Antibiotic-loaded amphiphilic chitosan nanoparticles target macrophages and kill an intracellular pathogen

0559145 - ÚMCH 2023 RIV DE eng J - Journal Article
Trousil, Jiří - Dal, N.-J. K. - Fenaroli, F. - Schlachet, I. - Kubíčková, P. - Janoušková, Olga - Pavlova, Ewa - Škorič, M. - Trejbalová, Kateřina - Pavliš, O. - Sosnik, A.
Antibiotic-loaded amphiphilic chitosan nanoparticles target macrophages and kill an intracellular pathogen.
Small. Roč. 18, č. 28 (2022), č. článku 2201853. ISSN 1613-6810. E-ISSN 1613-6829
Grant - others:AV ČR(CZ) MSM200502101
Program: Program na podporu mezinárodní spolupráce začínajících výzkumných pracovníků
Institutional support: RVO:61389013 ; RVO:68378050
Keywords : amphiphilic chitosan nanoparticles * intracellular infections * levofloxacin
OECD category: Biomaterials (as related to medical implants, devices, sensors); Virology (UMG-J)
Impact factor: 13.3, year: 2022
Method of publishing: Limited access
https://onlinelibrary.wiley.com/doi/10.1002/smll.202201853

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.

Permanent Link: https://hdl.handle.net/11104/0333075