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In Vivo Human Time-Exposure Study of Orally Dosed Commercial Silver Nanoparticles

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Abstract

Unlabelled: Human biodistribution, bioprocessing and possible toxicity of nanoscale silver receive increasing health assessment. We prospectively studied commercial 10- and 32-ppm nanoscale silver particle solutions in a single-blind, controlled, cross-over, intent-to-treat, design. Healthy subjects (n=60) underwent metabolic, blood counts, urinalysis, sputum induction, and chest and abdomen magnetic resonance imaging. Silver serum and urine content were determined. No clinically important changes in metabolic, hematologic, or urinalysis measures were identified. No morphological changes were detected in the lungs, heart or abdominal organs. No significant changes were noted in pulmonary reactive oxygen species or pro-inflammatory cytokine generation. In vivo oral exposure to these commercial nanoscale silver particle solutions does not prompt clinically important changes in human metabolic, hematologic, urine, physical findings or imaging morphology. Further study of increasing time exposure and dosing of silver nanoparticulate silver, and observation of additional organ systems are warranted to assert human toxicity thresholds. From the clinical editor: In this study, the effects of commercially available nanoparticles were studied in healthy volunteers, concluding no detectable toxicity with the utilized comprehensive assays and tests. As the authors rightfully state, further studies are definitely warranted. Studies like this are much needed for the more widespread application of nanomedicine.

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... Instead, silver could be detected in human serum. [124] Regarding the findings with rat and mice, several studies have been carried out to evaluate the effect of these nanoparticles on the gastrointestinal tract. An abnormal mucus composition of the intestines of the animals was observed, as well as pigmentation of the villi and discharge of mucus granules [102,103,109]. ...
... As can be seen in the aforementioned paragraphs, Ag-NPs have been shown to have toxic effects to both in in vitro and in vivo models; however, there is a limited number of studies that reported the impacts of Ag-NPs on human health. One of them is the one carried out by Munger et al. [124]. A total of 60 healthy subjects ingested nanoparticles at concentrations of 10 and 32 ppm (Ag-NPs size: 5-10 nm) for 14 days. ...
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Foodborne diseases are one of the factors that endanger the health of consumers, especially in people at risk of exclusion and in developing countries. The continuing search for effective antimicrobials to be used in the food industry has resulted in the emergence of nanotechnology in this area. Silver nanoparticles (Ag-NPs) are the nanomaterial with the best antimicrobial activity and therefore, with great potential of application in food processing and packing. However, possible health effects must be properly addressed to ensure food safety. This review presents a detailed description on the main applications of Ag-NPs as antimicrobial agents for food control, as well as the current legislation concerning these materials. Current knowledge about the impact of the dietary exposure to Ag-NPs in human health with special emphasis on the changes that nanoparticles undergo after passing through the gastrointestinal tract and how they alter the oral and gut microbiota, is also summarized. It is concluded that given their potential and wide properties against foodborne pathogens, research in Ag-NPs is of great interest but is not exempt from difficulties that must be resolved in order to certify the safety of their use.
... However, the safety for the use of Ag nanoparticles in the human body is still an important concern, as it has been reported that Ag nanoparticles could compromise cell viability and induce pathological damages in animal models [154]. In a clinical study reported by Munger, orally administered Ag nanoparticles (32 ppm) followed by a 2-week observation period presented no clinically important changes in metabolic, hematologic, or urinalysis measures [155]. There were also no detectable morphological changes in the lungs, heart or abdominal organs. ...
... There were also no detectable morphological changes in the lungs, heart or abdominal organs. ROS formation and subsequent pro-inflammatory cytokine generation commonly associated with Ag nanoparticles were not noted [155]. However, the chronic toxicity of Ag nanoparticles still remains to be further studied [156]. ...
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Clostridioides difficile, a spore-forming bacterium, is a nosocomial infectious pathogen which can be found in animals as well. Although various antibiotics and disinfectants were developed, C. difficile infection (CDI) remains a serious health problem. C. difficile spores have complex structures and dormant characteristics that contribute to their resistance to harsh environments, successful transmission and recurrence. C. difficile spores can germinate quickly after being exposed to bile acid and co-germinant in a suitable environment. The vegetative cells produce endospores, and the mature spores are released from the hosts for dissemination of the pathogen. Therefore, concurrent elimination of C. difficile vegetative cells and inhibition of spore germination is essential for effective control of CDI. This review focused on the molecular pathogenesis of CDI and new trends in targeting both spores and vegetative cells of this pathogen, as well as the potential contribution of nanotechnologies for the effective management of CDI.
... Ten to 12 weeks-old mice, 4 mice per group (two males and two females), were exposed to cit-AgNPs or PVP-AgNPs by oral gavage at a daily dose of 4 mg of Ag/kg for 7 consecutive days as in our previous studies (Nallanthighal et al., 2017a;Nallanthighal et al., 2017b), while control mice received water only. Allometric dose conversion of 4 mg/kg in a mouse yields 0.3 mg/ kg in an average (70 kg) human (Reagan-Shaw et al., 2008) and would correspond to AgNP intake after taking AgNP dietary supplements for 6 weeks (Munger et al., 2014). Dosing was performed between noon and 2 PM. ...
Article
Silver nanoparticles (AgNPs) are used in food packaging materials, dental care products and other consumer goods and can result in oral exposure. To determine whether AgNP coatings modulate transcriptional responses to AgNP exposure, we exposed mice orally to 20 nm citrate (cit)-coated AgNPs (cit-AgNPs) or polyvinylpyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) at a 4 mg/kg dose for 7 consecutive days and analyzed changes in the expression of protein-coding genes and long noncoding RNAs (lncRNAs), a new class of regulatory RNAs, in the liver. We identified unique and common expression signatures of protein-coding and lncRNA genes, altered biological processes and signaling pathways, and coding-non-coding gene interactions for cit-AgNPs and PVP-AgNPs. Commonly regulated genes comprised only about 10 and 20% of all differentially expressed genes in PVP-AgNP and cit-AgNP exposed mice, respectively. Commonly regulated biological processes included glutathione metabolic process and cellular oxidant detoxification. Commonly regulated pathways included Keap-Nrf2, PPAR, MAPK and IL-6 signaling pathways. The coding-non-coding gene co-expression analysis revealed that protein-coding genes were co-expressed with a variable number of lncRNAs ranging from one to twenty three and may share functional roles with the protein-coding genes. PVP-AgNP exposure induced a more robust transcriptional response than cit-AgNP exposure characterized by more than two-fold higher number of differentially expressed both protein-coding and lncRNA genes. Our data demonstrate that the surface coating strongly modulates the spectrum and the number of differentially expressed genes after oral AgNP exposure. On the other hand, our data suggest that AgNP exposure can alter drug and chemical sensitivity, metabolic homeostasis and cancer risk irrespective of the coating type, warranting further investigations.
... Recently, the toxic effect of AgNPs in humans was evaluated, with a daily intake of 100 µg day -1 (particles between 5 and 10 nm) and 480 µg day -1 (particles between 25 and 40 nm). The authors concluded that most of the silver detected in the blood was in the form of Ag + and that commercial AgNPs did not cause significant changes in human metabolism [266]. Another study monitored the possibility of Escherichia coli (K-12MG1655) acquiring resistance against AgNPs of 10 nm coated with citrate [267]. ...
Article
Nanotechnology is a cutting-edge area with numerous industrial applications. Nanoparticles are structures that have dimensions ranging from 1–100 nm which exhibit significantly different mechanical, optical, electrical, and chemical properties when compared with their larger counterparts. Synthetic routes that use natural sources, such as plant extracts, honey, and microorganisms are environmentally friendly and low-cost methods that can be used to obtain nanoparticles. These methods of synthesis generate products that are more stable and less toxic than those obtained using conventional methods. Nanoparticles formed by titanium dioxide, zinc oxide, silver, gold, and copper, as well as cellulose nanocrystals are among the nanostructures obtained by green synthesis that have shown interesting applications in several technological industries. Several analytical techniques have also been used to analyze the size, morphology, hydrodynamics, diameter, and chemical functional groups involved in the stabilization of the nanoparticles as well as to quantify and evaluate their formation. Despite their pharmaceutical, biotechnological, cosmetic, and food applications, studies have detected their harmful effects on human health and the environment; and thus, caution must be taken in uses involving living organisms. The present review aims to present an overview of the applications, the structural properties, and the green synthesis methods that are used to obtain nanoparticles, and special attention is given to those obtained from metal ions. The review also presents the analytical methods used to analyze, quantify, and characterize these nanostructures.
... Furthermore, in vivo oral exposure of AgNPs solutions at concentration of 10-and 32-ppm showed no clinical changes (in metabolic, hematologic, or urinalysis measures), and no morphological changes (in the lungs, heart or abdominal organs). Moreover, there were no significant changes in pulmonary reactive O 2 species or pro-inflammatory cytokine generation 45 . Therefore, AgNPs with well-controlled application in human body is still an active area of interdisciplinary research. ...
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Graphene based materials (GBMs) have potentials for dental and medical applications. GBMs may cause changes in the levels of cytokine released in the body. This study aimed to study the corrosion resistance of graphene oxide (GO) and GO/silver (GO/Ag) nanocomposite coated nickel-titanium (NiTi) alloy by electrophoretic deposition and to access the viability of human pulp fibroblasts, and the interleukin (IL)-6 and IL-8 expression level. The bare and coated NiTi samples were characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, surface profilometry, and X-ray diffraction (XRD). The corrosion resistance of the bare NiTi and coated NiTi samples were investigated by potentiodynamic polarization and electrochemical impedance spectroscopy in 3.5% NaCl solution. The cell viability of human pulp fibroblasts was accessed by the treated culture medium of the bare NiTi and coated NiTi alloys containing 1% fetal bovine serum. IL-6 and IL-8 expression levels were studied by human enzyme-linked immunosorbent assay (ELISA). Data were analyzed using One-way ANOVA (α = 0.05). Both the GO-coated NiTi and GO/Ag-coated NiTi alloys showed better corrosion resistance, a lower rate of corrosion, and higher protection efficiency than the bare NiTi alloy. The coated NiTi alloys were biocompatible to human pulp fibroblasts and showed upregulation of IL-6 and IL-8 levels.
