In vivo Efficacy of a Dry Powder Formulation of Ciprofloxacin-Copper Complex in a Chronic Lung Infection Model of Bioluminescent Pseudomonas aeruginosa

Autor: Frederic Tewes, Hugh D. C. Smyth, Tania F. Bahamondez-Canas, Daniel Moraga-Espinoza, Alan B. Watts
Přispěvatelé: Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Molecular Pharmaceutics and Drug Delivery [Austin, TX, USA] (College of Pharmacy), The University of Texas at Austin, Universidad de Valparaiso [Chile], Tewes, Frederic
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
food.ingredient
Chemistry
Pharmaceutical
Pharmaceutical Science
02 engineering and technology
medicine.disease_cause
030226 pharmacology & pharmacy
Permeability
Microbiology
Rats
Sprague-Dawley
03 medical and health sciences
Pulmonary Absorption
0302 clinical medicine
food
Ciprofloxacin
In vivo
Administration
Inhalation
medicine
Animals
Agar
Pseudomonas Infections
Lung
Respiratory Tract Infections
[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Inhalation exposure
Chemistry
Pseudomonas aeruginosa
Dry Powder Inhalers
General Medicine
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
021001 nanoscience & nanotechnology
Antimicrobial
Anti-Bacterial Agents
Rats
3. Good health
[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences
Disease Models
Animal
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Biofilms
Spray drying
Powders
0210 nano-technology
Copper
Biotechnology
medicine.drug
Zdroj: European Journal of Pharmaceutics and Biopharmaceutics
European Journal of Pharmaceutics and Biopharmaceutics, Elsevier, 2020, 152, pp.201-217. ⟨10.1016/j.ejpb.2020.05.014⟩
ISSN: 0939-6411
DOI: 10.1016/j.ejpb.2020.05.014⟩
Popis: International audience; A significant limitation of locally delivered treatments for chronic pulmonary infections is often the short residence time within the airways. Ciprofloxacin (CIP), for example, undergoes rapid absorption from the airway lumen. Previously, we demonstrated that the complexation of CIP with copper (CIP-Cu) reduces its apparent epithelial permeability and pulmonary absorption rate without affecting antimicrobial activity against Pseudomonas aeruginosa grown planktonically or as biofilms. This study aimed to evaluate the in vivo efficacy of CIP-Cu, prepared as a dry powder, in a chronic lung infection model. The powders were prepared by jet milling (CIP-HCl) and by spray drying (CIP-Cu). A bioluminescent strain of P. aeruginosa (PAO1::p16Slux) was used to prepare bacteria-loaded agar beads that were inoculated intratracheally to rats. The dynamics of the infection were monitored using luminometry. The bacteria/beads ratio was optimized to allow the highest luminescence signal and animal survival for 8 days. The efficacy of the treatment was evaluated by luminometry in addition to the end-point (Day 8) where colony counting was performed after lung harvesting. Luminescent P. aeruginosa entrapped in agar beads were useful to monitor the spatial development of the chronic lung infection in rats. The rats were treated with the dry powders in a nose-only inhalation exposure system (NOIES). CIP-Cu and CIP-HCl powders showed similar aerodynamic properties and comparable CIP lung deposition. However, treatment with CIP-Cu significantly (p
Databáze: OpenAIRE
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