A novel inhaled multi-pronged attack against respiratory bacteria

Area of Science:

• Pharmaceutical Sciences
• Respiratory Medicine
• Infectious Diseases

Background:

• Airway mucus hypersecretion complicates severe respiratory diseases, creating environments for difficult-to-treat bacterial infections.
• Thickened mucus promotes bacterial growth and hinders effective eradication, posing significant clinical challenges.
• Current treatments lack direct inhaled dry powder formulations for efficient delivery to mucoid infections.

Purpose of the Study:

• To develop a novel ternary dry powder inhaler (DPI) formulation for respiratory mucoid infections.
• To create a multi-pronged attack strategy involving antibiotic synergy, quorum quenching, and mucociliary clearance.
• To target Pseudomonas aeruginosa, a common pathogen in mucoid respiratory infections.

Main Methods:

• Spray drying was used to prepare the ternary formulation of ciprofloxacin hydrochloride, gatifloxacin hydrochloride, and ambroxol hydrochloride.
• Aerosol performance was evaluated using a multi-stage liquid impinger (MSLI).
• Efficacy was tested in bacteria-spiked artificial sputum medium (ASM).

Main Results:

• Optimized particles exhibited respirable size (d50 ≈ 1.61μm) and suitable morphology.
• The formulation demonstrated high fine particle fractions (∼64-69%) with minimal deposition loss in the inhaler device.
• The ternary formulation with ambroxol showed superior bacterial killing rates compared to antibiotics alone.

Conclusions:

• A novel ternary antibiotic-(non-antibiotic) DPI formulation was successfully developed and optimized.
• The formulation utilizes a unique multi-pronged attack mechanism for enhanced efficacy against mucoid infections.
• This approach offers a promising new therapeutic strategy for challenging respiratory bacterial infections.