Toxicity of silver nanoparticles released by Hancornia speciosa (Mangabeira) biomembrane.

Recent research has shown that latex from different species is able to produce tissue replacement and regeneration. Particularly, biomembranes obtained from Hancornia speciosa latex (HSB) have shown high angiogenic and osteogenic activity. Considering new materials for wound healing, it would be interesting to develop a product combining antibacterial and antifungal activities. Silver nanoparticles (AgNP) have been commonly used for this purpose in medicinal products and devices for decades. In order to combine angiogenic, antibacterial and antifungal properties on the same platform, we developed an HSB containing 3 concentrations of AgNP. It was observed that the HSB successfully accommodated the AgNP in the matrix and released them in a controlled way. The release dynamics of AgNP by HSB was described by UV-vis absorption spectroscopy. The released nanoparticles were evaluated by Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) measurements. In addition, the cytotoxic and genotoxic effects were evaluated using the Allium cepa assay. The results showed no cytotoxic effect of HSB-AgNP in all studied concentrations. The genotoxic effect was observed in HSB-AgNP at the two highest concentrations, however not at the lowest concentration. Thus, the addition of AgNP at the lowest concentration can improve the pharmacological activity of HSB without causing a toxic effect on vegetal cells. Therefore, the H. speciosa latex biomembrane presented in this paper combines angiogenic, anti-inflammatory and antibacterial properties and can be considered potentially new biomaterial for wound-healing.

Polydopamine-coated Au-Ag nanoparticle-guided photothermal colorectal cancer therapy through multiple cell death pathways.

Nanoparticles are emerging as a new therapeutic modality due to their high stability, precise targeting, and high biocompatibility. Branched Au-Ag nanoparticles with polydopamine coating (Au-Ag@PDA) have strong near-infrared absorbance and no cytotoxicity but high photothermal conversion efficiency. However, the photothermal activity of Au-Ag@PDA in vivo and in vitro has not been reported yet, and the mechanism underlying the effects of photothermal nanomaterials is not clear. Therefore, in this study, the colorectal cancer cell line HCT-116 and nude mice xenografts were used to observe the photothermal effects of Au-Ag@PDA in vivo and in vitro. The results suggest that Au-Ag@PDA NPs significantly inhibited cell proliferation and induced apoptosis in colorectal cancer cells. Moreover, Au-Ag@PDA NP-mediated photothermal therapy inhibited the growth of tumors at doses of 50 and 100 µg in vivo. The mechanisms through which Au-Ag@PDA NPs induced colorectal cancer cell death involved multiple pathways, including caspase-dependent and -independent apoptosis, mitochondrial damage, lysosomal membrane permeability, and autophagy. Thus, our findings suggest that Au-Ag@PDA NPs could be used as potential antitumor agents for photothermal ablation of colorectal cancer cells.

Antioxidant and anticancer activities of green synthesized silver nanoparticles using aqueous extract of tubers of Pueraria tuberosa.

In the present study, we have synthesized silver nanoparticles (AgNPs) using Pueraria tuberosa aqueous extract (PTAE) in a straightforward manner without involvement of toxic chemicals. Various reaction parameters (reaction time, AgNO3 concentration, pH, reaction temperature and PTAE concentration) were optimizeded for the synthesis of AgNPs through visual observation of colour change and absorption peak by UV-Vis spectroscopy. The green synthesized AgNPs were analyzed by DLS, FTIR, SEM, TEM, EDS and XRD for their bio-physical characteristics. The AgNPs were screened for their antioxidant activity by determining total antioxidant capacity (TAC) and anticancer potential by MTT assay. The average particle size of AgNPs was 162.72 ± 5.02 nm with zeta potential of -30.14 ± 2.08 mV. The spherical shape of the AgNPs was confirmed by SEM and TEM. FTIR spectra showed the involvement of different phytoconstituents as capping and stabilizing agents in the synthesis of AgNPs. The TAC of the optimized synthesized AgNPs was more than PTAE. The IC50 of synthesized AgNPs against MCF-7, MDA-MB-231, SKOV-3, U-87 and NCI/ADR cell lines was 3.859, 1.128, 29.36, 6.053 and 25.49 µg/ml, respectively. The green synthesized AgNPs has potential for use in the treatment of different types of cancer.

Green synthesized silver nanoparticles: Catalytic dye degradation, in vitro anticancer activity and in vivo toxicity in rats.