... Their data suggested that AgNPs, applied as nanocrystalline silver dressing for four-to-six days, can penetrate beyond the stratum corneum and reach as deep as the reticular dermis. A controlled, cross over time exposure (three, seven, and 14 days) study of orally dosed (10 ppm) commercial AgNPs (5-10 nm) demonstrated the absence of any changes in human metabolic, hematologic, urine, and physical findings or imaging morphology [215]. However, AgNP toxicology research with respect to susceptible individual and human exposure thus far remains understudied, and these areas are particularly important with regard to NP risk assessment. ...
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Engineered nanomaterials (ENMs) have gained huge importance in technological advancements over the past few years. Among the various ENMs, silver nanoparticles (AgNPs) have become one of the most explored nanotechnology-derived nanostructures and have been intensively investigated for their unique physicochemical properties. The widespread commercial and biomedical application of nanosilver include its use as a catalyst and an optical receptor in cosmetics, electronics and textile engineering, as a bactericidal agent, and in wound dressings, surgical instruments, and disinfectants. This, in turn, has increased the potential for interactions of AgNPs with terrestrial and aquatic environments, as well as potential exposure and toxicity to human health. In the present review, after giving an overview of ENMs, we discuss the current advances on the physiochemical properties of AgNPs with specific emphasis on biodistribution and both in vitro and in vivo toxicity following various routes of exposure. Most in vitro studies have demonstrated the size-, dose- and coating-dependent cellular uptake of AgNPs. Following NPs exposure, in vivo biodistribution studies have reported Ag accumulation and toxicity to local as well as distant organs. Though there has been an increase in the number of studies in this area, more investigations are required to understand the mechanisms of toxicity following various modes of exposure to AgNPs.
... The majority of research in nanotoxicology has been focused on short term toxicity evaluation of nanoparticles. [1][2][3][4] Long-term exposure to nanoparticles can have adverse consequences that may not be observed in acute toxicity studies. When nanoparticles are administered in vivo, based on their body circulation time, biodistribution and the time needed for their degradation and elimination from the body, persistence of adverse effects can influence their long-term safety profile. ...
Article
Chronic toxicity evaluations of nanotechnology-based drugs are essential to support initiation of clinical trials. Ideally such evaluations should address the dosing strategy in human applications and provide sufficient information for long-term usage. Herein, we investigated one-year toxicity of non-surface modified silica nanoparticles (SNPs) with variations in size and porosity (Stöber SNPs 46 ± 4.9 and 432.0 ± 18.7 nm and mesoporous SNPs 466.0 ± 86.0 nm) upon single dose intravenous administration to female and male BALB/c mice (10 animal/sex/group) along with their human blood compatibility. Our evidence of clinical observation and blood parameters showed no significant changes in body weight, cell blood count, nor plasma biomarker indices. No significant changes were noted in post necropsy examination of internal organs and organ-to-body weight ratio. However, microscopic examination revealed significant amount of liver inflammation and aggregates of histiocytes with neutrophils within the spleen suggesting an ongoing or resolving injury. The fast accumulation of these plain SNPs in the liver and spleen upon i.v. administration and the duration needed for their clearance caused these injuries. There were also subtle changes which were attributed to prior infarctions or resolved intravascular thrombosis and included calcifications in pulmonary vessels, focal cardiac fibrosis with calcifications, and focal renal injury. Most of the pathologic lesions were observed when large, non-porous SNPs were administered. Statistically significant chronic toxicity was not observed for the small non-porous particles and for the mesoporous particles. This one-year post-exposure evaluation indicate that female and male BALB/c mice need up to one year to recover from acute tissue toxic effects of silica nanoparticles upon single dose intravenous administration at their 10-day maximum tolerated dose. Further, ex vivo testing with human blood and plasma revealed no hemolysis or complement activation following incubation with these silica nanoparticles. These results can inform the potential utility of silica nanoparticles in biomedical applications such as controlled drug delivery where intravenous injection of the particles is intended.
... For appropriate risk management of nano-formulations, it is necessary to follow the 'safety by design' principle in addition to significant administrative control to ensure a healthy and efficient work place (Vurro et al., 2019). The nanoparticle dose and the exposure duration should be considered when evaluating human toxicity thresholds (Munger et al., 2014). Research efforts should focus on the behavior and effects of nanomaterials (with clear descriptions of their composition, particle size, shape, aggregation behavior, surface area, and functionalization) in soil under different environmental conditions. ...
... However, to address the toxicity of nano silver, especially in therapeutics, Pauksch et al. (2014) studied the effects of AgNPs in bone cell metabolism and reported the dose dependent impairment of mesenchymal stem cells and osteoblasts at 10 µg/g, so the level below 10 µg/g should be used for therapeutic purpose. Further, Munger et al. (2014) reported that in vivo oral exposure of doses i.e., 10 and 32 ppm of AgNPs does not affect the healthy volunteers when examined for metabolic, hematologic, or urinalysis changes, they also didn't observed any morphological change in heart, lung or abdominal organs. Moreover, no change was also reported for pulmonary reactive oxygen species or pro-inflammatory cytokine generation. ...
Article
The evolving technology of nanoparticle synthesis, especially silver nanoparticle (AgNPs) has already been applied in various fields i.e., electronics, optics, catalysis, food, health and environment. With advancement in research, it is possible to develop nanoparticles of various size, shape, morphology, and surface to volume ratio utilizing biological systems. A number of different agents and methods can be employed to develop choice based AgNPs using algae, plants, fungi and bacteria. The use of plant extracts to produce AgNPs appears to be more convenient, as the method is simple, environmental friendly and inexpensive, also requiring a single-step. The microbial synthesis of AgNps showed intracellular and extracellular mechanisms to reduce metal ions into nanoparticles. Studies have shown that different size (1–100 nm) and shapes (spherical, triangular and hexagonal etc.) of nanoparticles can be produced from various biological routes and these diverse nanoparticles have various functions and usability i.e., agriculture, medical-science, textile, cosmetics and environment protection. The present review provides an overview of various biological systems used for AgNP synthesis, its underlying mechanisms, further highlighting the current research and applications of variable shape and sized AgNPs.
... On the other hand, Korani et al. studied the effect of silver nanoparticles in human health and showed a dose-dependent toxic response in several organs [81]. Munger et al. carried out a controlled, cross-over time exposure study of commercial silver nanoparticles, demonstrating the absence of any changes in human metabolic, hematologic, urine and physical findings or imaging morphology [82]. Balfourier et al. showed that gold nanoparticles could be metabolised by mammal cells, bringing an insight on the elimination of gold nanoparticles from organisms [50]. ...
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Biofilm-associated infections pose a huge burden on healthcare systems worldwide, with recurrent lung infections occurring due to the persistence of biofilm bacteria populations. In cystic fibrosis (CF), thick viscous mucus acts not only as a physical barrier, but also serves as a nidus for infection. Increased antibiotic resistance in the recent years indicates that current therapeutic strategies aimed at biofilm-associated infections are "failing", emphasizing the need to develop new and improved drug delivery systems with higher efficacy and efficiency. Magnetic nanoparticles (MNPs) have unique and favourable properties encompassing biocompatibility, biodegradability, magnetic and heat-mediated characteristics, making them suitable drug carriers. Additionally, an external magnetic force can be applied to enhance drug delivery to target sites, acting as "nano-knives", cutting through the bacterial biofilm layer and characteristically thick mucus in CF. In this review, we explore the multidisciplinary approach of using current and novel MNPs as vehicles of drug delivery. Although many of these offer exciting prospects for future biofilm therapeutics, there are also major challenges of this emerging field that need to be addressed.
... Short-term exposure to colloidal silver does not necessarily lead to immediate adverse effects. In a 14-day human study daily oral doses of 100 μg or 480 μg colloidal silver resulted in detectable silver concentrations in serum [28], but a wide range of clinical tests revealed no significant changes. However, when cytotoxicity of five commercial colloidal silver sprays was assessed in vitro, each of the products significantly decreased cell viability in a rat intestinal epithelial cell (IEC-6) model [29]. ...
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Aims The aim was to investigate the marketing practices, beliefs and health claims regarding the use of colloidal silver in Finland. Silver nanoparticles (AgNPs) are potentially toxic due to their small size and Ag⁺-release capabilities, and the use of colloidal silver products containing AgNPs can cause a wide variety of adverse effects such as argyria. Methods Contents of three company websites selling colloidal silver were reviewed, and the claims used in the marketing of colloidal silver were compared to the scientific information about silver. In Facebook posts and discussion about colloidal silver were analyzed. Results In Finland, the marketing of colloidal silver products on websites selling the products did not follow the regulations of authorities; several scientifically unfounded claims about the efficacy and medical use of colloidal silver were found. After the Finnish Broadcasting Company (Yle) documentary and an intervention by authorities, contents of the websites were changed, but still questionable information and misleading claims could be found. In the analyzed Facebook groups attitudes towards medical use of colloidal silver were uncritically positive, internal use was highly promoted and the restrictions of use were considered unjustified. Conclusions The use of quackery products such as colloidal silver can be dangerous, and their use and marketing should be controlled and restricted.
... [18][19][20][21][22] At the same time, it is generally accepted that mammals do not display a notable sensitivity to AgNPs in vivo. 23 This assumption alone justifies the wide use of AgNPs in various applications that incorporate contact with humans, and typically, no extensive toxicity tests are carried out. ...
