Inhaled dry powder liposomal azithromycin for treatment of chronic lower respiratory tract infection.
Int J Pharm
; 653: 123841, 2024 Mar 25.
Article
em En
| MEDLINE
| ID: mdl-38266939
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 76ËC 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.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Infecções Respiratórias
/
Fibrose Cística
Limite:
Humans
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido