Dry powders based on mucus-penetrating nanocomposite microparticles for pulmonary delivery of Antibiotics

Pulmonary antibiotic delivery is increasingly recommended as maintenance therapy for cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection. However, the abnormally thick and sticky mucus present in the respiratory tract of CF patients impairs efficient mucus penetration and limits the range of antibiotics for inhalation treatment. To overcome the obstacles of pulmonary antibiotic delivery, we have developed nanocomposite microparticles (nCmP) for inhalation of antibiotics in the form of dry powder aerosols, which will achieve targeted delivery, rapid mucus penetration, and controlled drug release. Azithromycin and rapamycin loaded nanoparticles were prepared via nanoprecipitation. nCmPs based on mannitol carrier were fabricated by spray drying. Scanning electron microscopy and dynamic light scattering showed 200 nm diameter nanoparticles entrapped in 1 - 2 mu m sized microparticles with smooth morphology. In vitro release testing showed that both drug loaded particles have sustained drug release over 12 hours. Redispersity testing indicated that nanoparticles can be well redispersed after being released from mannitol carriers.