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

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:653

Enthalten in:

International journal of pharmaceutics - 653(2024) vom: 25. März, Seite 123841

Sprache:

Englisch

Beteiligte Personen:

Dallal Bashi, Yahya H [VerfasserIn]
Ali, Ahlam [VerfasserIn]
Al Ayoub, Yuosef [VerfasserIn]
Assi, Khaled H [VerfasserIn]
Mairs, Rachel [VerfasserIn]
McCarthy, Helen O [VerfasserIn]
Tunney, Michael M [VerfasserIn]
Kett, Vicky L [VerfasserIn]

Links:

Volltext

Themen:

059QF0KO0R
83905-01-5
Anti-Bacterial Agents
Azithromycin
Cystic fibrosis
Dry powder inhaler
Journal Article
Liposome
Liposomes
Powders
Respiratory infection
Spray drying
Water

Anmerkungen:

Date Completed 08.04.2024

Date Revised 08.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ijpharm.2024.123841

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367573687