Chitosan-Coated Silver-Vancomycin Nanoparticles for Treatment of Bacterial Endophthalmitis.

Abstract

PURPOSE: The rising incidence of drug-resistant ocular pathogens highlights the critical need for innovative therapeutic strategies. Here, we developed an antibacterial nanoformulation by combining silver with an antibiotic (vancomycin) and evaluated its efficacy using in vitro, ex vivo, and in vivo models of ocular Staphylococcus aureus infections. METHODS: Silver nanoparticles were synthesized through chemical reduction using silver nitrate and sodium citrate, subsequently loaded with vancomycin, and coated with chitosan to impart a positive surface charge. These nanoformulations were tested for their antimicrobial activity against S. aureus, including methicillin-resistant S. aureus (MRSA) and clinical isolates. The toxicity was evaluated in cultured human retinal Müller glia cells and mouse eyes. Ex vivo studies were performed using porcine/goat eyes and human vitreous. Therapeutic efficacy was evaluated in a mouse model of S. aureus endophthalmitis. RESULTS: Three formulations (AgNPs, CAgNPs, and CAgVNPs) ranged in size from 60 to 70 nm and demonstrated efficient vancomycin loading with controlled release in acidic conditions. Antimicrobial testing revealed synergistic antibacterial effects of nanoformulations against S. aureus, including MRSA and clinical isolates, resulting in a two- to fourfold reduction in minimum inhibitory concentration compared to vancomycin. Both in vitro and in vivo assays showed negligible cytotoxicity. All nanoformulations ameliorated the severity of S. aureus endophthalmitis, with CAgVNPs showing a marked reduction in bacterial burden (two- to sevenfold) and inflammatory cytokines (three- to fivefold). Moreover, CAgVNP-treated eyes exhibited reduced cell death and retinal tissue damage. CONCLUSIONS: Our study demonstrates that the synergistic activity of chitosan-coated silver nanoparticles and antibiotics represents a promising therapeutic strategy for treating resistant ocular bacterial infections.