Treating Bacterial Keratitis during Sleep through Placing Hydrogel Beads with Sustained Tobramycin/Baicalin Delivery Capability at the Palpebra Inferior

Simultaneously restricting bacterial proliferation while mitigating inflammatory reactions and excessive reactive oxygen species (ROS)-mediated corneal damage during sleep represents a crucial therapeutic strategy for managing bacterial keratitis (BK). In this study, we developed micron-scale PCBT hydrogel beads for nocturnal BK treatment by integrating two classical ophthalmic drugs: tobramycin (TOB) as the antibacterial component and baicalin (BA) as the anti-inflammatory/antioxidant agent. The formation of hydrogel beads was facilitated by the synergistic interplay between: (i) TOB solution-induced crystallization of chitosan (CS) chains and (ii) benzene-1,4-diboronic acid (1,4-BDBA) mediated ester crosslinking of polyvinyl alcohol (PVA) chains. TOB and BA were encapsulated within the hydrogel beads, with BA molecules grafted onto PVA chains via reversible phenylboronic acid ester bonds. When applied to the inferior palpebra, mechanical friction easily transformed the beads into a smooth/soft paste that sustainedly released therapeutic concentrations of TOB and BA for over 24 hours in simulated BK microenvironments. Inhibition zone assays, macrophage (Mφ) polarization analysis, and ROS scavenging tests collectively demonstrated the simultaneous antibacterial, anti-inflammatory and anti-oxidative properties of the hydrogel beads. A Staphylococcus aureus (S. aureus) infected cornea model in rabbits was employed to assess the clinical therapeutic potential of the hydrogel beads against BK during the sleep phase. The results of visual scoring, H&E staining, Masson staining, etc. indicated that the PCBT hydrogel beads exhibited superior therapeutic efficacy compared to conventional commercial eye drops, highlighting their promising application for BK treatment during nocturnal periods.