A novel inhaled multi-pronged attack against respiratory bacteria
| Autor: | Desmond Heng, Reginald B. H. Tan, Jeanette W. P. Teo, Hak-Kim Chan, Wai Kiong Ng, Yanli Zhao, Li Teng Tan, Sie Huey Lee |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Chemistry
Mucociliary clearance Inhaler Sputum Pharmaceutical Science Dry Powder Inhalers Bacterial Infections Mucus Gatifloxacin Dry-powder inhaler Anti-Bacterial Agents Microbiology Ciprofloxacin X-Ray Diffraction Administration Inhalation Pseudomonas aeruginosa medicine Humans Particle Size medicine.symptom Respiratory Tract Infections Ciprofloxacin Hydrochloride medicine.drug |
| Zdroj: | European Journal of Pharmaceutical Sciences. 70:37-44 |
| ISSN: | 0928-0987 |
| Popis: | Airway mucus hypersecretion is a common clinical feature of many severe respiratory diseases, and when complicated by a recalcitrant bacterial infection, the whole treatment regimen thereby becomes more challenging and protracted. The accumulation of thickened mucus secretions in the lower airways provides a nutrient-rich breeding ground for bacteria that promotes their growth and limits the ease of effective eradication. Unfortunately, no direct-inhaled dry powder formulation to treat these respiratory mucoid infections more effectively is available commercially. This work therefore seeks to develop a highly-efficacious ternary dry powder inhaler (DPI) formulation (ciprofloxacin hydrochloride (CIP), gatifloxacin hydrochloride (GAT) and ambroxol hydrochloride (AMB)) capable of delivering a novel multi-pronged attack (synergy, quorum quenching and mucociliary clearance) on Pseudomonas aeruginosa, a common respiratory bacteria found in mucoid infections. The powders were prepared via spray drying, evaluated on their aerosol performance via a multi-stage liquid impinger (MSLI) and tested for their efficacies in bacteria-spiked artificial sputum medium (ASM). The optimized particles were of respirable-size (d50 of ∼1.61±0.03μm) and slightly corrugated. When dispersed via an Aerolizer® inhaler at 60L/min, the powder showed concomitant in vitro deposition, minimal capsule, device and throat retention, and highly promising and uniform fine particle fractions (of the loaded dose) of ∼64-69%, which was a vast improvement over the singly-delivered actives. Favourably, when tested on bacteria-spiked ASM, the optimized ternary formulation (with AMB) was more effective at killing bacteria (i.e. faster rate of killing) than just the synergistic antibiotics alone (binary formulation; without AMB). In conclusion, a ternary antibiotic-(non-antibiotic) DPI formulation involving a unique multi-pronged attack mechanism was successfully pioneered and optimized for mucoid infections. |
| Databáze: | OpenAIRE |
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