Inhalable combination powder formulations of phage and ciprofloxacin for P. aeruginosa respiratory infections

Inhalable combination powder formulations of phage and ciprofloxacin for P. aeruginosa respiratory infections.

Full text not available from this repository.
Item Type: Article
Status: Published
Official URL: https://doi.org/10.1016/j.ejpb.2019.08.004
Journal or Publication Title: European Journal of Pharmaceutics and Biopharmaceutics
Volume: 142
Page Range: pp. 543-552
Date: 2019
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1016/j.ejpb.2019.08.004
ISSN: 09396411
Date Deposited: 21 Dec 2020 23:17
Abstract:

Recently we showed that nebulized ciprofloxacin and phage PEV20 in combination had a synergistic bactericidal effect against antibiotic-resistant Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Compared to nebulization, dry powders for inhalation may improve patient handling characteristics and compliance. In the present study, we co-spray dried ciprofloxacin and phage PEV20 using L-leucine with or without lactose as excipients. Two formulations were identified for testing in this study. The mass ratios were set at 1:1:1 for ciprofloxacin, lactose and L-leucine (Formulation A) or 2:1 for ciprofloxacin and L-leucine without lactose (Formulation B). Concentrations of PEV20 were set at 108 and 109 PFU/mL for two clinical P. aeruginosa strains FADD1-PA001 and JIP865, respectively. Formulations A and B were characterized as partially crystalline and the powders recrystallized at >40% relative humidity (RH). Both formulations exhibited strong synergistic antimicrobial killing effect on the two strains. Formulations A and B maintained bactericidal synergy after dispersion using both low and high resistance Osmohaler™. Powder aerosol performance was examined by next generation impactor (NGI) in low resistance inhaler at 100 L/min and by multi-stage liquid impinger (MSLI) in high resistance inhaler at 60 L/min. Fine particle fractions (FPF) obtained by NGI were 59.7 ± 2.1% and 64.3 ± 2.9% for A and B, respectively. FPF obtained by MSLI were 71.0 ± 3.4% and 73.3 ± 5.0%, respectively. In conclusion, it is feasible to prepare stable and inhalable combination powder formulations of phage PEV20 and ciprofloxacin for potential treatment of respiratory infections caused by multi-drug resistant (MDR) P. aeruginosa.

Keywords: Bacteriophages; Ciprofloxacin; Cystic fibrosis; Inhalation; L-leucine; Powder formulation; Pseudomonas aeruginosa; Respiratory infection; Spray drying.

Copyright © 2019 Elsevier B.V. All rights reserved.

Creators:
Creators
Email
Lin, Yu
UNSPECIFIED
Chang, Rachel Yoon Kyung
UNSPECIFIED
Britton, Warwick J.
UNSPECIFIED
Morales, Sandra
UNSPECIFIED
Kutter, Elizabeth
UNSPECIFIED
Li, Jian
UNSPECIFIED
Chan, Hak-Kim
UNSPECIFIED
Last Modified: 21 Dec 2020 23:17
URI: https://eprints.centenary.org.au/id/eprint/149

Actions (login required)

View Item View Item