Article
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Purpose: The ability of silver nanoparticles (AgNPs) of different sizes to influence copper metabolism in mice is assessed. Materials and methods: AgNPs with diameters of 10, 20, and 75 nm were fabricated through a chemical reduction of silver nitrate and characterized by UV/Vis spectrometry, transmission and scanning electronic microscopy, and laser diffractometry. To test their bioactivity, Escherichia coli cells, cultured A549 cells, and C57Bl/6 mice were used. The antibacterial activity of AgNPs was determined by inhibition of colony-forming ability, and cytotoxicity was tested using the MTT test (viability, %). Ceruloplasmin (Cp, the major mammalian extracellular copper-containing protein) concentration and enzymatic activity were measured using gel-assay analyses and WB, respectively. In vitro binding of AgNPs with serum proteins was monitored with UV/Vis spectroscopy. Metal concentrations were measured using atomic absorption spectrometry. Results: The smallest AgNPs displayed the largest dose- and time-dependent antibacterial activity. All nanoparticles inhibited the metabolic activity of A549 cells in accordance with dose and time, but no correlation between cytotoxicity and nanoparticle size was found. Nanosilver was not uniformly distributed through the body of mice intraperitoneally treated with low AgNP concentrations. It was predominantly accumulated in liver. There, nanosilver was included in ceruloplasmin, and Ag-ceruloplasmin with low oxidase activity level was formed. Larger nanoparticles more effectively interfered with the copper metabolism of mice. Large AgNPs quickly induced a drop of blood serum oxidase activity to practically zero, but after cancellation of AgNP treatment, the activity was rapidly restored. A major fraction of the nanosilver was excreted in the bile with Cp. Nanosilver was bound by alpha-2-macroglobulin in vitro and in vivo, but silver did not substitute for the copper atoms of Cp in vitro. Conclusion: The data showed that even at low concentrations, AgNPs influence murine copper metabolism in size-dependent manner. This property negatively correlated with the antibacterial activity of AgNPs.
... Indeed, ionic silver, which has been widely used in dentistry, is likely more toxic than nanoparticulated silver [139]. A study conducted with human volunteers [140] showed that a fourteen-day oral dosing of silver nanoparticles did not cause evident metabolic or hematologic changes, nor changes in urinalysis parameters, overall physical state, or imaging morphology. But it is noteworthy that the toxicity of 5 nm nanoparticles was described on human endothelial and bronchial epithelial cells [141], and this study used microarray analysis to show that AgNP-treated cells presented significant variations in cell death-, apoptosis-, and cell survival-related gene expression; however, 100 nm silver AgNPs did not induce cell death even at high concentrations, showing that AgNP toxicity is highly affected by the size of the nanoparticle. ...
Article
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Silver nanoparticles (AgNPs) have been successfully applied in several areas due to their significant antimicrobial activity against several microorganisms. In dentistry, AgNP can be applied in disinfection, prophylaxis, and prevention of infections in the oral cavity. In this work, the use of silver nanoparticles in dentistry and associated technological innovations was analyzed. The scientific literature was searched using PubMed and Scopus databases with descriptors related to the use of silver nanoparticles in dentistry, resulting in 90 open-access articles. The search for patents was restricted to the A61K code (International Patent Classification), using the same descriptors, resulting in 206 patents. The results found were ordered by dental specialties and demonstrated the incorporation of AgNPs in different areas of dentistry. In this context, the search for patents reaffirmed the growth of this technology and the dominance of the USA pharmaceutical industry over AgNPs product development. It could be concluded that nanotechnology is a promising area in dentistry with several applications.
... TiO 2 and Ag in male and female C57BL/6J mice in a 28-day oral exposure study with or without a 14-day post-exposure recovery period. TiO 2 and Ag are used in various consumer applications (Hadrup and Lam, 2014;Munger et al., 2014;Shakeel et al., 2016;Gajbhiye and Sakharwade, 2016;Rai and Shegokar, 2017). In the food sector, Ag NMs are used because of their antimicrobial and anti-odorant properties in food and water as well as in food packaging materials (FAO/WHO, 2010;Hadrup and Lam, 2014;Gunawan et al., 2017;Gaillet and Rouanet, 2015;Azeredo et al., 2019). ...
Article
In recent years, concerns have emerged about the potential neurotoxic effects of engineered nanomaterials (NMs). Titanium dioxide and silver are among the most widely used types of metallic NMs. We have investigated the effects of these NMs on behaviour and neuropathology in male and female C57BL/6 J mice following 28-day oral exposure with or without a 14-day post-exposure recovery. The mice were fed ad libitum with food pellets dosed with 10 mg/g TiO2, 2 mg/g polyvinylpyrrolidone-coated Ag or control pellets. Behaviour was evaluated by X-maze, open field, string suspension and rotarod tests. Histological alterations were analysed by immunohistochemistry and brain tissue homogenates were investigated for markers of oxidative stress, inflammation and blood-brain barrier disruption. Effects of the NMs on tyrosine and serine/threonine protein kinase activity in mouse brains were investigated by measuring kinase activity on peptide microarrays. Markers of inflammation, oxidative stress and blood-brain barrier integrity were not significantly affected in the male and female mice following exposure to Ag or TiO2. Both types of NMs also revealed no consistent significant treatment-related effects on anxiety and cognition. However, in the Ag NM exposed mice altered motor performance effects were observed by the rotarod test that differed between sexes. At 1-week post-exposure, a diminished performance in this test was observed exclusively in the female animals. Cortex tissues of female mice also showed a pronounced increase in tyrosine kinase activity following 28 days oral exposure to Ag NM. A subsequent Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) based toxicokinetic study in female mice revealed a rapid and persistent accumulation of Ag in various internal organs including liver, kidney, spleen and the brain up to 4 weeks post-exposure. In conclusion, our study demonstrated that subacute exposure to foodborne TiO2 and Ag NMs does not cause substantial neuropathological changes in mice. However, the toxicokinetic and specific toxicodynamic findings indicate that long-term exposures to Ag NM can cause neurotoxicity, possibly in a sex-dependent manner.
... The current available data from many research teams are insufficient, and some are even www.nature.com/scientificreports/ contradictory, to determine the adverse effects of metal nanoparticles on human health [39][40][41][42][43][44][45][46][47][48] . As the information of toxicological studies including bio-distribution and metabolism of nanosized particles are insufficient, the safe doses of Au-NP, Ag-NP and ZnO-NP for humans are not yet established by European Food Safety Authority (EFSA) or US Environmental Protection Agency (EPA). ...
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A metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ppm), ZnO-NP (60 ppm) and ClO2 (42.5 ppm) in aqueous solution was prepared and characterized by spectroscopy, transmission electron microscopy, dynamic light scattering analysis and potentiometric titration. Based on the in vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with effective concentration within the range to be used as food additives. TPNT1 was shown to block viral entry by inhibiting the binding of SARS-CoV-2 spike proteins to the angiotensin-converting enzyme 2 (ACE2) receptor and to interfere with the syncytium formation. In addition, TPNT1 also effectively reduced the cytopathic effects induced by human (H1N1) and avian (H5N1) influenza viruses, including the wild-type and oseltamivir-resistant virus isolates. Together with previously demonstrated efficacy as antimicrobials, TPNT1 can block viral entry and inhibit or prevent viral infection to provide prophylactic effects against both SARS-CoV-2 and opportunistic infections.
... Silver and silver nanoparticles are relatively nontoxic, supporting their wide application [15,16,18,286]. Lesions of the kidneys and lungs and arteriosclerosis have been attributed to both industrial and medicinal exposures [15]. Deposition of silver in renal glomerular basement membranes after high-level exposure may produce hypertension and possible cardiac complications [15,287]. ...
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Argyria encompasses the different cosmetic alterations that can develop if enough silver particles deposit in a specific tissue, typically in the skin, ranging from localized dark-blue macules to a generalized slate-gray/bluish tinge following systemic absorption. This work aims to fully review the state of the art regarding pathophysiology, diagnosis, treatment, and relevant clinical and forensic features of argyria. Argyria has been diagnosed in a wide range of ages, both sexes and varied ethnicities, with no known individual predisposing factors. Ultraviolet radiation with subsequence increases of melanin production aggravates the discoloration due to a reduction in the silver deposits. Physical examination and silver exposure in the anamnesis can be highly suggestive of the diagnosis, but a histopathological analysis with Energy-Dispersive X-ray Spectroscopy is required to unequivocally determine the discoloration etiology. Safe and effective treatment has only been accomplished with laser techniques, though only a few cases have been reported and with limited follow-up time. In conclusion, argyria typically has an occupational or iatrogenic etiology. It should be suspected when a patient presents with typical skin or eye lesions. A seemingly viable treatment modality, with laser technology, is finally within the horizon.
... Further, babies could also get exposed through AgNPs containing baby food products and oral care products (Ding et al. 2018). As per World Health Organization report (https:// www.who.int/water_sanitation_health/dwq/chemicals/silver.pdf), a median daily intake of silver through drinking water could range from 20 to 80 mg/day whereas, daily oral intake of AgNPs depends on the usage of AgNPs containing products (Hamilton and Minski 1973;Munger et al. 2014), and has not been explored well. Based on agyria development, World Health Organization has set a No Observable Adverse Effect Level (NOAEL) of 6.5 lg/kg bodyweight/day silver for the general population. ...
Article
Silver nanoparticles (AgNPs) are extensively utilized in food, cosmetics, and healthcare products. Though the effects of AgNPs exposure on adults are well documented, the long-term effects of gestational/perinatal exposure upon the health of offspring have not been addressed. Herein, we show that only perinatal exposure to AgNPs through the mother could lead to chronic inflammation in offspring which persists till adulthood. Further, AgNPs exposure altered offspring’s immune responses against environmental stresses. AgNPs exposed offspring showed an altered response in splenocyte proliferation assay when challenged to lipopolysaccharide, concanavalin-A, AgNPs, or silver ions. Perinatal AgNPs exposure affected metabolic parameters (resistin, glucagon-like peptide-1, leptin, insulin) and upregulated JNK/P38/ERK signaling in the pancreas. We observed pancreatic damage, reduced insulin level, and increased blood glucose levels. Further, we observed renal damage, particularly to tubular and glomerular regions as indicated by histopathology and electron microscopy. Our study thus shows that only perinatal exposure to AgNPs could induce persistent inflammation, alter immune responses against foreign antigens and metabolism which may contribute to pancreatic and renal damage later in life.
... Thus, AgNPs possess the outstanding potential for use in wound dressing applications. A controlled, cross over time exposure (3,7, and 14 days) study of orally dosed (10 ppm) commercial AgNPs (5-10 nm) demonstrated the absence of any changes in human metabolic, hematologic, urine, and physical findings or imaging morphology [53]. ...
