Integration of 3D-printed micromixers and spray drying for pulmonary delivery of antimicrobial microparticles

Abstract

Pulmonary drug delivery is crucial for treating respiratory diseases, requiring precise particle engineering for optimal therapeutic efficacy. This study demonstrates a novel integration of 3D-printed microfluidic micromixers with spray drying technology to produce inhalable azithromycin (AZM) microparticles targeting lung delivery. The formulation demonstrated effective deep lung deposition at both 30 L/min and 60 L/min flow rates. At 30 L/min, AZM-loaded microparticles achieved enhanced performance with 1.2-fold higher Fine Particle Fraction (FPF) < 5 µm and 1.4-fold higher FPF < 3 µm compared to 60 L/min. Microparticles (25 mg) can deliver an efficacious dose of AZM to the lung, exceeding the reported epidemiological cut-off for Haemophilus influenzae (4 mg/L) by approximately five-fold while maintaining high human bronchial epithelial cell viability (> 94 %). The antibacterial efficacy against H. influenzae was confirmed, demonstrating the therapeutic potential against lung pathogens. The successful deep lung deposition at both air flow rates reflects the robustness of the formulation design, making it suitable for diverse patient populations with varying inspiratory capabilities, including children and elderly patients.