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Inhaled dry powder liposomal azithromycin for treatment of chronic lower respiratory tract infection

Dallal Bashi, Y.H.
; 
Ali, A.
; 
Al Ayoub, Y.
; 
Assi, Khaled H.
; 
Mairs, R.
; 
McCarthy, H.O.
; 
Tunney, M.M.
; 
Kett, V.L.
Publication Date
2024-03-25
End of Embargo
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Keywords
Liposome, Azithromycin, Spray drying, Dry powder inhaler, Respiratory infection, Cystic fibrosis
Rights
(c) 2024 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/)
cb
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Yes
Open Access status
openAccess
Accepted for publication
2024-01-20
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Life Sciences Publications
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Abstract
A dry powder inhaled liposomal azithromycin formulation was developed for the treatment of chronic respiratory diseases such as cystic fibrosis and bronchiectasis. Key properties including liposome size, charge and encapsulation efficiency powder size, shape, glass transition temperature (Tg), water content and in vitro respiratory deposition were determined. Antimicrobial activity against cystic fibrosis (CF) respiratory pathogens was determined by MIC, MBC and biofilm assays. Cytotoxicity and cellular uptake studies were performed using A549 cells. The average liposome size was 105 nm, charge was 55 mV and encapsulation efficiency was 75 %. The mean powder particle size d[v,50] of 4.54 µm and Mass Median Aerodynamic Diameter (MMAD) was 5.23 µm with a mean Tg of 76˚C and water content of 2.1 %. These excellent physicochemical characteristics were maintained over one year. Liposomal loaded azithromycin demonstrated enhanced activity against P. aeruginosa clinical isolates grown in biofilm. The formulation was rapidly delivered into bacterial cells with > 75 % uptake in 1 h. Rapid uptake into A549 cells via a cholesterol-dependent endocytosis pathway with no cytotoxic effects apparent. These data demonstrate that this formulation could offer benefits over current treatment regimens for people with chronic respiratory infection.
URI
http://hdl.handle.net/10454/20085
Version
Published version
Citation
Dallal Bashi YH, Ali A, Al Ayoub Y et al (2024) Inhaled dry powder liposomal azithromycin for treatment of chronic lower respiratory tract infection. International Journal of Pharmaceutics. 653: 123841.
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Link to Version of Record
https://doi.org/10.1016/j.ijpharm.2024.123841
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Article
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