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In this research work, nanofibrous hybrids are manufactured, characterized, and assessed as active antiviral and antibacterial membranes. In more detail, both polyvinyl alcohol (PVA) and thermoplastic polyurethane (TPU) nanofibrous (NF) membranes and their composites with embedded silver nanoparticles (Ag NPs) are manufactured by an electrospinning process. Their morphological structures have been investigated by a scanning electron microscope (SEM) which revealed a homogenous distribution and almost beads-free fibers in all manufactured samples. Characterization with spectroscopic tools has been performed and proved the successful manufacturing of Ag-incorporated PVA and TPU hybrid nanofibers. The crystalline phase of the nanofibers has been determined using an X-ray diffractometer (XRD) whose patterns showed their crystalline nature at an angle value (2θ) of less than 20°. Subsequent screening of both antiviral and antibacterial potential activities of developed nanohybrid membranes has been explored against different viruses, including SARS-Cov-2 and some bacterial strains. As a novel approach, the current work highlights potential effects of several polymeric hybrids on antiviral and antibacterial activities particularly against SARS-Cov-2. Moreover, two types of polymers have been tested and compared; PVA of excellent biodegradable and hydrophilic properties, and TPU of excellent mechanical, super elasticity, hydrophobicity, and durability properties. Such extreme polymers can serve a wide range of applications such as PPE, filtration, wound healing, etc. Consequently, assessment of their antiviral/antibacterial activities, as host matrices for Ag NPs, is needed for different medical applications. Our results showed that TPU-Ag was more effective than PVA-Ag as HIV-1 antiviral nanohybrid as well as in deactivating spike proteins of SARS-Cov-2. Both TPU-Ag and PVA-Ag nanofibrous membranes were found to have superior antimicrobial performance by increasing Ag concentration from 2 to 4 wt.%. Additionally, the developed membranes showed acceptable physical and mechanical properties along with both antiviral and antibacterial activities, which can enable them to be used as a promising functional layer in Personal Protective Equipment (PPE) such as (surgical gowns, gloves, overshoes, hair caps, etc.). Therefore, the developed functional membranes can support the decrease of both coronavirus spread and bacterial contamination, particularly among healthcare professionals within their workplace settings.
... At times, even changes in animal behavior were observed [95]. Research by de Lima et al. [96] and Munger et al. [97] showed that human cells are less susceptible to the toxic effects of silver nanoparticles. This suggests that the effects seen in animal studies may not occur in humans, and future studies should be conducted to confirm this finding. ...
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Issues arising in wound healing are very common, and chronic wound infections affect approximately 1.5% of the population. The main substances used in wound washing, cleansing and treatment are antiseptics. Today, there are many compounds with a known antiseptic activity. Older antiseptics (e.g., boric acid, ethacridine lactate, potassium permanganate, hydrogen peroxide, iodoform, iodine and dyes) are not recommended for wound treatment due to a number of disadvantages. According to the newest guidelines of the Polish Society for Wound Treatment and the German Consensus on Wound Antisepsis, only the following antiseptics should be taken into account for wound treatment: octenidine (OCT), polihexanide (PHMB), povidone-iodine (PVP-I), sodium hypochlorite (NaOCl) and nanosilver. This article provides an overview of the five antiseptics mentioned above, their chemical properties, wound applications, side effects and safety.
... Healthy volunteers were administered with 10 ppm and 32 ppm of silver nanoparticles ranging from sizes 10 nm to 40 nm respectively. This brings into attention the need for optimization of nanoparticle dosage in humans (Munger et al., 2014). ...
Article
The changes in lifestyle and living conditions have affected not only humans but also microorganisms. As man invents new drugs and therapies, pathogens alter themselves to survive and thrive. Multiple drug resistance (MDR) is the talk of the town for decades now. Many generations of medications have been termed useless as MDR rises among the infectious population. The surge in nanotechnology has brought a new hope in reducing this aspect of resistance in pathogens. It has been observed in several laboratory-based studies that the use of nanoparticles had a synergistic effect on the antibiotic being administered to the pathogen; several resistant strains scummed to the stress created by the nanoparticles and became susceptible to the drug. The major cause of resistance to date is the efflux system, which makes the latest generation of antibiotics ineffective without reaching the target site. If species-specific nanomaterials are used to control the activity of efflux pumps, it could revolutionize the field of medicine and make the previous generation resistant medications active once again. Therefore, the current study was devised to assess and review nanoparticles' role on efflux systems and discuss how specialized particles can be designed towards an infectious host's particular drug ejection systems.
... Aggregation of AgNPs may reduce their antimicrobial efficacy Liu et al., 2019a). Despite the concerns cytotoxicity and genotoxicity of AgNPs (Jena et al., 2012;Liu et al., 2017), no observed any clinically important differences in metabolic, urinary, hematologic, and physical measures, as well as no noticed changes in reactive oxygen species in the pulmonary or generation of pro-inflammatory cytokine when the administration of commercial colloidal silver nanoproduct orally (Munger et al., 2014(Munger et al., , 2015. A recent study indicated that AgNPs in vivo exerted a low degree of toxicity under the tolerable range which is well-tolerable at a moderate dose (Hussain et al., 2019). ...
Article
Biofilm represents one of the crucial factors for the emergence of multi-drug resistance bacterial infections. The high mortality, morbidity and medical device-related infections are associated with biofilm formation, which requires primarily seek alternative treatment strategies. Recently, nanotechnology has emerged as a promising method for eradicating bacterial biofilm-related infection. The efficacy of nanoparticles (NPs) against bacterial infections interest great attention, and the researches on the subject are rapidly increasing. However, the majority of studies continue to focus on the antimicrobial effects of NPs in vitro, while only a few achieved in vivo and very few registered as clinical trials. The present review aimed to organize the scattered available information regarding NPs approach to eradicate bacterial biofilm-related infections. The current review highlighted the advantages and disadvantages associated with this approach, in addition to the challenges that prevent reaching the clinical applications. It was appeared that the production of NPs either as antimicrobials or as drug carriers requires further investigations to overcome the obstacles associated with their kinetic and biocompatibility.
... Various studies have reported acute as well as chronic in vivo toxicity of different nanomaterials containing silver also [158,159]. Bioavailable silver ions reported as toxicity inducing agent in zebrafish embryos [160]. However, more in vivo cytotoxicity and genotoxicity of chemically produced AgNPs found than green synthesized AgNPs which suggests green synthesized AgNPs are less toxic and biologically compatible than chemically synthesized one [161]. ...
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With the breakthrough in advance technologies, researchers are looking to devise novel approaches to control different types of deadly cancers. Progress in medicinal plants research and nanotechnology has drawn scientist's attention toward green synthesis of metallic nanoparticles by exploiting plants secondary metabolites owing to its advantage over routinely used physical and chemical synthesis (simple, one step approach to reduce and stabilize bulk silver into silver nanoparticles (AgNPs), cost effectiveness, energy efficient, biocompatibility and therapeutic significance). Owing to control size, shape and functional surface corona, AgNPs hold considerable potentiality for therapeutic applications by opting different mechanistic pathways such as mitochondrial disruption, DNA fragmentation, cell membrane disruption, interruption of cellular signaling pathways, altered enzyme activity and reactive oxygen species (ROS) production leading to apoptosis etc In this review, we discussed the green synthesized AgNPs in the possible cancer treatment by harnessing phytochemicals present in plant extract. In addition, this review also provides recent advances and achievements in utilization of green synthesized AgNPs in cancer treatment and proposes mechanistic action for their anticancer and cytotoxic potential. By understanding the mechanistic action of AgNPs responsible for their therapeutic efficacy will help to devise customized therapies and treatment against cancer as a potential cancer therapeutic tool.
... It was found that not all the drug formulas under investigation culminated in any detectable signs of toxicity. In this context, Ag-NPs recorded no cytotoxic effects on human cells at concentrations below 30 mg/l (Krajewski et al., 2013;Munger et al., 2014). Also, the hemolytic activity of Ag-NPs on human erythrocytes was examined by Katva et al. (2018) and recorded that 10-100 µg/ml concentration of Ag-NPs didn't induce any hemolysis of blood cells, including erythrocytes. ...
... It was found that not all the drug formulas under investigation culminated in any detectable signs of toxicity. In this context, Ag-NPs recorded no cytotoxic effects on human cells at concentrations below 30 mg/l (Krajewski et al., 2013;Munger et al., 2014). Also, the hemolytic activity of Ag-NPs on human erythrocytes was examined by Katva et al. (2018) and recorded that 10-100 µg/ml concentration of Ag-NPs didn't induce any hemolysis of blood cells, including erythrocytes. ...
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Burn wound infections with multidrug-resistant (MDR) bacteria are shown in many countries as severe widespread health threats. Consequently, attention has been devoted to new nanoparticle-based materials in the field of antimicrobial chemotherapy for burn wound infections. This study aimed to evaluate both in vitro and in vivo efficacies of nanoparticle-antibiotic combinations as new classes of materials subjected against MDR Pseudomonas aeruginosa. Out of 40 Gram-negative isolates, 23 P. aeruginosa were recovered from patients with burn wound infections attending different hospitals in Tanta, Egypt. The susceptibility test revealed that 95.7% of P. aeruginosa isolates were MDR with a high incidence of resistance against carbenicillin. Antibacterial activities of silver nanoparticles (Ag-NPs) against the isolates examined showed various inhibition zone diameters ranging from 11 to 17 mm. Strong synergistic efficacy of neomycin was reported in combination with Ag-NPs against MDR P. aeruginosa P 8 and P 14 isolates. The in vivo effectiveness of various pharmaceutical formulations prepared from a combination of neomycin antibiotic with Ag-NPs in the treatment of induced bacterially infected mice burns showed that maximum healing activity along with faster wound contraction reported with the combination of neomycin-Ag-NPs in the spray formulation. Generally, data indicated that incorporating Ag-NPs in combination with certain antibiotics may be a new, promising application for wound treatments, especially burns infected with MDR P. aeruginosa.
... However, some studies have proved a different opinion. Munger et al. [64] conducted an in vivo study with two concentrations (10 ppm and 32 ppm) of commercial AgNPs solution over a 3-14 day-monitored human exposure. No clinically significant toxic effects were observed except that silver was detected in human serum. ...
