Minimal In Vitro Antimicrobial Efficacy and Ocular Cell Toxicity from Silver Nanoparticles

Abstract

Silver in various forms has long been recognized for antimicrobial properties, both in biomedical devices and in eyes. However, soluble drugs used on the ocular surface are rapidly cleared through tear ducts and eventually ingested, resulting in decreased efficacy of the drug on its target tissue and potential concern for systemic side effects. Silver nanoparticles were studied as a source of anti-microbial silver for possible controlled-release contact lens controlled delivery formulations. Silver ion release over a period of several weeks from nanoparticle sources of various sizes and doses was evaluated in vitro against Pseudomonas aeruginosa strain PAO1. Mammalian cell viability and cytokine expression in response to silver nanoparticle exposure is evaluated using corneal epithelial cells and eye-associated macrophages cultured in vitro in serum-free media. Minimal microcidal and cell toxic effects were observed for several silver nanoparticle suspensions and aqueous extraction times for bulk total silver concentrations commensurate with comparative silver ion (e.g., \({\text{Ag}}_{\left( {{\text{aq}}} \right)}^ + \)) toxicity. This indicates that (1) silver particles themselves in these size ranges (20–60 nm diameter) are not microcidal under conditions tested, and (2) insufficient silver ion is generated from these particles at these silver ion-equivalent loadings to produce observable biological effects compared to silver ions in these in vitro assays. This is consistent with confounding literature describing both efficacy and lack of microcidal effects for silver nanoparticles, depending on milieu, surface oxide properties, and size. If dosing allows substantially increased silver particle loading in the lens to produce sufficient pathogen-toxic silver ions and/or particle-microbe direct contact, the bactericidal efficacy of silver nanoparticles in vitro could possibly limit bacterial colonization problems associated with extended-wear contact lenses.