Gemifloxacin Mesylate

Gemifloxacin mesylate inhibits bacterial DNA synthesis by targeting DNA gyrase and topoisomerase IV, enzymes essential for bacterial DNA replication. Beyond its antibacterial action, gemifloxacin demonstrates anti-metastatic activity in human breast adenocarcinoma cells. The drug inhibited the migration and invasion of MDA-MB-231 and MDA-MB-453 cells in Transwell and scratch wound-healing assays. Gemifloxacin induced mesenchymal-epithelial transition, characterized by increased E-cadherin expression and decreased vimentin expression.
The mechanism involved suppression of NF-κB activation, as gemifloxacin inhibited IκB phosphorylation and reduced NF-κB/Snail translocation into the nucleus. Gemifloxacin also upregulated Raf kinase inhibitor protein, an endogenous inhibitor of IκB kinase. Knockdown of RKIP by shRNA transfection significantly decreased the inhibitory effect of gemifloxacin on the NF-κB/Snail pathway and reversed the suppression of cell migration and invasion. In an animal model, gemifloxacin effectively inhibited lipopolysaccharide-mediated lung metastasis.

Fig. 1 Gemifloxacin inhibits inducible NF-κB translocation and DNA binding activity in MDA-MB-231 and MDA-MB-453 cells. (Chen T C.; et al. 2014)

Gemifloxacin mesylate nanoparticles were prepared by ionic gelation technique using chitosan and sodium tripolyphosphate, optimized by 32 factorial design. The optimized formulation GF4 containing 0.15% drug, 0.15% chitosan and 0.20% STPP achieved 71 nm particle size, polydispersity index of 0.283, zeta potential of +28.9 mV and entrapment efficiency of 81.11%. The nanoparticles showed biphasic release with an initial burst of 15% in 1 hour and cumulative release of 90.53% at 24 hours. The nanoparticles were incorporated into Poloxamer 407-based in situ gel, which transformed from sol to gel at corneal temperature. The nanoparticle-loaded in situ gel demonstrated sustained drug release and efficient antimicrobial activity against gram-positive and gram-negative bacteria.

Fig. 2 Scanning electron microscopy of Gemifloxacin Mesylate nanoparticles. (Kalaria V J.; et al. 2023)