Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals
Uloženo v:
| Název: | Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals |
|---|---|
| Autoři: | Durairaj Thiyagarajan, Benedikt Huck, Birgit Nothdurft, Marcus Koch, David Rudolph, Mark Rutschmann, Claus Feldmann, Constantin Hozsa, Marcus Furch, Karen F. W. Besecke, Robert K. Gieseler, Brigitta Loretz, Claus-Michael Lehr |
| Přispěvatelé: | HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. |
| Zdroj: | Drug Deliv Transl Res Drug delivery and translational research United States Drug Delivery and Translational Research, 11, 1766–1778 |
| Informace o vydavateli: | Springer Science and Business Media LLC, 2021. |
| Rok vydání: | 2021 |
| Témata: | Original Paper, Lactose/chemistry [MeSH], Levofloxacin, Respiratory infections, Lung/metabolism [MeSH], Benzothiazinone, Antibacterial nanoparticles, Powders/chemistry [MeSH], Liposomes, Tuberculosis, Powders/metabolism [MeSH], Dry powder formulations, Leucine/chemistry [MeSH], Particle Size [MeSH], Drug Delivery Systems/methods [MeSH], ddc:540, Chemistry & allied sciences, Lactose, 3. Good health, Drug Delivery Systems, Leucine, Particle Size, Powders, Lung |
| Popis: | Pulmonary delivery of nanocarriers for novel antimycobacterial compounds is challenging because the aerodynamic properties of nanomaterials are sub-optimal for such purposes. Here, we report the development of dry powder formulations for nanocarriers containing benzothiazinone 043 (BTZ) or levofloxacin (LVX), respectively. The intricacy is to generate dry powder aerosols with adequate aerodynamic properties while maintaining both nanostructural integrity and compound activity until reaching the deeper lung compartments. Microparticles (MPs) were prepared using vibrating mesh spray drying with lactose and leucine as approved excipients for oral inhalation drug products. MP morphologies and sizes were measured using various biophysical techniques including determination of geometric and aerodynamic mean sizes, X-ray diffraction, and confocal and focused ion beam scanning electron microscopy. Differences in the nanocarriers’ characteristics influenced the MPs’ sizes and shapes, their aerodynamic properties, and, hence, also the fraction available for lung deposition. Spay-dried powders of a BTZ nanosuspension, BTZ-loaded silica nanoparticles (NPs), and LVX-loaded liposomes showed promising respirable fractions, in contrast to zirconyl hydrogen phosphate nanocontainers. While the colloidal stability of silica NPs was improved after spray drying, MPs encapsulating either BTZ nanosuspensions or LVX-loaded liposomes showed the highest respirable fractions and active pharmaceutical ingredient loads. Importantly, for the BTZ nanosuspension, biocompatibility and in vitro uptake by a macrophage model cell line were improved even further after spray drying. Graphical abstract |
| Druh dokumentu: | Article Other literature type |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 2190-3948 2190-393X |
| DOI: | 10.1007/s13346-021-01011-7 |
| DOI: | 10.22028/d291-34431 |
| DOI: | 10.5445/ir/1000134294 |
| DOI: | 10.34657/7254 |
| Přístupová URL adresa: | https://link.springer.com/content/pdf/10.1007/s13346-021-01011-7.pdf https://pubmed.ncbi.nlm.nih.gov/34101127 https://link.springer.com/content/pdf/10.1007/s13346-021-01011-7.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236044/ https://europepmc.org/article/MED/34101127 https://pubmed.ncbi.nlm.nih.gov/34101127/ https://link.springer.com/article/10.1007/s13346-021-01011-7 http://hdl.handle.net/10033/622919 https://publikationen.bibliothek.kit.edu/1000134294 https://doi.org/10.5445/IR/1000134294 https://publikationen.bibliothek.kit.edu/1000134294/118887797 https://repository.publisso.de/resource/frl:6444106 |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . |
| Přístupové číslo: | edsair.doi.dedup.....3ff36ee5997f1039403fb4f353ee22c1 |
| Databáze: | OpenAIRE |
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstrakt: | Pulmonary delivery of nanocarriers for novel antimycobacterial compounds is challenging because the aerodynamic properties of nanomaterials are sub-optimal for such purposes. Here, we report the development of dry powder formulations for nanocarriers containing benzothiazinone 043 (BTZ) or levofloxacin (LVX), respectively. The intricacy is to generate dry powder aerosols with adequate aerodynamic properties while maintaining both nanostructural integrity and compound activity until reaching the deeper lung compartments. Microparticles (MPs) were prepared using vibrating mesh spray drying with lactose and leucine as approved excipients for oral inhalation drug products. MP morphologies and sizes were measured using various biophysical techniques including determination of geometric and aerodynamic mean sizes, X-ray diffraction, and confocal and focused ion beam scanning electron microscopy. Differences in the nanocarriers’ characteristics influenced the MPs’ sizes and shapes, their aerodynamic properties, and, hence, also the fraction available for lung deposition. Spay-dried powders of a BTZ nanosuspension, BTZ-loaded silica nanoparticles (NPs), and LVX-loaded liposomes showed promising respirable fractions, in contrast to zirconyl hydrogen phosphate nanocontainers. While the colloidal stability of silica NPs was improved after spray drying, MPs encapsulating either BTZ nanosuspensions or LVX-loaded liposomes showed the highest respirable fractions and active pharmaceutical ingredient loads. Importantly, for the BTZ nanosuspension, biocompatibility and in vitro uptake by a macrophage model cell line were improved even further after spray drying. Graphical abstract |
|---|---|
| ISSN: | 21903948 2190393X |
| DOI: | 10.1007/s13346-021-01011-7 |