Gatifloxacin

Fluoroquinolones (FQs) are widely prescribed antibiotics that are commonly detected in aquatic environments, but the persistence, fates, and ecotoxicities of new generation FQs have yet to be fully investigated. We investigated the direct and indirect (hydroxyl radical (·OH), singlet oxygen (O21), and excited stated of organic matter (³CDOM^*)) photodegradation of three 3rd generation FQs, moxifloxacin (MOX), gatifloxacin (GAT), and sparfloxacin (SPAR). The photodegradation rates and photolytic quantum yields (Φ_FQ) of the FQs depended on their dissociation species at different pH in a range of 1×10^-4 to 1×10^-3 M mol-photon^-1. Unlike MOX and GAT whose zwitterions had the highest Φ_FQ, the anionic form of SPAR had the highest Φ_FQ. The k_·OH,FQ values were in the order of: k_·OH,SPAR > k_·OH,GAT ≈ k_·OH,MOX with the 10¹⁰M^-1s^-1 order of magnitude. The k_O21,FQ values were in the order of: k_O21,SPAR (∼10⁸M^-1s^-1) > k_O21,MOX (∼10⁷M^-1s^-1) > >> k_O21,GAT (insignificant). Higher k_LC*3,FQ values were observed for MOX (10⁹ to 10¹⁰M^-1s^-1) compared to GAT and SPAR (10⁸ to 10⁹M^-1s^-1). The zwitterions had the highest reactivities with ·OH and the lowest reactivities with O21 and ³CDOM^*. Reactions with ·OH enhanced the formation of transformation products (TPs) from decarboxylation and sidechain oxidation pathways, whereas reactions with O21 and ³CDOM^* enhanced the formation of TPs from sidechain oxidation pathways. Some of the TPs were predicted to exhibit aquatic ecotoxicity and environmental persistence. The half-lives of the FQs were estimated to be 0.42 to 0.67 h for MOX and SPAR, and 4.6 to 4.9 h for GAT. Their half-lives and main photochemical fates depended on the surface water pH and water column depth. These results highlight the key roles that photodegradation plays in removing new generation FQs from aquatic environments, though this might lead to the formation of TPs that are harmful to aquatic ecosystems.

To prolong the ocular residence time of gatifloxacin and enhance its efficacy against bacterial keratitis, this study developed a velocity-controlled polyethylene glycol-dithiothreitol-boric acid (PDB) hydrogel loaded with gatifloxacin.

First, the basic properties of the synthesized PDB hydrogel and the gatifloxacin-loaded PDB hydrogel were assessed. Secondly, the in vitro degradation rate of the drug-loaded PDB was measured in a simulated body fluid environment with pH 7.4/5.5. The release behavior of the drug-loaded PDB was studied using a dialysis method with PBS solution of pH 7.4/5.5 as the release medium. Finally, a mouse model of bacterial keratitis was established, and tissue morphology was observed using hematoxylin-eosin staining. Additionally, mouse tear fluid was extracted to observe the antibacterial effect of the gatifloxacin-loaded PDB hydrogel.

The results showed that the PDB hydrogel had a particle size of 124.9 nm and a zeta potential of -23.3 mV, with good porosity, thermosensitivity, viscosity distribution, rheological properties, and high cell compatibility. The encapsulation of gatifloxacin did not alter the physical properties of the PDB hydrogel and maintained appropriate swelling and stability, with a high drug release rate in acidic conditions. Furthermore, animal experiments demonstrated that the gatifloxacin- loaded PDB hydrogel exhibited superior therapeutic effects compared to gatifloxacin eye drops and displayed strong antibacterial capabilities against bacterial keratitis.

This study successfully synthesized PDB hydrogel and developed a gatifloxacin drug release system. The hydrogel exhibited good thermosensitivity, pH responsiveness, stability, and excellent biocompatibility, which can enhance drug retention, utilization, and therapeutic effects on the ocular surface.