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The contamination of dental unit waterlines (DUWLs) is a major health concern since it can pose cross-infection risks among dental professionals and their patients. Silver is one of the widely used metals in medical fields due to its superior antimicrobial properties. Silver-based agents have been commercially available for the decontamination of dental unit water currently. This systematic review aims to examine the evidence supporting efficacy and safety of application of silver to decontaminate DUWLs. We performed a search of the peer-review literature of studies in six electronic databases using corresponding search terms. Eligibility was restricted to English-language studies exploring the application of silver to decontaminate dental unit water, e.g., silver-based disinfectants and silver-coated dental waterlines tubing. The search identified 148 articles, and 9 articles that met the criteria were synthesized with qualitative narrative analyses. We observed good evidence of antimicrobial efficacy of silver with hydrogen peroxide on diverse microorganism present in DUWLs. Furthermore, there is insufficient evidence on the application of silver nanoparticles (AgNPs) as an efficient material to control the biofilms in DUWLs. Post-treatment data of either the bactericidal and bacteriostatic effects of silver or AgNPs, especially the actual clinical efficacy of long-term application, are scarce. More high-quality research is needed to resolve the gap on the optimal dosage and treatment options required to control bacterial and biofilm in DUWLs with silver-containing materials.
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There is growing concern about the potential adverse effects of oral exposure to engineered nanomaterials (ENM). Recent years have witnessed major developments in and advancement of intestinal in vitro models for nanosafety evaluation. The present paper reviews the key factors that should be considered for inclusion in nonanimal alternative testing approaches to reliably reflect the in vivo dynamics of the physicochemical properties of ENM as well the intestinal physiology and morphology. Currently available models range from simple cell line-based monocultures to advanced 3D systems and organoids. In addition, in vitro approaches exist to replicate the mucous barrier, digestive processes, luminal flow, peristalsis, and interactions of ENM with the intestinal microbiota. However, while the inclusion of a multitude of individual factors/components of particle (pre)treatment, exposure approach, and cell model approximates in vivo-like conditions, such increasing complexity inevitably affects the system's robustness and reproducibility. The selection of the individual modules to build the in vitro testing strategy should be driven and justified by the specific purpose of the study and, not least, the intended or actual application of the investigated ENM. Studies that address health hazards of ingested ENM likely require different approaches than research efforts to unravel the fundamental interactions or toxicity mechanisms of ENM in the intestine. Advanced reliable and robust in vitro models of the intestine, especially when combined in an integrated testing approach, offer great potential to further improve the field of nanosafety research.
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The use of colloidal silver-containing products as dietary supplements, immune boosters and surface disinfectants has increased in recent years which has elevated the potential for human exposure to silver nanoparticles and ions. Product mislabeling and long-term use of these products may put consumers at risk for adverse health outcomes including argyria. This study assessed several physical and chemical characteristics of five commercial products as well as their cytotoxicity using a rat intestinal epithelial cell (IEC-6) model. Concentrations of silver were determined for both the soluble and particulate fractions of the products. Primary particle size distribution and elemental composition were determined by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. Hydrodynamic diameters were measured using nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). The effect of gastrointestinal (GI) simulation on the colloidal silver products was determined using two systems. First, physical and chemical changes of the silver nanoparticles in these products was assessed after exposure to Synthetic Stomach Fluid (SSF) resulting in particle agglomeration, and the appearance of AgCl on the surfaces and between particles. IEC-6 cells were exposed for 24 h to dilutions of the products and assessed for cell viability. The products were also treated with a three-stage simulated GI system (stomach and intestinal fluids) prior to exposure of the IEC-6 cells to the isolated silver nanoparticles. Cell viability was affected by each of the consumer products. Based on the silver nitrate and commercial silver nanoparticle dose response, the cytotoxicity for each of the colloidal silver products was attributed to the particulate silver, soluble silver or non‑silver matrix constituents.
Chapter
This chapter provides an overview of the potential human health and environmental impact of nanomaterials (NMs). These unique materials can be produced naturally, incidentally or manufactured and can have numerous effects on human and ecological health. From the perspective of human health, the ultra-small nature of NMs can cause them to be highly reactive and promote adverse interactions at the organ, tissue, and cellular levels. Ecologically, NMs have the potential to pass into the environment at each point in their life cycle. Within the environment NMs undergo chemical, physical or biological processes that will modify their environmental fate and biological effects. The toxicological issues broadly covered in this chapter are discussed in further detail throughout this book.
Chapter
Microorganisms develop resistance to antimicrobial compounds, which is an important global health threat. As per the World Health Organization (WHO) report, antimicrobial resistance (AMR) is one of the leading causes of mortality worldwide. To overcome antibiotic resistance, nanoscale antimicrobial agents can be used as an alternative strategy. Different types of nanoparticles (NP) such as solid lipid (SL) NPs, liposomal NPs, polymer-based NPs, inorganic NPs, magnetic NPs, mesoporous silica NPs, and carbon nanomaterials are used for drug delivery. Metal nanoparticles (NPs) such as copper (Cu), titanium (Ti), silver (Ag), gold (Au), and zinc (Zn) have antimicrobial activity. The antimicrobial properties of NPs depend on size, chemical composition, and shape of these NPs. The present chapter reviews the application of various nanoparticles as antimicrobial agents and their potential application against multidrug-resistant microbial pathogens in public health. Advancement in nanomedicine is an important aspect for diagnosis and treatment of diseases induced by drug-resistant microorganisms.
Article
Despite significant progress made in the past two decades, silver nanoparticles (AgNPs) have not yet made it to the clinical trials. In addition, they showed both positive and negative effects in their toxicity from unicellular organism to well-developed multi-organ system, for example, rat. Although it is generally accepted that capped (bio)molecules have synergistic bioactivities and diminish the toxicity of metallic Ag core, convincing evidence is completely lacking. Therefore, in this review, we first highlight the recent in vivo toxicity studies of chemically manufactured AgNPs, biologically synthesized AgNPs and reference AgNPs of European Commission. Then, their toxic effects are compared with each other and the overlooked factors leading to the potential conflict of obtained toxicity results are discussed. Finally, suggestions are given to better design and conduct the future toxicity studies and to fast-track the successful clinical translation of AgNPs as well.
Article
Escherichia coli (E Coli) biofilms are a major causative agent of many intestinal infections and there is ongoing research aimed at E Coli biofilm eradication. Gold nanoclusters (AuNCs) conjugated with various surface ligands have been extensively investigated for antimicrobial properties and provide a potential solution. There is little known about their in vivo safety because current standards of nanosafety research involves incubation of AuNCs with cells in vitro to confirm biocompatibility. In addition to systemic administration, nanosafety research on AuNC-based antimicrobials designed to treat gastrointestinal infections must also consider the potential for inducing gastrointestinal disorders. We report the design and application of two AuNCs coated with either hydroxyl ([email protected]) or amine ([email protected]) functionalized polyethylene glycol, which enables the eradication of E coli biofilms. Gastrointestinal safety of [email protected] and [email protected] was evaluated in healthy mice up to 35 days after administration by oral gavage at a dose of 10 mg/kg (or 1 mg/mL) daily for 14 days. No changes were detected in the major organs histopathology, serum chemistry, hematology and feces. Thus, oral administration of AuNCs is unlikely to be of concern for systemic toxicity or in the induction of gastrointestinal illnesses. Further studies of increasing time exposure and doses are necessary to determine if toxicity occurs at higher doses or if there is no adverse effects limit.
Article
The growing evidence of the microbiome’s crucial role in human health and disease has prompted research on understanding the impacts of engineered nanomaterials (ENMs) on commensal microorganisms. Accordingly, the number of studies addressing the ENM effects on intestinal microbiota has been rapidly increasing over the past few years. The focus on the gut microbiota is justified due to established metabolic and immunological functions of gut microbes, however, respiratory tract and skin microbiota also play important roles in host health and immunity. Here we review the composition and functions of microbiota inhabiting the major human organs that are prone to ENM exposure – skin, respiratory and digestive tract. We discuss the mechanisms of ENM actions relevant to physiological conditions and microbiota, and describe recently developed in vitro models for elucidating the ENM impacts on the gut microbiota. We find that studies pertinent to the oxygen levels prevailing in the digestive tract, are still limited. Finally, we analyze the results of in vivo studies conducted in vertebrate models – zebrafish, mice and rats – exposed to ENMs via ingestion. The relative abundances of bacterial phyla indicate that ENMs have a potential to modulate intestinal microbiota and induce harmful or beneficial effects in the host. Future perspectives include identification of the factors driving ENM-caused dysbiosis and the ENM impacts on microbiota with deviated composition, e.g., under compromised health conditions. Understanding the interplay between ENMs and the human microbiota is crucial for the continued development of nanomedicine and protection of human health against accidental exposure to hazardous ENMs.
Article
Nanoparticles from natural and anthropogenic sources are abundant in the environment, thus human exposure to nanoparticles is inevitable. Due to this constant exposure, it is critically important to understand the potential acute and chronic adverse effects and toxicity that nanoparticles may cause to humans. In this review, we explore and highlight the current state of nanotoxicology research with a focus on mechanistic understanding of nanoparticle toxicity at organ, tissue, cell, and biomolecular levels. We discuss nanotoxicity mechanisms, including generation of reactive oxygen species, nanoparticle disintegration, modulation of cell signaling pathways, protein corona formation, and poly(ethylene glycol)-mediated immunogenicity. We conclude with a perspective on potential approaches to advance current understanding of nanoparticle toxicity. Such improved understanding may lead to mitigation strategies that could enable safe application of nanoparticles in humans. Advances in nanotoxicity research will ultimately inform efforts to establish standardized regulatory frameworks with the goal of fully exploiting the potential of nanotechnology while minimizing harm to humans. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Chapter
The surge in nanobiotechnology has given rise to successful utilization of nanoparticles in several novel applications in agriculture, industry, and the biomedical field. However, nanoparticles have a more pronounced effect in systems with respect to inflammation and cell damage as compared to an equal mass of particles having greater size. They are known to induce pulmonary, cutaneous, cardiovascular, and xenotoxicity. The engineered nanoparticles, owing to their high reactivity, have the capacity to initiate inflammatory responses that act as a trigger for metastasis. Huge knowledge gaps exist with respect to the nature of nanoparticles and their interaction with different environmental components. Apart from beneficial reports, there have been numerous studies implicating nanoparticles in plant toxicity through chromosomal abnormalities, oxidative damages to biological membranes, decreased photosynthetic rate, growth retardation, reduction in seed germination, biomass, leaf number, root elongation, and even plant death.
