Poly(sebacic acid) microparticles loaded with azithromycin as potential pulmonary drug delivery system: Physicochemical properties, antibacterial behavior, and cytocompatibility studies

Abstract

Recurrent bacterial infections are a common cause of death for patients with cystic fibrosis and chronic obstructive pulmonary disease. Herein, we present the development of the degradable poly(sebacic acid) (PSA) microparticles loaded with different concentrations of azithromycin (AZ) as a potential powder formulation to deliver AZ locally to the lungs. We characterized microparticle size, morphology, zeta potential, encapsulation efficiency, interaction PSA with AZ and degradation profile in phosphate buffered saline (PBS). The antibacterial properties were evaluated using the Kirby-Bauer method against Staphylococcus aureus. Potential cytotoxicity was evaluated in BEAS-2B and A549 lung epithelial cells by the resazurin reduction assay and live/dead staining. The results show that microparticles are spherical and their size, being in the range of 1–5 μm, should be optimal for pulmonary delivery. The AZ encapsulation efficiency is nearly 100 % for all types of microparticles. The microparticles degradation rate is relatively fast – after 24 h their mass decreased by around 50 %. The antibacterial test showed that released AZ was able to successfully inhibit bacteria growth. The cytotoxicity test showed that the safe concentration of both unloaded and AZ-loaded microparticles was equal to 50 μg/ml. Thus, appropriate physicochemical properties, controlled degradation and drug release, cytocompatibility, and antibacterial behavior showed that our microparticles may be promising for the local treatment of lung infections.