Novel copolymers of poly(sebacic anhydride) and poly(ethylene glycol) as azithromycin carriers to the lungs

• Autorzy: Kwiecień Konrad , Knap Karolina , Heida Rick , Czajkowski Jonasz , Gorter Alan , Ochońska Dorota , Mielczarek Przemysław , Dorosz Agata , Niewolik Daria , Reczyńska-Kolman Katarzyna , Jaszcz Katarzyna , Brzychczy-Włoch Monika , Sosnowski Tomasz R. , Olinga Peter , Pamuła Elżbieta

Identyfikatory

DOI

10.1016/j.bbe.2025.01.002

• Języki publikacji: EN

Abstrakty

EN

By many chronic lung diseases, there is a problem of recurrent bacterial infections that require frequent usage of antibiotics. They can be more effective and cause fewer side effects when administrated directly via the pulmonary route. For such purposes, various types of inhalers are used of which dry powder inhalers (DPIs) are one of the most common. Formulations such as dry powders usually consist of an active pharmaceutical ingredient (API) and a carrier material that is supposed to provide adequate properties to deliver the bioactive molecules to the site of action, effectively. Copolymers of sebacic acid (SA) and poly(ethylene glycol) (PEG) have been regarded as suitable materials for such formulations. Here, we present a study about the manufacturing of microparticles from such materials dedicated to inhalation which have been loaded with azithromycin (AZM). The microparticles (MPs) were 0.5 to 5 μm in size, presenting either a spherical or elongated shape depending on the material type and composition. The encapsulation efficiency (EE) of the MPs were almost complete with the drug loading up to 23.1 %. The powders had fair or good flowability based on Carr’s index and Hausner ratio. Due to the presence of the drug, the tendency to agglomerate decreased. As a result, up to 90 % of the obtained powders showed diameters below 5 μm. Also, the fine particles fraction (FPF) of the chosen formulation reached 66.3 ± 4.5 % and the mass median aerodynamic diameter was 3.8 ± 0.4 μm. The microparticles degraded quickly in vitro losing up to 50 % of their mass within 24 h and up to 80 % within 96 h of their incubation in phosphate-buffered saline (PBS). They were also nontoxic up to 100 μg/ml when added to cultures of A549 and BEAS-2B lung epithelial cells as well as to rat lung tissue slices tested ex vivo. The microparticles showed bactericidal effects against various strains of Staphylococcus aureus in lower than cytotoxic concentrations.

Słowa kluczowe

EN

azithromycin; dry powder for inhalation; pulmonary drug delivery; polyanhydrides

PL

azytromycyna; dopłucne dostarczanie leków; polianhydrydy

• Wydawca: Nałęcz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences ; Elsevier
• Czasopismo: Biocybernetics and Biomedical Engineering
• Rocznik: 2025
• Tom: Vol. 45, iss. 1
• Strony: 114--136
• Opis fizyczny: Bibliogr. 73 poz., rys., tab., wykr.

Twórcy

autor

Kwiecień Konrad

• Department of Biomaterials and Composites, Faculty of Materials Science and Ceramics, AGH University of Krakow, Al. Mickiewicza 30, 30-059 Kraków, Poland

• https://orcid.org/0000-0002-9504-1205

autor

Knap Karolina

• Department of Biomaterials and Composites, Faculty of Materials Science and Ceramics, AGH University of Krakow, Al. Mickiewicza 30, 30-059 Kraków, Poland

• https://orcid.org/0000-0002-6018-293X

autor

Heida Rick

• Department of Pharmaceutical Technology and Biopharmacy, Faculty of Science and Engineering, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, Netherlands

• https://orcid.org/0000-0002-8425-394X

autor

Czajkowski Jonasz

• Faculty of Electrical Engineering, Automatics, Computer Science, and Biomedical Engineering, AGH University of Krakow, Al. Mickiewicza 30, 30-059 Kraków, Poland

• https://orcid.org/0009-0007-3141-1696

autor

Gorter Alan

• Department of Pharmaceutical Technology and Biopharmacy, Faculty of Science and Engineering, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, Netherlands

autor

Ochońska Dorota

• Department of Molecular Medical Microbiology, Chair of Microbiology, Faculty of Medicine, Jagiellonian University Medical College, 18 Czysta Street, 31-121 Kraków, Poland

autor

Mielczarek Przemysław

• Department of Analytical Chemistry and Biochemistry, Faculty of Materials Science and Ceramics, AGH University of Krakow, Al. Mickiewicza 30, 30-059 Kraków, Poland

autor

Dorosz Agata

• Chair of Dispersed Systems Engineering, Faculty of Chemical and Process Engineering Warsaw University of Technology, ul. Waryńskiego 1, 00-645 Warsaw, Poland

• https://orcid.org/0000-0002-8487-0390

autor

Niewolik Daria

• Silesian University of Technology, Faculty of Chemistry, Department of Physical Chemistry and Technology of Polymers, ul. M. Strzody 9, 44-100 Gliwice, Poland

autor

Reczyńska-Kolman Katarzyna

• Department of Biomaterials and Composites, Faculty of Materials Science and Ceramics, AGH University of Krakow, Al. Mickiewicza 30, 30-059 Kraków, Poland

autor

Jaszcz Katarzyna

• Silesian University of Technology, Faculty of Chemistry, Department of Physical Chemistry and Technology of Polymers, ul. M. Strzody 9, 44-100 Gliwice, Poland

autor

Brzychczy-Włoch Monika

• Department of Molecular Medical Microbiology, Chair of Microbiology, Faculty of Medicine, Jagiellonian University Medical College, 18 Czysta Street, 31-121 Kraków, Poland

autor

Sosnowski Tomasz R.

• Chair of Dispersed Systems Engineering, Faculty of Chemical and Process Engineering Warsaw University of Technology, ul. Waryńskiego 1, 00-645 Warsaw, Poland

autor

Olinga Peter

• Department of Pharmaceutical Technology and Biopharmacy, Faculty of Science and Engineering, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, Netherlands

autor

Pamuła Elżbieta

• Department of Biomaterials and Composites, Faculty of Materials Science and Ceramics, AGH University of Krakow, Al. Mickiewicza 30, 30-059 Kraków, Poland

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Uwagi

Opracowanie rekordu ze środków MNiSW, umowa nr POPUL/SP/0154/2024/02 w ramach programu "Społeczna odpowiedzialność nauki II" - moduł: Popularyzacja nauki (2025).