Zwitterionic silver nanoparticle based antibacterial eye drops for efficient therapy of bacterial keratitis

Abstract

Inefficient biofilm clearance and the risk of drug resistance pose significant challenges for antibiotic eye drops in the treatment of bacterial keratitis (BK). Recently, silver nanoparticles (AgNPs) have emerged as promising alternatives to antibiotics due to their potent antibacterial activity and minimal drug resistance. However, concerns regarding the potential biotoxicity of aggregated AgNPs in tissues have limited their practical application. In this study, polyzwitterion-functionalized AgNPs with excellent dispersion stability in the ocular physiological environment were chosen to prepare antibacterial eye drops. Zwitterionic AgNPs were synthesized using a copolymer, poly(sulfobetaine methacrylate-co-dopamine methacrylamide) (PSBDA), as a stabilizer and a reducing agent. The resulting antibacterial eye drops, named ZP@Ag-drops, demonstrated outstanding biocompatibility in in vitro cytotoxicity tests and in vivo rabbit eye instillation experiments, attributed to the zwitterionic PSBDA surface. Furthermore, the ZP@Ag-drops exhibited strong antibacterial activity against multiple pathogenic bacteria, particularly in penetrating and eradicating biofilms, due to the synergistic bactericidal effect of the released Ag⁺ and reactive oxygen species (ROS). Importantly, in vivo BK rabbit models showed that the ZP@Ag-drops effectively inhibited corneal infection and prevented ocular tissue damage, surpassing the therapeutic effect of commercial levofloxacin eye drops (LEV-drops). Overall, this study presents a promising alternative option for the effective treatment of BK using antibacterial eye drops.