Abstract
Purpose :
Ocular infections such as endophthalmitis and keratitis remain the leading cause of blindness, worldwide. Moreover, increasing antimicrobial resistance among ocular pathogens limit the treatment options. The aim of this study is to develop dual antibacterial nanoformulations using silver and antibiotics (vancomycin) and evaluate their antimicrobial efficacy against ocular pathogens.
Methods :
Silver nanoparticles were synthesized via a chemical reduction reaction with silver nitrate and sodium citrate. The nanoparticles were further loaded with vancomycin and coated with chitosan to give them a positive charge. Three different formulations, namely AgNPs, CAgNPs, and CAgVanNPs, were evaluated for their antimicrobial activity against gram-positive (S. aureus), gram-negative (P. aeruginosa), and fungal (C. albicans) pathogens. The toxicity and inflammatory response of all formulations were assessed in cultured human retinal Muller glia cells. The therapeutic efficacy of nanoparticles was evaluated in a mouse model of bacterial (S. aureus) endophthalmitis.
Results :
All nanoparticles had a size range of 60-70 nm and the chitosan coating resulted in a positive zeta potential. The vancomycin loading was ~80-90% with controlled drug release at acidic pH over five days. In vitro antimicrobial assays demonstrated potent killing activity against both sensitive and resistant strains of S. aureus. Similarly, CAgNPs had good penetration and killing effect against P. aeruginosa and C. albicans. Most importantly, nanoformulations had lower MIC values than vancomycin alone. Finally, silver nanoparticles were effective in alleviating endophthalmitis as evidenced by reduced bacterial burden and intraocular inflammation in S. aureus infected mouse eyes.
Conclusions :
Our study demonstrates that positive silver nanoparticles had broad-spectrum antimicrobial activity against ocular pathogens, including resistant strains. Moreover, they can synergize with antibiotics to reduce MIC, indicating their potential use for the treatment of ocular infections.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.