Antibiotic‐Loaded Amphiphilic Chitosan Nanoparticles Target Macrophages and Kill an Intracellular Pathogen

Abstract

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.

Regulating the microenvironment with nanomaterials: Potential strategies to ameliorate COVID-19

“…8 ). Polymer NPs that are degraded have also been introduced to regulate macrophages 180 , 181 , 182 , 183 . For example, Kraynak et al 184 developed NPs composed of a PLGA core and phosphatidylserine (PS)-supplemented cell plasma membrane (PS-MNPs).…”

Rifampicin-Loaded Polyelectrolyte Complex Eliminates Intracellular Bacteria through Thiol-Mediated Cellular Uptake and Oxidative Stress Enhancement

“…17−23 For example, Trousil et al developed levofloxacin-loaded chitosan-g-poly(methyl methacrylate) nanoparticles against intracellular bacterial infection. 24 The S. aureus in macrophages and epithelial cells were reduced by 49 and 46%, respectively. However, it is still far from the eradication requirement of more than 90% because of the endocytosis-dependent cell uptake, which allows most antibiotics to be trapped and subsequently degraded in the endosome.…”

“…Nanoparticles are widely used for intracellular delivery of antibiotics due to their high cellular uptake efficiency and targeting ability. − For example, Trousil et al developed levofloxacin-loaded chitosan- g -poly­(methyl methacrylate) nanoparticles against intracellular bacterial infection . The S.…”

Affinity of cefotiam for the alternative penicillin binding protein PBP3SAL used by Salmonella inside host eukaryotic cells

“…To counterbalance these negative effects, new approaches based on highly penetrating nanoparticles carrying the drug as cargo are currently under intense investigation and development. 4 …”