by 2 log₁₀ CFU/mL in a murine pneumonia model.

Conclusions:

• Colistin-loaded nanoemulsions (COL-NE) show potential for targeted therapy against Acinetobacter baumannii infections.
• COL-NE enhances antibacterial efficacy and improves bacterial elimination from infected macrophages.
• This nanoformulation strategy effectively mitigates colistin-associated toxicity, offering a safer therapeutic option.