The AAPS Journal

, 10:254

Microparticles for Inhalational Delivery of Antipseudomonal Antibiotics

Authors

  • Michael D. Tsifansky
    • Department of Pediatrics, Division of Pediatric Intensive Care MedicineLutheran General Children’s Hospital
  • Yoon Yeo
    • Industrial and Physical Pharmacy and Biomedical EngineeringPurdue University
  • Oleg V. Evgenov
    • Department of Anesthesia and Critical Care Medicine, Massachusetts General HospitalHarvard Medical School
  • Evangelia Bellas
    • Department of Chemical EngineeringMassachusetts Institute of Technology
  • John Benjamin
    • Shriners Hospital for Children-Boston
    • Laboratory for Biomaterials and Drug Delivery, Dept of Anesthesiology, Children’s HospitalHarvard Medical School
Research Article

DOI: 10.1208/s12248-008-9033-8

Cite this article as:
Tsifansky, M.D., Yeo, Y., Evgenov, O.V. et al. AAPS J (2008) 10: 254. doi:10.1208/s12248-008-9033-8

Abstract

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.

KEY WORDS

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

Copyright information

© American Association of Pharmaceutical Scientists 2008