Article
Recently, with the developments in the field of nanotechnology, silver nanoparticles (AgNPs) have become one of the most fascinated nanoparticles by virtue of their multifarious applications in wide array of disciplines. AgNPs hold unique physical, chemical, and biological properties which determine their suitability in these applications. The synthesis of AgNPs using the principles of green chemistry in contrast to other methods is not only eco-friendly and cost-effective, but the nanoparticles thus formed are also biocompatible. AgNPs produced by such means express certain unique characteristics which allow them to be used as antimicrobial, antifungal, antiviral, and anticancer agents. Moreover, natural catalytic action for degradation of pollutants, usefulness in treatment of diabetes-related complications, and wound healing properties make AgNPs even more valuable. A lot of work has been done on AgNPs in the past, hence a comprehensive review article will be more beneficial for the readers and futuristic work. Therefore, the present review article is aimed to provide a detailed study of various biological methodologies employed in synthesis of AgNPs, their characteristics, and applications in various fields.Graphical abstract
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Cancer is a collection of ailments that severely affect the cellular metabolism established due to anomalous signaling mechanisms including cell proliferation, angiogenesis, and metastasis. Biogenic nanoparticles due to their efficacy, cost-effectiveness, and green nature provide an alternate paradigm to cancer theranostics. In this chapter we will discuss the underlying mechanisms via which biogenic metal nanoparticles exert their anticancer action. Foreseeing the challenges, we expect that biogenic metal nanoparticles can be developed as prospective cancer theranostic agents in the near future.
Chapter
This chapter deals with the miscellaneous approaches of chemoprevention including synthetic chemicals, vitamins, NSAIDs, antioxidants, etc. Role of silver nanoparticles and selenium nanoparticles is also described in chemoprevention. A section on combination therapies using both phytopharmaceuticals and synthetic anticancer drugs is also added. The reports on simultaneous use of diagnostic agent with chemopreventive agents are further described in the chapter.
Book
The SCCS adopted this document by written procedure on 5 March 2021 (49 Pages) Mise en ligne le 5 Mars 2021 https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_245.pdf
Article
Background We are trying to evaluate silver nanoparticles’ effectiveness (SilvrSTAT Gel) in accelerating healing rate of nonischemic diabetic foot ulcers (DFUs). Methods This prospective, double-blind, randomized, controlled study includes 80 patients with nonischemic DFUs classified into 2 groups. Group A was subjected to SilvrSTAT Gel dressing, and group B was subjected to conventional dressing (wet-to-moist dressing with or without povidone-iodine). All cases had minimal debridement before treatment. In both groups, all cases were nonischemic after successful revascularization either by bypass surgery or endovascular therapy. Results The healing rate of the SilvrSTAT group was significantly higher than that of the conventional group. The healing rate per week of the SilvrSTAT group was considerably higher than that of the conventional group ( P < .0001). The rate of complete healing for ulcers in group A was achieved in 22 patients (55%) by the 6th week, while 29 (72.5%), 34 (85%), and 36 (90%) patients were healed entirely by the 8th, 10th, and 12th weeks, respectively. In group B: 20 (50%), 27 (67.5%), and 30 (75%) patients were completeley healed by the 8th, 10th, and 12th weeks, respectively. Conclusions SilvrSTATGel is effective in the treatment of DFU.
Article
Amorphous forms of silica have always raised a lot of interest by the scientific community and are nowadays rapidly growing in commercial applications. These are commercialized as aerogels or as nanoparticles, which can feature many similarities, not only in the synthesis process but also because clusters of nanoparticles are commonly released from aerogels. Nevertheless, the health effects of amorphous silica materials are not fully understood, as occurs with many other nanoforms. Amorphous silica is known to be less toxic than its crystalline form, but toxicity studies, regulatory aspects and handling practices are still scarce. In this work, the knowledge on toxicity of amorphous silica nanostructures and suitable regulations are reviewed. Furthermore, relevant safety practices for handling these materials are discussed and strategies used to recycle and dispose them are summarized.
Chapter
SilverSol® is a unique nano-silver preparation formulated by American Biotech Labs (ABL), USA, in varied dosage forms (liquid, gel, cream, toothpaste etc.), with proven efficacy as an antimicrobial and antiviral product. SilverSol® is produced using a patented technology that uniquely captures silver’s antimicrobial activity effectively. The individual silver nanoparticle (NP) contains elemental (zero-valent) metallic silver coated with silver oxide and has an optimum particle size ranging from 5 to 50 nm. The technology achieves unique tetrahedral molecular arrangement of silver with oxygen, giving rise to a broad range of properties. The key properties of SilverSol®, viz. multidimensional efficacy at extremely low concentration, prolonged stability and absence of adverse side effects make it ‘the product of choice’ in wound healing. Several products of SilverSol® both for oral administration and topical application are available world-wide in gel, liquid and cream form and other application-oriented forms. These products are outstanding with proven efficacy in various ailments besides wound healing viz. malaria, various bacterial, fungal, viral infections including HIV, influenza virus, vaginal infection, severe infectious conditions due to resistant bacteria—MRSA (Methicillin Resistant Staphylococcus aureus) and VRE (Vancomycin Resistant Enterococci). The current review focuses on its most widely accepted use as a wound healing agent, both for external applications and for oral administration. It also gives detailed attributes of SilverSol® in terms of safety, efficacy and pharmacology. Its physicochemical properties, mechanism of action and its regulatory status are also described. Several wounds of varied etiology and severity have been successfully treated with SilverSol® without the formation of dermal fibrotic lesions, demonstrating its efficacy in wound healing. It has been proven to be beneficial in 55,000 dental surgeries with varied case histories. Remarkable effects were associated with less post-operative/surgical pain and oedema, less post-operative complications, prevention of bacterial and fungal infection and removal of biofilms, which collectively resulted into quicker healing.
Article
Employing new strategies to develop novel composite systems has become a popular area of interest among researchers. Raising people's awareness and their attention to the health and safety issues are key parameters to achieve this purpose. One of the recommended strategies is the utilization of nanoparticles within the matrix of composite materials to improve their physical, mechanical, structural and antimicrobial characteristics. Silver nanoparticles (Ag NPs) have attracted much attention for nanocomposite applications mainly due to their antimicrobial characteristics. Herein, the current review will focus on the different methods for preparing antimicrobial nanocomposites loaded with Ag NPs, the release of Ag NPs from these nanostructures in different media, analyzing techniques for the evaluation of Ag release from nanocomposites, potential applications, and safety issues of nanocomposites containing Ag NPs. The applications of Ag NPs-loaded nanocomposites have been extensively established in food, biomedical, textile, environmental and pharmacological areas mainly due to their antibacterial attributes. Several precautions should be addressed before implementation of Ag NPs in nanocomposites due to the health and safety issues.
Article
Two silver-polyaniline/polyvinylpyrrolidone (Ag-PANI/PVP) nanocomposites were prepared using in situ integration of silver nanoparticles (AgNPs) during oxidative aniline polymerization, accelerated by the presence of PVP, which as well minimized the risk...
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Recent studies with silver nanoparticles (AgNPs) and the history of silver metal as a broad-spectrum bactericidal and virucidal agent, places silver as one of the future biocidal candidates in the field of nanomedicine to eliminate bacteria and viruses, especially multidrug resistant ones. In this review, we have described the various morphologies of AgNPs and correlated the enhanced bactericidal activity with their prominent {111} facets. In addition to prioritizing the characterization we have also discussed the importance of quantifying AgNPs and silver ion content (Ag ⁺ ) and their different mechanisms at the chemical, biological, pharmacological, and toxicological levels. The mechanism of action of AgNPs against various bacteria and viruses including the SARS-CoV-2 was analyzed in order to understand its effectiveness as an antimicrobial agent with therapeutic efficacy and low toxicity. Further, there is the need to characterize AgNPs and quantify the content of free Ag ⁺ for the implementation of new systematic studies of this promising agent in nanomedicine and in clinical practice.
Book
Biogenic Nanoparticles for Cancer Theranostics outlines the synthesis of biogenic nanoparticles to become cancer theranostic agents. The book also discusses their cellular interaction and uptake, pharmacokinetics, biodistribution, drug delivery efficiency, and other biological effects. Additionally, the book explores the mechanism of their penetration in cancerous tissue, its clearance, and its metabolism. Moreover, the in vitro and in vivo toxicological effects of biogenic nanoparticles are discussed. This book is an important reference source for materials scientists and biomedical scientists who are looking to increase their understanding of how biogenic nanoparticles are being used for a range of cancer treatment types. Metal nanoparticles have traditionally been synthesized by classical physico-chemical methods which have many drawbacks, such as high energy demand, high cost and potential ecotoxicity. As a result, the biosynthesis of metal nanoparticles is gaining increasing prominence. Biosynthesis approaches to metal nanoparticles are clean, safe, energy efficient and environment friendly.
Although extensive research has shown the pathological effect of fine and ultrafine airborne particles, clear evidence of association of environmental exposure to them and inflammatory changes in human nasal mucosa is missing. Meanwhile, pathogenesis of chronic rhinosinusitis, despite being a disease with high prevalence in the population, is still unclear. The increasing evidence of the pro-inflammatory properties of these particles raises the question of their possible role in chronic rhinosinusitis. The presented study focused on detection of microsized anorganic particles and clusters of nanosized anorganic particles in the nasal mucosa of patients with chronic rhinosinusitis by Raman microspectroscopy and comparison of their composition to histologic findings. The results were compared to the findings in mucosa obtained from cadavers with no history of chronic rhinosinusitis. Solid particles were found in 90% of tissue samples in the group with chronic rhinosinusitis, showing histologic signs of inflammation in 95%, while in the control group, the particles were found in 20% of samples, with normal histologic findings in all of them. The main detected compounds were graphite, TiO2, amorphous carbon, calcite, ankerite and iron compounds. The results are in accordance with the premise that exogenous airborne particles interact with the nasal mucosa and possibly deposit in it in cases where the epithelial barrier is compromised in chronic rhinosinusitis.
