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Titel: Spray-drying of inhalable, multifunctional formulations for the treatment of biofilms formed in cystic fibrosis
VerfasserIn: Lababidi, Nashrawan
Ofosu Kissi, Eric
Elgaher, Walid A. M.
Sigal, Valentin
Haupenthal, Jörg
Schwarz, Bianca C.
Hirsch, Anna K. H.
Rades, Thomas
Schneider, Marc
Sprache: Englisch
Titel: Journal of Controlled Release (JCR)
Bandnummer: 314
Seiten: 62-71
Verlag/Plattform: Elsevier
Erscheinungsjahr: 2019
DDC-Sachgruppe: 500 Naturwissenschaften
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Cystic fibrosis (CF) is a serious lung disease, commonly susceptible to Pseudomonas aeruginosa colonization. The dense mucus together with biofilm formation limit drug permeability and prevent the drug from reaching the site of action, causing treatment failure of the bacterial infection. Besides the use of antibiotics, the mucolytic agent N-acetylcysteine (NAC) is recommended to be co-administered in the treatment of CF. Although several formulations have been developed for inhalation therapy to improve the pulmonary condition in CF patients, there is still no comprehensive study on a combined multifunctional dry powder formulation of antibiotics with NAC. In this work, we developed an innovative multifunctional dry powder inhaler (DPI) formulation based on salt formation between NAC and antibiotics and characterized their solid state properties and physical stability. NAC could be spray dried together with three different antibiotics, azithromycin (Azi), tobramycin (Tobra) and ciprofloxacin (Cipro), without the use of organic solvents to form Azi/NAC, Tobra/NAC and Cipro/NAC DPI formulations. Solid-state characterization of these DPI formulations showed that they were amorphous after spray drying. Azi/NAC and Tobra/NAC form co-amorphous salt systems that were physically stable under storage at stress conditions. For particle characterization, the obtained mass median aerodynamic diameters were in a suitable range for inhalation (< 5.0 μm). The multifunctional antibiotic/NAC formulations conserved or improved the antibiotic susceptibility and showed promising results regarding the inhibition of P. aeruginosa PA14 biofilm formation.
DOI der Erstveröffentlichung: 10.1016/j.jconrel.2019.10.038
URL der Erstveröffentlichung: https://www.sciencedirect.com/science/article/abs/pii/S0168365919306029
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-390897
hdl:20.500.11880/35248
http://dx.doi.org/10.22028/D291-39089
ISSN: 0168-3659
Datum des Eintrags: 17-Feb-2023
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Pharmazie
Professur: NT - Prof. Dr. Anna Hirsch
NT - Prof. Dr. Marc Schneider
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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