Antibiotic‐Loaded Amphiphilic Chitosan Nanoparticles Target Macrophages and Kill an Intracellular Pathogen
In this work, levofloxacin (LVX), a third‐generation fluoroquinolone antibiotic, is encapsulated within amphiphilic polymeric nanoparticles of a chitosan‐g‐poly(methyl methacrylate) produced by self‐assembly and physically stabilized by ionotropic crosslinking with sodium tripolyphosphate. Non‐cross...
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Published in | Small (Weinheim an der Bergstrasse, Germany) Vol. 18; no. 28; pp. e2201853 - n/a |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
Wiley Subscription Services, Inc
01.07.2022
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Subjects | |
Online Access | Get full text |
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Summary: | In this work, levofloxacin (LVX), a third‐generation fluoroquinolone antibiotic, is encapsulated within amphiphilic polymeric nanoparticles of a chitosan‐g‐poly(methyl methacrylate) produced by self‐assembly and physically stabilized by ionotropic crosslinking with sodium tripolyphosphate. Non‐crosslinked nanoparticles display a size of 29 nm and a zeta‐potential of +36 mV, while the crosslinked counterparts display 45 nm and +24 mV, respectively. The cell compatibility, uptake, and intracellular trafficking are characterized in the murine alveolar macrophage cell line MH‐S and the human bronchial epithelial cell line BEAS‐2B in vitro. Internalization events are detected after 10 min and the uptake is inhibited by several endocytosis inhibitors, indicating the involvement of complex endocytic pathways. In addition, the nanoparticles are detected in the lysosomal compartment. Then, the antibacterial efficacy of LVX‐loaded nanoformulations (50% w/w drug content) is assessed in MH‐S and BEAS‐2B cells infected with Staphylococcus aureus and the bacterial burden is decreased by 49% and 46%, respectively. In contrast, free LVX leads to a decrease of 8% and 5%, respectively, in the same infected cell lines. Finally, intravenous injection to a zebrafish larval model shows that the nanoparticles accumulate in macrophages and endothelium and demonstrate the promise of these amphiphilic nanoparticles to target intracellular infections.
Levofloxacin‐loaded chitosan‐g‐poly(methyl methacrylate) nanoparticles are produced and their interaction with cells that serve as host to intracellular infections is investigated. The antibacterial efficacy of the nanoparticles is confirmed in alveolar macrophages and bronchial epithelial cells infected with Staphylococcus aureus and upon intravenous injection to a zebrafish larvae the nanoparticles are accumulated in macrophages and endothelium. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1613-6810 1613-6829 |
DOI: | 10.1002/smll.202201853 |