| Description |
Silver has a long history as an antimicrobial, and its use in clinical and consumer products continues to increase. Clinical silver biomaterials have achieved mixed rates of success while nanosilver consumer products in textiles, intranasal sprays, and oral liquid products are sold without significant research evaluating either safety or efficacy. Significantly, many products and research studies fail to characterize silver ion release from silver metallic coatings, compounds, and silver nanoparticles (AgNPs). Silver ion is proposed to act as the principal biologically active agent for both antibacterial activity and mammalian cell toxicity. Studies described in this dissertation seek to characterize AgNP dissolution in biological media, determine AgNP or released silver ion translocation across epithelial cells barriers, and evaluate AgNP use as a potential intranasal therapeutic to treat bacterial rhinosinusitis. First, an evaluation of the biodistribution and biocompatibility of an oral commercial colloidal silver product was performed on human subjects. Silver (not distinguishable between silver ion or AgNP forms) was detected in human blood circulation after 3-, 7-, and 14-day administrations with no adverse events reported. Next, AgNP dissolution was determined in biological media, and significant release of silver ion from AgNPs was observed. AgNP and AgNO3 translocation in human nasal epithelial cell monolayers and human ex vivo sinus tissue explants was evaluated and AgNO3 demonstrated significantly higher levels of translocation, reflecting ion preferential transport. AgNP internalization was observed in AgNP-exposed epithelial cell monolayer cultures by scanning transmission electron microscopy (STEM) and energy-dispersive x-ray spectroscopy (EDS). Finally, AgNPs were evaluated as a potential therapeutic to treat bacterial rhinosinusitis after intranasal delivery in mice. AgNO 3 demonstrated higher bactericidal activity against S. pneumoniae and significantly higher distribution of silver in the sinus tissue and blood than AgNPs. Results suggest that AgNPs would be an inadequate treatment for bacterial rhinosinusitis due to rapid clearance of silver from the sinus cavity after intranasal delivery of AgNPs. Released silver ion from AgNPs is concluded to be ostensibly responsible for all observed silver translocation through epithelium. These results are consistent with past studies that report released silver ion as the primary biologically active agent of AgNPs. |