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We first establish the literature on the use of ultradilute aquasols as extraordinary, powerful, bactericidal inorganic agents equal to most commercial antibiotics. These findings provide the rationale for a major role for inorganic materials scientists to contribute the insights unique to their field for new, safer health vectors. The focus of this preliminary paper is exclusively on the materials science of 2-phase stable sols at ultradilute concentrations near 1 at.-ppm. We analyze the solid and liquid phases for the first time in detail using standard materials science analysis tools. The solid phase is analyzed using DTA, TGA, XRD, SEM, and TEM, and the liquid water phase is analyzed using FTIR, UV-VIS, and Raman spectroscopy. There are at least three crystalline phases in the system Ag-O: Ag, Ag2O, and Ag4O4, which are stable in air. In an aqueous environment between 0 and 100uC there is evidence that various combinations of metal, oxides, and possible 'oxy-hydroxide' complexes exist. Similarly, data from Raman and UV-VIS spectroscopy show definite changes in the structure of the water host. These results, in a preliminary way, are parallel to the many empirical observations made by physicians for the last 100 years on the use of metallic silver and water in various combinations for human health.
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Environmental particulate matter (PM) pollutants adversely affect human health, but the molecular basis is poorly understood. The ion channel transient receptor potential vanilloid-1 (TRPV1) has been implicated as a sensor for environmental PM and a mediator of adverse events in the respiratory tract. The objectives of this study were to determine whether TRPV1 can distinguish chemically and physically unique PM that represents important sources of air pollution; to elucidate the molecular basis of TRPV1 activation by PM; and to ascertain the contributions of TRPV1 to human lung cell and mouse lung tissue responses exposed to an insoluble PM agonist, coal fly ash (CFA1). The major findings of this study are that TRPV1 is activated by some, but not all of the prototype PM materials evaluated, with rank-ordered responses of CFA1 > diesel exhaust PM > crystalline silica; TRP melastatin-8 is also robustly activated by CFA1, whereas other TRP channels expressed by airway sensory neurons and lung epithelial cells that may also be activated by CFA1, including TRPs ankyrin 1 (A1), canonical 4α (C4α), M2, V2, V3, and V4, were either slightly (TRPA1) or not activated by CFA1; activation of TRPV1 by CFA1 occurs via cell surface interactions between the solid components of CFA1 and specific amino acid residues of TRPV1 that are localized in the putative pore-loop region; and activation of TRPV1 by CFA1 is not exclusive in mouse lungs but represents a pathway by which CFA1 affects the expression of selected genes in lung epithelial cells and airway tissue.
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It is of urgent need to identify the exact physico-chemical characteristics which allow maximum uptake and accumulation in secondary target organs of nanoparticulate drug delivery systems after oral ingestion. We administered radiolabelled gold nanoparticles in different sizes (1.4-200 nm) with negative surface charge and 2.8 nm nanoparticles with opposite surface charges by intra-oesophageal instillation into healthy adult female rats. The quantitative amount of the particles in organs, tissues and excrements was measured after 24 h by gamma-spectroscopy. The highest accumulation in secondary organs was mostly found for 1.4 nm particles; the negatively charged particles were accumulated mostly more than positively charged particles. Importantly, 18 nm particles show a higher accumulation in brain and heart compared to other sized particles. No general rule accumulation can be made so far. Therefore, specialized drug delivery systems via the oral route have to be individually designed, depending on the respective target organ.
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Silver nanoparticles (Ag-nps) are used as a natural biocide to prevent undesired bacterial growth in clothing and cosmetics. The objective of this study was to assess the antibacterial efficacy of Ag-nps of different sizes, surface conditions, and synthesis methods against Escherichia coli, Ag-resistant E. coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Salmonella sp. Ag-nps samples were synthesized by: Base reduction with unmodified surfaces and used as synthesized ('unwashed'; 20, 50 and 80 nm) or after 20 phosphate buffer washes ('washed'; 20, 50 and 80 nm), or synthesized by laser ablation with carbon-stabilized surfaces ('carbon-coated'; 25 and 35 nm). Unwashed Ag-nps were toxic to all bacterial strains at concentrations between 3.0-8.0 μg/ml. The washed Ag-nps and carbon-coated Ag-nps were toxic to all bacterial strains except Ag-resistant E. coli at concentrations between 64.0-1024.0 μg/ml. Ag-resistant E. coli died only when treated with unwashed Ag-nps or its supernatant, both of which contained formaldehyde.
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Although mankind stands to obtain great benefit from nanotechnology, it is important to consider the potential health impacts of nanomaterials (NMs). This consideration has launched the field of nanotoxicology, which is charged with assessing toxicological potential as well as promoting safe design and use of NMs. Although no human ailments have been ascribed to NMs thus far, early experimental studies indicate that NMs could initiate adverse biological responses that can lead to toxicological outcomes. One of the principal mechanisms is the generation of reactive oxygen species and oxidant injury. Because oxidant injury is also a major mechanism by which ambient ultrafine particles can induce adverse health effects, it is useful to consider the lessons learned from studying ambient particles. This review discusses the toxicological potential of NMs by comparing the possible injury mechanisms and adverse health effects of engineered and ambient ultrafine particles.
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Gametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals. Many chemicals have a negative impact on the germline, either by directly affecting the germ cells, or indirectly through their action on the somatic nursing cells. Ultimately, these effects can inhibit fertility, and they may have negative consequences for the development of the offspring. Recently, nanomaterials such as nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots have received enormous national attention in the creation of new types of analytical tools for biotechnology and the life sciences. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health and the environment. Thus, there are limited studies available on toxicity of nanoparticles for risk assessment of nanomaterials. The purpose of this study was to assess the suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity in the male germline in vitro. The effects of different types of nanoparticles on these cells were evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. Our results demonstrate a concentration-dependent toxicity for all types of particles tested, whereas the corresponding soluble salts had no significant effect. Silver nanoparticles were the most toxic while molybdenum trioxide (MoO(3)) nanoparticles were the least toxic. Our results suggest that this cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro.
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Silver nanoparticles (Ag-NPs) are extensively used in different areas including clothing or food industry. In particular, silver has been used in a range of medical settings such as coatings of medical devices due to well-known long-lasting antimicrobial properties. Silver ions exert antimicrobial effects after binding to a variety of microbial molecules such as DNA, cell wall components or membrane proteins. Despite the widespread use of nanosilver there is a serious lack of information on the biological effects of nanosilver on human tissue cells. It was the purpose of this study to analyze the influence of Ag−NPs on biological functions (proliferation, cytokine release and chemotaxis) of human mesenchymal stem cells (hMSCs). Silver nanoparticles were prepared by the polyol process, i.e. by the reduction of silver nitrate with ethylene glycol in the presence of polyvinylpyrrolidone, PVP. Thereby, the silver nanoparticles were colloidally stabilized by the polymer. hMSCs were incubated with or without PVP-functionalized Ag-NPs (diameter about 100 nm, concentrations 50 ng mL−1 −50 μg mL−1) up to 7 days using cell culture conditions. In addition, control experiments with dissolved silver ions (diluted silver acetate) were performed to separate particle and ion effects. Cell viability was determined after calcein-AM/propidium iodine staining. Chemotaxis of hMSC was quantitated after membrane transmigration and subsequent cell staining. Cell proliferation was analyzed using AlamarBlue-assay. Cytokines were determined by ELISA technique and particle agglomeration was analyzed by the Eye Tech-Particle-Analyzer (Ankersmid, Netherlands). A concentration-dependent activation of hMSCs was observed at nanosilver levels of 2.5 μg mL−1, cytotosic cell reactions occurred at Ag-NPs concentrations above 5 μg mL−1. Cell proliferation and the chemotactic response of hMSC decreased in parallel with increasing nanosilver concentrations. In the presence of Ag−NPs/Ag-ions different effects on cytokine release from hMSCs were observed. At high but non-cytotoxic concentrations of Ag-NPs (2.5 μg mL−1) the release of IL-8 was significantly increased, in contrast, the levels of IL-6 and VEGF were decreased compared to the control. The synthesis of IL-11 was not affected in the presence of silver. The agglomeration of Ag-NPs in different biological media increased after prolonged incubation periods (7 days). These data clearly show that Ag-NPs exert cytotoxic effects on hMSCs at high concentrations but also induced cell activation (as analyzed by IL-8 release) at sublethal concentrations of Ag−NPs.
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Triblock copolymers poly(ethylene oxide) (PEO)–poly(propylene oxide) (PPO)–poly(ethylene oxide) (PEO) Pluronic F127 was employed as capping agent for the Ag(0) metallic nanoparticles synthesized by the chemical reduction of silver nitrate, AgNO3, with excess of sodium borohydride, NaBH4. The morphology and the kinetics of Ag(0) nanoparticles were studied by transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), UV–vis absorption and fluorescence probe technique. Spherical polydisperse particles of 12 ± 4 nm mean diameter at varying the Pluronic concentration in the range of 0.13–13 wt.% were reported. Apart from the stabilizing role, the triblock copolymer promoted the agglomeration of individual Ag(0) nanoparticles in small assemblies whose plasmon band features differed from those of the individual nanoparticles. The formation of Ag(0) nanoparticles–F127 complex took place after full reduction of the Ag+ ions and it was controlled by the F127 concentration. The nanoparticle morphology and the fluorescence probe technique suggested that the excess Pluronic drove indirectly the Ag(0) nanoparticles association. Free F127 polymeric micelles encountered above critical micellar concentration (cmc) promoted the partial desorption of the adsorbed triblock copolymer and subsequently weakened the stability of the individual nanoparticles.
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1. Introduction.- 2. Theoretical Considerations.- 3. Experimental Methods.- 4. Experimental Results and Discussion.- A.1 Tables: Optical Spectroscopy Experiments with Metal Clusters.- A.2 Survey of Optical Spectra of Elemental Metal Clusters and Chain-Aggregates.- A.3 Mie Computer Program.- References.
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Although mankind stands to obtain great benefit from nanotechnology, it is important to consider the potential health impacts of nanomaterials (NMs). This consideration has launched the field of nanotoxicology, which is charged with assessing toxicological potential as well as promoting safe design and use of NMs. Although no human ailments have been ascribed to NMs thus far, early experimental studies indicate that NMs could initiate adverse biological responses that can lead to toxicological outcomes. One of the principal mechanisms is the generation of reactive oxygen species and oxidant injury. Because oxidant injury is also a major mechanism by which ambient ultrafine particles can induce adverse health effects, it is useful to consider the lessons learned from studying ambient particles. This review discusses the toxicological potential of NMs by comparing the possible injury mechanisms and adverse health effects of engineered and ambient ultrafine particles.
