Deriving a provisional tolerable intake for intravenous exposure to silver nanoparticles released from medical devices.

Silver nanoparticles (AgNP) are incorporated into medical devices for their anti-microbial characteristics. The potential exposure and toxicity of AgNPs is unknown due to varying physicochemical particle properties and lack of toxicological data. The aim of this safety assessment is to derive a provisional tolerable intake (pTI) value for AgNPs released from blood-contacting medical devices. A literature review of in vivo studies investigating critical health effects induced from intravenous (i. v.) exposure to AgNPs was evaluated by the Annapolis Accords principles and Toxicological Data Reliability Assessment Tool (ToxRTool). The point of departure (POD) was based on an i. v. 28-day repeated AgNP (20 nm) dose toxicity study reporting an increase in relative spleen weight in rats with a 5% lower confidence bound of the benchmark dose (BMDL05) of 0.14 mg/kg bw/day. The POD was extrapolated to humans by a modifying factor of 1,000 to account for intraspecies variability, interspecies differences and lack of long-term toxicity data. The pTI for long-term i. v. exposure to 20 nm AgNPs released from blood-contacting medical devices was 0.14 µg/kg bw/day. This pTI may not be appropriate for nanoparticles of other physicochemical properties or routes of administration. The methodology is appropriate for deriving pTIs for nanoparticles in general.

Mitigation of SARS-CoV-2 by Using Transition Metal Nanozeolites and Quaternary Ammonium Compounds as Antiviral Agents in Suspensions and Soft Fabric Materials.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the need for novel, affordable, and efficient reagents to help reduce viral transmission, especially in high-risk environments including medical treatment facilities, close quarters, and austere settings. We examined transition-metal nanozeolite suspensions and quaternary ammonium compounds as an antiviral surface coating for various textile materials. Methods: Zeolites are crystalline porous aluminosilicate materials, with the ability of ion-exchanging different cations. Nanozeolites (30 nm) were synthesized and then ion-exchanged with silver, zinc and copper ions. Benzalkonium nitrate (BZN) was examined as the quaternary ammonium ion (quat). Suspensions of these materials were tested for antiviral activity towards SARS-CoV-2 using plaque assay and immunostaining. Suspensions of the nanozeolite and quat were deposited on polyester and cotton fabrics and the ability of these textiles towards neutralizing SARS-CoV-2 was examined. Results: We hypothesized that transition metal ion containing zeolites, particularly silver and zinc (AM30) and silver and copper (AV30), would be effective in reducing the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Additionally, AM30 and AV30 antiviral potency was tested when combined with a quaternary ammonium carrier, BZN. Our results indicate that exposure of SARS-CoV-2 to AM30 and/or AV30 suspensions reduced viral loads with time and exhibited dose-dependence. Antiviral activities of the combination of zeolite and BZN compositions were significantly enhanced. When used in textiles, AM30 and AV30-coated cotton and polyester fabrics alone or in combination with BZN exhibited significant antiviral properties, which were maintained even after various stress tests, including washes, SARS-CoV-2-repeated exposures, or treatments with soil-like materials. Conclusion: This study shows the efficacy of transition metal nanozeolite formulations as novel antiviral agents and establishes that nanozeolite with silver and zinc ions (AM30) and nanozeolite with silver and copper ions (AV30) when combined with benzalkonium nitrate (BZN) quickly and continuously inactivate SARS-CoV-2 in suspension and on fabric materials.

Silver nanoparticles: Significance of physicochemical properties and assay interference on the interpretation of in vitro cytotoxicity studies.

Silver nanoparticles (AgNPs) have generated a great deal of interest in the research, consumer product, and medical product communities due to their antimicrobial and anti-biofouling properties. However, in addition to their antimicrobial action, concerns have been expressed about the potential adverse human health effects of AgNPs. In vitro cytotoxicity studies often are used to characterize the biological response to AgNPs and the results of these studies may be used to identify hazards associated with exposure to AgNPs. Various factors, such as nanomaterial size (diameter), surface area, surface charge, redox potential, surface functionalization, and composition play a role in the development of toxicity in in vitro test systems. In addition, the interference of AgNPs with in vitro cytotoxicity assays may result in false negative or false positive results in some in vitro biological tests. The goal of this review is to: 1) summarize the impact of physical-chemical parameters, including size, shape, surface chemistry and aggregate formation on the in vitro cytotoxic effects of AgNPs; and 2) explore the nature of AgNPs interference in in vitro cytotoxicity assays.

Intracellular accumulation and dissolution of silver nanoparticles in L-929 fibroblast cells using live cell time-lapse microscopy.

Cytotoxicity assessments of nanomaterials, such as silver nanoparticles, are challenging due to interferences with test reagents and indicators as well uncertainties in dosing as a result of the complex nature of nanoparticle intracellular accumulation. Furthermore, current theories suggest that silver nanoparticle cytotoxicity is a result of silver nanoparticle dissolution and subsequent ion release. This study introduces a novel technique, nanoparticle associated cytotoxicity microscopy analysis (NACMA), which combines fluorescence microscopy detection using ethidium homodimer-1, a cell permeability marker that binds to DNA after a cell membrane is compromised (a classical dead-cell indicator dye), with live cell time-lapse microscopy and image analysis to simultaneously investigate silver nanoparticle accumulation and cytotoxicity in L-929 fibroblast cells. Results of this method are consistent with traditional methods of assessing cytotoxicity and nanoparticle accumulation. Studies conducted on 10, 50, 100 and 200 nm silver nanoparticles reveal size dependent cytotoxicity with particularly high cytotoxicity from 10 nm particles. In addition, NACMA results, when combined with transmission electron microscopy imaging, reveal direct evidence of intracellular silver ion dissolution and possible nanoparticle reformation within cells for all silver nanoparticle sizes.