Fumaryl diketopiperazine based effervescent microparticles to escape macrophage phagocytosis for enhanced treatment of pneumonia via pulmonary delivery.

The treatment of pulmonary infections with antibiotics administered via pulmonary delivery provides for higher local therapeutic efficacy rather than through systemic administration. Pneumonia is globally considered a major cause of death due to a lack of proper medication. The treatment of pneumonia with inhalable antibiotics (such as azithromycin (AZM)) can provide a maximum pulmonary therapeutic effect without significant systemic side effects. Compared to non-effervescent microparticles, effervescent microparticles can provide an active driving force to release loaded antibiotics for subsequent distribution deep into the lung by virtue of its smaller size. In this study, N-fumaroylated diketopiperazine (FDKP) was used as a carrier to prepare effervescent inhalable microparticles loaded with AZM (AZM@FDKP-E-MPs). This effervescent dry powder was characterized for both in vitro and in vivo deposition in the lung and the results obtained showed significant improvement in lung deposition and anti-bacterial efficiency, suggesting a strong potential application for pneumonia treatment.