A methacrylated hyaluronic acid network reinforced Pluronic F-127 gel for treatment of bacterial keratitis

Abstract

In this study, we developed a novel in situ thermoresponsive gel by introducing crosslinked methacrylated hyaluronic acid (HA-MA) networks into Pluronic F-127 (PF-127) gel (HP gel) to achieve sustained levofloxacin (LFX) delivery in bacterial keratitis treatment. The interactions between PF-127 molecules and HA-MA networks were studied by scanning electron microscopy, rheology, dynamic light scattering, differential scanning calorimetry, and small angle x-ray scattering. The results showed that the HP gel exhibited a higher critical gelling temperature and lower viscosity than the PF-127 gel (P gel), and could form a uniform thin layer on the ocular surface. Moreover, the drug release profile and gel dissolution rate revealed that the HA-MA network could retard the diffusion and dissolution of drug molecules and prolong the drug release time, which corresponded to an enhanced antibacterial ability of the HP-LFX gel. Furthermore, the HP gel exhibited low cytotoxicity to human corneal epithelial cells. Finally, an in vivo pharmacodynamic study was conducted with rabbit keratitis models. An improved treatment efficacy was observed after application of the HP-LFX gels. This study highlights the potential of HP gels in ophthalmic drug delivery.