Tailored Levofloxacin Incorporated Extracellular Matrix Nanoparticles for Pulmonary Infections

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pulmonary Medicine

Background:

• Cystic fibrosis (CF) involves viscous lung mucus, increasing susceptibility to bacterial infections like *Pseudomonas aeruginosa* and *Staphylococcus aureus*.
• These common CF pathogens are often antibiotic-resistant, necessitating novel therapeutic strategies.
• Levofloxacin (LVX) is an antibiotic used for these infections, but its delivery can be improved.

Purpose of the Study:

• To develop and evaluate hybrid nanoparticles combining levofloxacin (LVX) and extracellular matrix (ECM) for enhanced pulmonary delivery in cystic fibrosis.
• To assess the potential of these nanoparticles to overcome the mucus barrier and effectively treat bacterial lung infections in CF.

Main Methods:

• Formulation of hybrid nanoparticles with LVX and ECM in 10:1 and 1:1 ratios.
• Characterization of nanoparticle surface charge, size, and drug dissolution profiles.
• In vitro assessment of nanoparticle toxicity to human airway epithelial cells and efficacy against *Pseudomonas aeruginosa* and *Staphylococcus aureus*.

Main Results:

• Two hybrid formulations exhibited neutral surface charges and average sizes of ~525 nm (10:1) and ~300 nm (1:1).
• Nanoparticles demonstrated slowed drug dissolution, were non-toxic to human airway epithelial cells, and effectively inhibited the growth of *Pseudomonas aeruginosa* and *Staphylococcus aureus*.
• Particle size and neutral charge suggest potential for mucus penetration and bacterial targeting.

Conclusions:

• LVX-ECM nanoparticles represent a promising, non-toxic inhaled therapy for cystic fibrosis lung infections.
• This hybrid formulation may offer an improved treatment option by addressing both bacterial burden and potentially aiding lung repair.
• Further development of LVX-ECM nanoparticles could advance care for pulmonary bacterial infections in CF patients.