In this study, silver nanoparticles were synthesized (AgNPs) using aqueous rhizome extract of Acorus calamus (ACRE) and evaluated their in vitro anticancer activity and in vivo toxicity in a Wistar rat model. The synthesized AgNPs showed good catalytic activity against different organic pollutant dyes. In vitro cytotoxic effects of AgNPs were assessed in Hep2, COLO 205 and SH-SY5Y cells using MTT assay. Further, the apoptotic changes induced by AgNPs in more susceptible Hep2 cells were observed through AO/EB, DCFH-DA, Rhodamine 123, PI/DAPI staining, oxidative stress markers and Western blotting. In vivo toxicity study revealed substantial alterations in the levels of serum biochemical markers including AST, ALT, LDH and inflammatory markers such as TNF-α and IL-6 on day 29 when rats treated with AgNPs as compared to control, however, these levels were restored to normal at the end of washout period on day 89. No remarkable changes were observed in liver oxidative stress enzymes. ICP-OES analysis indicated bio-distribution of silver in spleen (5.67 µg/g) and liver (4.98 µg/g) in rats treated with 10 mg/kg b.w of AgNPs on day 29 and elimination of silver from all organs was observed at the end of washout period on day 89. Histopathological analysis revealed no significant changes in kidney, spleen, lungs, heart, testis and brain with 5 and 10 mg/kg b.w of AgNP. However, 10 mg/kg b.w of AgNPs showed moderate degree of cell swelling and vacuolar degeneration in liver and these alterations were reverted back to normal at the end of washout period. Findings from this study signify green synthesized AgNPs at low concentrations might be useful in many ways with ecofriendly nature.

Pharmaceutical aspects of silver nanoparticles.

Silver nanoparticles are particles in the size ranging between 1 and 100 nm. The two major methods used for synthesis of silver nanoparticle are the physical and chemical methods with the disadvantage that they are expensive and can also have toxicity. Biological method is being used as an expedient alternative, as this approach is environment-friendly and less toxic and it includes plant extracts, microorganism, fungi, etc. The major applications of silver nanoparticles in the medical field include diagnostic applications and therapeutic applications, apart from its antimicrobial activity. Due to their nanotoxicity, AgNPs have a several drawbacks too. This review presents a complete view of the mechanism of action, synthesis, the pharmacokinetics of silver nanoparticles, different formulations of AgNPs used in biomedical applications, infertility management, antibacterial effects, skin damage, burns, cancer treatment, etc. and various applications of silver nanoparticles together with the possible toxicological challenge.

Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis.

INTRODUCTION: Osteomyelitis, a common and debilitating invasive infection of bone, is a frequent complication following orthopedic surgery and causes pathologic destruction of skeletal tissues. Bone destruction during osteomyelitis results in necrotic tissue, which is poorly penetrated by antibiotics and can serve as a nidus for relapsing infection. Osteomyelitis therefore frequently necessitates surgical debridement procedures, which provide a unique opportunity for targeted delivery of antimicrobial and adjunctive therapies. Areas covered: Following surgical debridement, tissue voids require implanted materials to facilitate the healing process. Antibiotic-loaded, non-biodegradable implants have been the standard of care. However, a new generation of biodegradable, osteoconductive materials are being developed. Additionally, in the face of widespread antimicrobial resistance, alternative therapies to traditional antibiotic regimens are being investigated, including bone targeting compounds, antimicrobial surface modifications of orthopedic implants, and anti-virulence strategies. Expert commentary: Recent advances in biodegradable drug delivery scaffolds make this technology an attractive alternative to traditional techniques for orthopedic infection that require secondary operations for removal. Advances in novel treatment methods are expanding the arsenal of viable antimicrobial treatment strategies in the face of widespread drug resistance. Despite a need for large scale clinical investigations, these strategies offer hope for future treatment of this difficult invasive disease.

Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model.

Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity.

In Vivo toxicological assessment of biologically synthesized silver nanoparticles in adult Zebrafish (Danio rerio).

The present study examines the deleterious effect of biologically synthesized silver nanoparticles in adult zebrafish. Silver nanoparticles (AgNPs) used in the study were synthesized by treating AgNO3 with aqueous leaves extract of Malva crispa Linn., a medicinal herb as source of reductants. LC50 concentration of AgNPs at 96 h was observed as 142.2 µg/l. In order to explore the underlying toxicity mechanisms of AgNPs, half of the LC50 concentration (71.1 µg/l) was exposed to adult zebrafish for 14 days. Cytological changes and intrahepatic localization of AgNPs were observed in gills and liver tissues respectively, and the results concluded a possible sign for oxidative stress. In addition to oxidative stress the genotoxic effect was observed in peripheral blood cells like presence of micronuclei, nuclear abnormalities and also loss in cell contact with irregular shape was observed in liver parenchyma cells. Hence to confirm the oxidative stress and genotoxic effects the mRNA expression of stress related (MTF-1, HSP70) and immune response related (TLR4, NFKB, IL1B, CEBP, TRF, TLR22) genes were analyzed in liver tissues and the results clearly concluded that the plant extract mediated synthesis of AgNPs leads to oxidative stress and immunotoxicity in adult zebrafish.

Design and construction of a silver(I)-loaded cellulose-based wound dressing: trackable and sustained release of silver for controlled therapeutic delivery to wound sites.