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Silver colloids in aqueous solution were studied by different scanning microscopy techniques and UV/VIS spectroscopy. The silver colloids were produced either by chemical reduction or by nanosecond laser ablation from a solid silver foil in water. Variation of laser power and ablation time leads to solutions of metal clusters of different sizes in water. We characterized the electronic absorption of the clusters by UV/VIS spectroscopy. STM (scanning tunneling microscope) imaging of the metal colloids shows atomic resolution of rod- or tenon-like silver clusters up to 10-nm length formed by laser ablation. Our scanning electron microscope measurements, however, show that much larger silver colloids up to 5-μm length are also formed, which are not visible in the STM due to their roughness. We correlate them with the long-wavelength tail of the multimodal UV/VIS spectrum. The silver colloids obtained by chemical reduction are generally larger and their electronic spectra are red-shifted compared to the laser-ablated clusters. Irradiation of the colloid solution with nanosecond laser pulses of appropriate fluence at 532nm and 355nm initially reduced the colloid size. Longer irradiation at 355nm, however, leads to the formation of larger colloids again. There seems to be a critical lower particle size, where silver clusters in aqueous solution become unstable and start to coagulate.
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Surface plasmon resonance (SPR) for spherical shaped silver nanoparticles showing double maxima at 390 nm and �520 nm respectively is reported. Self assembly of silver nanoparticles grown on tryptophan template leads to emergence of equal intensity double plasmon resonance (EIDPR). While for rod shaped nano-forms such double plasmon is explainable but for spherical shaped forms, such double plasmon can be explained on the basis of bidirectional formation of silver cluster in which attachment of silver at two nitrogen atom locations of tryptophan molecule seems to be obligatory. The absence of double resonance in case of silver nanoclusters formed with other amino acids or N-acetyl L-tryptophanamide (NATA), where bidirectional –NH2 attachment is not possible, validates the proposed EIDPR mechanism. Electron micrograph of EIDPR particle indicates a bi-periodic fringe pattern indicating unusual crystalline property. Apart from sensing tryptophan, the double plasmon peaks are sensitive to temperature. Furthermore, the particle can be used as a smart killing agent showing bactericidal activity only upon exposure to low power laser.
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As a result of mankind's over-reliance on antibiotics, germs are becoming more drug-resistant every year. The gradual but inexorable decline in the efficacy of traditional antibiotics is forcing scientists and doctors to search for new weapons in the fight against germs. Metallic silver nanoparticle (Ag0) and ionic silver (Ag+) are the future of the post-antibiotic era, with the latter playing perhaps the central role in this fight. Using the arc discharge method (ADM), our research has allowed us to fabricate silver nanoparticle suspension (SNPS) in deionized water with no added surfactants. Most related research in this field is confined to explore the composition of nanoparticle, ignoring ions. However, we aim to identify and measure the proportion of ionic silver in ADM-SNPS, using conductivity meters, centrifuges, titrator, and atomic absorption spectrophotometer (AA). The results of our experiments show that SNPS fabricated by means of ADM with no added surfactants contains metallic silver nanoparticle and ionic silver. The fabrication consumes silver rods at a rate of 100 mg/min, yielding metallic silver nanoparticle and ionic silver with concentrations of approximately 11 ppm and 19 ppm, respectively.
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Primary cells are ideal for in vitro toxicity studies since they closely resemble tissue environment. Here, we report a detailed study on the in vitro interactions of 7–20 nm spherical silver nanoparticles (SNP) with primary fibroblasts and primary liver cells isolated from Swiss albino mice. The intended use of silver nanoparticles is in the form of a topical antimicrobial gel formulation for the treatment of burns and wounds.Upon exposure to SNP for 24 h, morphology of primary fibroblasts and primary liver cells remained unaltered up to 25 μg/mL and 100 μg/mL SNP, respectively, although with minor decrease in confluence. IC50 values for primary fibroblasts and primary liver cells as revealed by XTT assay were 61 μg/mL and 449 μg/mL, respectively. Ultra-thin sections of primary cells exposed to 1/2 IC50 SNP for 24 h, visualized under Transmission electron microscope showed the presence of dark, electron dense, spherical aggregates inside the mitochondria, and cytoplasm, probably representing the intracellular SNP. When the cells were challenged with ∼ 1/2 IC50 concentration of SNP (i.e. 30 μg/mL and 225 μg/mL for primary fibroblasts and primary liver cells, respectively), enhancement of GSH (∼ 1.2 fold) and depletion of lipid peroxidation (∼ 1.4 fold) were seen in primary fibroblasts which probably protect the cells from functional damage. In case of primary liver cells; increased levels of SOD (∼ 1.4 fold) and GSH (∼ 1.1 fold) as compared to unexposed cells were observed. Caspase-3 activity assay indicated that the SNP concentrations required for the onset of apoptosis were found to be much lower (3.12 μg/mL in primary fibroblasts, 12.5 μg/mL in primary liver cells) than the necrotic concentration (100 μg/mL in primary fibroblasts, 500 μg/mL in primary liver cells). These observations were confirmed by CLSM studies by exposure of cells to 1/2 IC50 SNP (resulting in apoptosis) and 2× IC50) cells (resulting in necrosis).These results clearly suggest that although silver nanoparticles seem to enter the eukaryotic cells, cellular antioxidant mechanisms protect the cells from possible oxidative damage. This property, in conjunction with the finding that primary cells possess much higher SNP tolerance than the concentration in the gel (∼ 20 μg/g), indicates preliminary safety of the formulation and warrants further study for possible human application.
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A summary of a critical review by a working group of the German Federal Environment Agency and the German Federal Institute for Risk Assessment on the carcinogenic potential of nanomaterials is presented. After a critical review of the available data, we conclude that the potential carcinogenic risk of nanomaterials can currently be assessed only on a case-by-case basis. There is certain evidence that different forms of CNTs (carbon nanotubes) and nanoscale TiO2 particles may induce tumours in sensitive animal models. It is assumed that the mode of action of the inhalation toxicity of asbestos-like fibres and of inhalable fractions of biopersistent fine dusts of low toxicity (nano-TiO2) is linked to chronic inflammatory processes. Existing epidemiological studies on carcinogenicity for these manufactured nanomaterials are not sufficiently conclusive.
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Despite the wide use of silver nanoparticles (nano Ag), its toxicity still remains poorly understood. In this report, nano Ag induced an increase in platelet aggregation and procoagulant activation which are the key contributors to thrombotic diseases. In freshly isolated human platelets, nano Ag induced platelet aggregation and procoagulant activation evident by increased phosphatidylserine exposure and thrombin generation. Interestingly, the sub-threshold level of thrombin enhanced nano Ag-induced platelet activation significantly indicating that the prothrombotic effects of nano Ag might be further potentiated in activated platelets. An increase in intracellular calcium mediated nano Ag induced platelet activation and P-selectin expression, and serotonin release was also enhanced by nano Ag. Consistent with the in vitro results, exposure to nano Ag (0.05-0.1 mg/kg i.v. or 5-10 mg/kg intratracheal instillation) in vivo enhanced venous thrombus formation, platelet aggregation, and phosphatidylserine externalization ex vivo in rats suggesting that nano Ag, indeed, does enhance thrombus formation through platelet activation.
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Nanotechnology is rapidly growing with nanoparticles produced and utilized in a wide range of commercial products throughout the world. For example, silver nanoparticles (Ag NP) are used in electronics, bio-sensing, clothing, food industry, paints, sunscreens, cosmetics and medical devices. These broad applications, however, increase human exposure and thus the potential risk related to their short- and long-term toxicity. A large number of in vitro studies indicate that Ag NPs are toxic to the mammalian cells derived from skin, liver, lung, brain, vascular system and reproductive organs. Interestingly, some studies have shown that this particle has the potential to induce genes associated with cell cycle progression, DNA damage and apoptosis in human cells at non-cytotoxic doses. Furthermore, in vivo bio-distribution and toxicity studies in rats and mice have demonstrated that Ag NP administered by inhalation, ingestion or intra-peritoneal injection were subsequently detected in blood and caused toxicity in several organs including brain. Moreover, Ag NP exerted developmental and structural malformations in non-mammalian model organisms typically used to elucidate human disease and developmental abnormalities. The mechanisms for Ag NP induced toxicity include the effects of this particle on cell membranes, mitochondria and genetic material. This paper summarizes and critically assesses the current studies focusing on adverse effects of Ag NPs on human health.
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Nanotechnology, nanomedicine and nanotoxicology are complementary disciplines aimed at the betterment of human life. However, concerns have been expressed about risks posed by engineered nanomaterials (ENMs), their potential to cause undesirable effects, contaminate the environment and adversely affect susceptible parts of the population. Information about toxicity and biokinetics of nano-enabled products combined with the knowledge of unintentional human and environmental exposure or intentional delivery for medicinal purposes will be necessary to determine real or perceived risks of nanomaterials. Yet, results of toxicological studies using only extraordinarily high experimental doses have to be interpreted with caution. Key concepts of nanotoxicology are addressed, including significance of dose, dose rate, and biokinetics, which are exemplified by specific findings of ENM toxicity, and by discussing the importance of detailed physico-chemical characterization of nanoparticles, specifically surface properties. Thorough evaluation of desirable versus adverse effects is required for safe applications of ENMs, and major challenges lie ahead to answer key questions of nanotoxicology. Foremost are assessment of human and environmental exposure, and biokinetics or pharmacokinetics, identification of potential hazards, and biopersistence in cells and subcellular structures to perform meaningful risk assessments. A specific example of multiwalled carbon nanotubes (MWCNT) illustrates the difficulty of extrapolating toxicological results. MWCNT were found to cause asbestos-like effects of the mesothelium following intracavitary injection of high doses in rodents. The important question of whether inhaled MWCNT will translocate to sensitive mesothelial sites has not been answered yet. Even without being able to perform a quantitative risk assessment for ENMs, due to the lack of sufficient data on exposure, biokinetics and organ toxicity, until we know better it should be made mandatory to prevent exposure by appropriate precautionary measures/regulations and practicing best industrial hygiene to avoid future horror scenarios from environmental or occupational exposures. Similarly, safety assessment for medical applications as key contribution of nanotoxicology to nanomedicine relies heavily on nano-specific toxicological concepts and findings and on a multidisciplinary collaborative approach involving material scientists, physicians and toxicologists.