Heparin-azithromycin microparticles show anti-inflammatory effects and inhibit SARS-CoV-2 and bacterial pathogens...

Area of Science:

• Pulmonary Medicine
• Infectious Diseases
• Nanotechnology

Background:

• Pulmonary infections pose significant global health risks, worsened by COVID-19.
• Azithromycin (AZM) is an oral antibiotic that concentrates in lung tissues.
• Sulfated polysaccharides, like heparin, inhibit SARS-CoV-2 viral entry.

Purpose of the Study:

• To develop and evaluate a novel dry powder inhaler (DPI) formulation of azithromycin-loaded microparticles.
• To incorporate heparin or its derivatives into microparticles for enhanced pulmonary drug delivery.
• To assess the antiviral and antibacterial efficacy and safety of the novel DPI formulation.

Main Methods:

• Development of azithromycin-loaded microparticles using heparin or its derivatives.
• In vitro testing for antiviral activity against SARS-CoV-2.
• In vitro testing for antibacterial efficacy against Streptococcus pneumoniae and Pseudomonas aeruginosa.
• Cytotoxicity assays on mammalian cells (Calu-3, red blood cells).
• Aerodynamic characterization of microparticle formulations (MMAD, FPF).

Main Results:

• Microparticle formulations demonstrated potent antiviral activity against SARS-CoV-2 (IC50 ≤ 95 nM).
• Superior antibacterial efficacy against S. pneumoniae and P. aeruginosa compared to free AZM (MIC ≤ 15 μg/mL).
• No observed cytotoxicity on mammalian cells at bactericidal concentrations.
• Effective alveolar aerodynamic deposition with MMAD of 1-3 μm and FPF near 50%.

Conclusions:

• The novel DPI formulation delivers effective local concentrations of AZM and sulfated polysaccharides to the lungs.
• This multifaceted strategy shows promise for treating bacterial pulmonary infections, including those associated with COVID-19.
• The formulation offers a potentially improved therapeutic option for pulmonary infections.