Engineering heparin-azithromycin microparticulate nasal gels for the dual prophylaxis and therapy of COVID-19 and bacterial respiratory infections

The SARS-CoV-2 pandemic highlighted the need for effective prophylactic and local treatment strategies against respiratory viruses. The nasal cavity is a critical site for pathogen entry and colonization, and is therefore a critical target for targeted interventions. SARS-CoV-2, as a plethora of other virus, primarily spreads via respiratory droplets infecting nasal epithelial cells. Concurrently, bacteria such as Streptococcus pneumoniae and Pseudomonas aeruginosa, frequently colonize the nasal cavity, causing co-infections and serving as reservoirs for further respiratory tract involvement. This study presents a nasal gel that combines heparin and azithromycin (AZM) microparticles to combat both viral and bacterial infections in the nasal cavity. The formulation exhibits a favorable safety profile with minimal haemolytic toxicity (HC50 > 82 × 10⁷ μg/mL), potent activity against P. aeruginosa and S. pneumoniae at low concentrations (MIC of 15.6 µg/mL and 7.8 µg/mL, respectively), and effective antiviral properties (IC50 of 0.062 µg/mL for Pseudovirus inhibition). These multifaceted properties position the formulation as a promising candidate for a convenient, dual-action therapy in respiratory infection management, offering potentially both treatment and prophylaxis.