Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis

Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with bio...

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Published in:EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Main Authors: Alhajj, Nasser; Yahya, Mohd Fakharul Zaman Raja; O'Reilly, Niall J.; Cathcart, Helen
Format: Article
Language:English
Published: ELSEVIER 2024
Subjects:
Online Access:https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001129795800001
author Alhajj
Nasser; Yahya
Mohd Fakharul Zaman Raja; O'Reilly
Niall J.; Cathcart
Helen
spellingShingle Alhajj
Nasser; Yahya
Mohd Fakharul Zaman Raja; O'Reilly
Niall J.; Cathcart
Helen
Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis
Pharmacology & Pharmacy
author_facet Alhajj
Nasser; Yahya
Mohd Fakharul Zaman Raja; O'Reilly
Niall J.; Cathcart
Helen
author_sort Alhajj
spelling Alhajj, Nasser; Yahya, Mohd Fakharul Zaman Raja; O'Reilly, Niall J.; Cathcart, Helen
Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
English
Article
Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with biofilm formation hinder antibiotic penetration and prevent them from reaching their target. Mucoactive agents are recommended in the treatment of CF in combination with antibiotics. In spite of the extensive research in developing novel drug combinations for the treatment of lung infection in CF, to our knowledge, there is no study that combines antibiotic, antibiofilm and mucoactive agent in a single inhaled dry powder formulation. In the present study, we investigate the possibility of adding a mucoactive agent to our previously developed ciprofloxacinquercetin (antibiotic-antibiofilm) dry powder for inhalation. Three mucoactive agents, namely mannitol (MAN), N-acetyl-L-cysteine (NAC) and ambroxol hydrochloride (AMB), were investigated for this purpose. The ternary combinations were prepared via spray drying without the addition of excipients. All ternary combinations conserved or improved the antibacterial and biofilm inhibition activities of ciprofloxacin against P. aeruginosa (ATCC 10145). The addition of AMB resulted in an amorphous ternary combination (SD-CQA) with superior physical stability as indicated by DSC and nonambient XRPD. Furthermore, SD-CQA displayed better in vitro aerosolization performance (ED - 71 %; FPF - 49 %) compared to formulations containing MAN and NAC (ED - 64 % and 44 %; FPF - 44 % and 29 %, respectively). In conclusion, a ternary drug combination powder with suitable aerosolization, physical stability and antibacterial/antibiofilm properties was prepared by a single spray drying step.
ELSEVIER
0928-0987
1879-0720
2024
192

10.1016/j.ejps.2023.106654
Pharmacology & Pharmacy
gold
WOS:001129795800001
https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001129795800001
title Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis
title_short Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis
title_full Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis
title_fullStr Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis
title_full_unstemmed Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis
title_sort Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis
container_title EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
language English
format Article
description Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with biofilm formation hinder antibiotic penetration and prevent them from reaching their target. Mucoactive agents are recommended in the treatment of CF in combination with antibiotics. In spite of the extensive research in developing novel drug combinations for the treatment of lung infection in CF, to our knowledge, there is no study that combines antibiotic, antibiofilm and mucoactive agent in a single inhaled dry powder formulation. In the present study, we investigate the possibility of adding a mucoactive agent to our previously developed ciprofloxacinquercetin (antibiotic-antibiofilm) dry powder for inhalation. Three mucoactive agents, namely mannitol (MAN), N-acetyl-L-cysteine (NAC) and ambroxol hydrochloride (AMB), were investigated for this purpose. The ternary combinations were prepared via spray drying without the addition of excipients. All ternary combinations conserved or improved the antibacterial and biofilm inhibition activities of ciprofloxacin against P. aeruginosa (ATCC 10145). The addition of AMB resulted in an amorphous ternary combination (SD-CQA) with superior physical stability as indicated by DSC and nonambient XRPD. Furthermore, SD-CQA displayed better in vitro aerosolization performance (ED - 71 %; FPF - 49 %) compared to formulations containing MAN and NAC (ED - 64 % and 44 %; FPF - 44 % and 29 %, respectively). In conclusion, a ternary drug combination powder with suitable aerosolization, physical stability and antibacterial/antibiofilm properties was prepared by a single spray drying step.
publisher ELSEVIER
issn 0928-0987
1879-0720
publishDate 2024
container_volume 192
container_issue
doi_str_mv 10.1016/j.ejps.2023.106654
topic Pharmacology & Pharmacy
topic_facet Pharmacology & Pharmacy
accesstype gold
id WOS:001129795800001
url https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001129795800001
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