Research Article

The AAPS Journal

, Volume 10, Issue 2, pp 254-260

First online:

Microparticles for Inhalational Delivery of Antipseudomonal Antibiotics

  • Michael D. TsifanskyAffiliated withDepartment of Pediatrics, Division of Pediatric Intensive Care Medicine, Lutheran General Children’s Hospital
  • , Yoon YeoAffiliated withIndustrial and Physical Pharmacy and Biomedical Engineering, Purdue University
  • , Oleg V. EvgenovAffiliated withDepartment of Anesthesia and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School
  • , Evangelia BellasAffiliated withDepartment of Chemical Engineering, Massachusetts Institute of Technology
  • , John BenjaminAffiliated withShriners Hospital for Children-Boston
  • , Daniel S. KohaneAffiliated withLaboratory for Biomaterials and Drug Delivery, Dept of Anesthesiology, Children’s Hospital, Harvard Medical School Email author 


Chronic pseudomonal bronchopulmonary infections in cystic fibrosis patients are frequently controlled with inhaled antibiotics. Dry-powder inhalable antibiotics are an attractive alternative to nebulized medications. We produced and evaluated microparticles composed of dipalmitoylphosphatidylcholine, albumin, and lactose as a model system for intrapulmonary delivery of ceftazidime, ciprofloxacin, and several combinations of the two, none of which is presently available for inhalation. Microparticles containing one or both antibiotics were prepared by spray-drying. Their Anderson cascade impactor deposition profiles showed 10–30% fine particle fractions of the nominal dose. Microparticles containing varying amounts of each antibiotic showed statistically different deposition profiles. Aerodynamics and deposition of microparticles co-encapsulating both antibiotics were similar to those of single-drug microparticles with the same proportion of ciprofloxacin alone. The antipseudomonal activities of microparticles co-encapsulating half of the 50% effective concentration (EC50) of both ceftazidime and ciprofloxacin (5 mg of particles containing 5% ceftazidime and 10% ciprofloxacin) were at least additive compared to particles containing the EC50 of each antibiotic separately (5 mg of particles containing 10% ceftazidime or 5 mg of particles containing 20% ciprofloxacin). Co-encapsulation of the antibiotics in microparticles ensures co-deposition at desired ratios, improves the particles’ aerodynamics and fine particle fraction, as compared to microparticles with equivalent amounts of ceftazidime alone, and achieves additive antipseudomonal activity.


co-encapsulation cystic fibrosis dry-powder inhalational delivery of antibiotics microparticles