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Microparticles for inhalational delivery of antipseudomonal antibiotics
Michael D Tsifansky1, Yoon Yeo, Oleg V Evgenov
1Department of Pediatrics, Division of Pediatric Intensive Care Medicine, Lutheran General Children's Hospital, 1775 Dempster St., Park Ridge, Illinois, 60068, USA.
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 (EC(50)) of both ceftazidime and ciprofloxacin (5 mg of particles containing 5% ceftazidime and 10% ciprofloxacin) were at least additive compared to particles containing the EC(50) 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.
Insights
New dry-powder inhalable antibiotics offer a promising alternative for cystic fibrosis patients with chronic pseudomonal infections. These microparticles improve drug delivery and show additive antibacterial activity.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Infectious Diseases
Background:
- Chronic *Pseudomonas* aeruginosa infections are a major cause of morbidity and mortality in cystic fibrosis (CF) patients.
- Inhaled antibiotics are a cornerstone of CF treatment, but nebulized formulations have limitations.
- Dry-powder inhalable antibiotics represent an attractive alternative for improved pulmonary drug delivery.
Purpose of the Study:
- To develop and characterize microparticles for intrapulmonary delivery of ceftazidime and ciprofloxacin, alone or in combination.
- To evaluate the aerodynamic properties and deposition of these novel antibiotic-loaded microparticles.
- To assess the in vitro antipseudomonal activity of co-encapsulated antibiotics.
Main Methods:
- Microparticles were formulated using spray-drying with dipalmitoylphosphatidylcholine, albumin, and lactose.
- Antibiotic-loaded microparticles (ceftazidime, ciprofloxacin, or both) were characterized for aerodynamic performance using an Anderson cascade impactor.
- Antipseudomonal activity was determined by comparing the efficacy of co-encapsulated antibiotics versus single-drug formulations.
Main Results:
- Spray-dried microparticles achieved fine particle fractions of 10-30% of the nominal dose.
- Co-encapsulation of ceftazidime and ciprofloxacin resulted in similar aerodynamic profiles compared to single-drug microparticles.
- Combined antibiotic microparticles demonstrated at least additive antipseudomonal activity compared to individual antibiotic formulations.
Conclusions:
- Co-encapsulation of ceftazidime and ciprofloxacin in microparticles ensures desired drug ratios and improves aerodynamic properties.
- This novel dry-powder formulation enhances fine particle fraction and achieves additive antimicrobial efficacy.
- These findings support the potential of inhaled antibiotic microparticles as an improved therapeutic strategy for CF lung infections.
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