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.
摘要：
在这项工作中,左氧氟沙星（LVX），第三代氟喹诺酮类抗生素,被封装在壳聚糖-g-聚（甲基丙烯酸甲酯）的两亲性聚合物纳米颗粒中，该壳聚糖-g-聚（甲基丙烯酸甲酯）通过自组装产生并通过与三聚磷酸钠的离子交联而物理稳定。非交联纳米颗粒的尺寸为29nm，ζ电位为+36mV，而交联对应物显示45nm和+24mV，分别。细胞的兼容性，摄取，和细胞内运输的特征在于体外在鼠肺泡巨噬细胞系MH-S和人支气管上皮细胞系BEAS-2B中。10分钟后检测到内化事件，摄取被几种内吞抑制剂抑制，表明复杂的内吞途径的参与。此外,在溶酶体区室中检测到纳米颗粒。然后，在感染金黄色葡萄球菌的MH-S和BEAS-2B细胞中评估了负载LVX的纳米制剂（50％w/w药物含量）的抗菌功效，细菌负荷降低了49％和46％，分别。相比之下,游离LVX导致8%和5%的下降，分别,在相同的感染细胞系中。最后,静脉注射斑马鱼幼虫模型表明，纳米颗粒在巨噬细胞和内皮中积累，并证明这些两亲性纳米颗粒有望靶向细胞内感染。