Although application of silver nitrate and silver sulfadiazine have been shown to be effective in thwarting infections at burn sites, optimization of the delivery of bioactive silver (Ag(+)) remains as an obstacle due to rapid precipitation and/or insolubility of the silver sources. To circumvent these shortcomings, we have designed a silver(I) complex [Ag(ImD)2]ClO4 (ImD = dansyl imidazole) that effectively increases the bioavailability of Ag(+) and exhibits MIC values of 2.3 and 4.7 µg/mL against E. coli and S. aureus, respectively. This fluorescent silver complex has been incorporated within a robust hydrogel derived from carboxymethyl cellulose that allows slow release of silver. A complete occlusive dressing has finally been constructed with the Ag(ImD)CMC (1% Ag loaded) pad sealed between a sterile mesh gauze (as bottom layer) and a rayon-based surgical tape (as the top layer). Such construction has afforded a dressing that displays sustained delivery of silver onto a skin and soft tissue infection model and causes effective eradication of bacterial loads within 24 h. The transfer of the bioactive silver complex is readily visualized by the observed fluorescence that overlays precisely with the kill zone. The latter feature introduces a unique feature of therapeutic trackability to this silver-donating occlusive dressing.

Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics.

In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma (BM) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future.

Sustained broad-spectrum antibacterial effects of nanoliposomes loaded with silver nanoparticles.

BACKGROUND: The emergence of microbial resistance to antibiotics warrants the search for effective broad-spectrum antibacterial agents. Silver nanoparticles (AgNPs) have been used as antimicrobial agents. AgNPs encapsulated in nanolipososmes have been developed as effective antimicrobial agents. MATERIALS & METHODS: Nanoliposomes (<50 nm) were prepared using a modified reverse-phase evaporation method, and spherical, dextrose-capped AgNPs were synthesized. The prepared liposome AgNPs (LAgNPs) were characterized, and tested for their antibacterial effects. RESULTS: The size of LAgNPs is 25-80 nm. The release of AgNPs from nanoliposomes was sustained over 10 h. Complete growth inhibition of Eschericia coli, Salmonella enterica, Pseudomonas aeruginosa and Staphylococcus aureus was achieved using 180, 200, 160 and 120 µM, respectively, of LAgNPs. LAgNPs exhibited sustained broad-spectrum antibacterial effects compared with free AgNPs. CONCLUSION: Nanoliposomes loaded with AgNPs are potentially effective broad-spectrum antimicrobial agents. This new formula, which can be further fortified by encapsulation of additional established antibacterial agents, may be effective against antibiotic-resistant bacteria and also promote wound healing.

Subchronic oral toxicity of silver nanoparticles.

BACKGROUND: The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems. RESULTS: This study tested the oral toxicity of silver nanoparticles (56 nm) over a period of 13 weeks (90 days) in F344 rats following Organization for Economic Cooperation and Development (OECD) test guideline 408 and Good Laboratory Practices (GLP). Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose (30 mg/kg), middle-dose (125 mg/kg), and high-dose (500 mg/kg). After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P < 0.05) in the body weight of male rats after 4 weeks of exposure, although there were no significant changes in food or water consumption during the study period. Significant dose-dependent changes were found in alkaline phosphatase and cholesterol for the male and female rats, indicating that exposure to more than 125 mg/kg of silver nanoparticles may result in slight liver damage. Histopathologic examination revealed a higher incidence of bile-duct hyperplasia, with or without necrosis, fibrosis, and/or pigmentation, in treated animals. There was also a dose-dependent accumulation of silver in all tissues examined. A gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in female kidneys compared to male kidneys. CONCLUSIONS: The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level) of 30 mg/kg and LOAEL (lowest observable adverse effect level) of 125 mg/kg are suggested from the present study.

Subchronic inhalation toxicity of silver nanoparticles.

The subchronic inhalation toxicity of silver nanoparticles was studied in Sprague-Dawley rats. Eight-week-old rats, weighing approximately 253.2 g (males) and 162.6 g (females), were divided into four groups (10 rats in each group): fresh-air control, low dose (0.6 x 10(6) particle/cm(3), 49 microg/m(3)), middle dose (1.4 x 10(6) particle/cm(3), 133 microg/m(3)), and high dose (3.0 x 10(6) particle/cm(3), 515 microg/m(3)). The animals were exposed to silver nanoparticles (average diameter 18-19 nm) for 6 h/day, 5 days/week, for 13 weeks in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and pulmonary function tests were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and the organ weights were measured. Bile-duct hyperplasia in the liver increased dose dependently in both the male and female rats. Histopathological examinations indicated dose-dependent increases in lesions related to silver nanoparticle exposure, including mixed inflammatory cell infiltrate, chronic alveolar inflammation, and small granulomatous lesions. Target organs for silver nanoparticles were considered to be the lungs and liver in the male and female rats. No observable adverse effect level of 100 microg/m(3) is suggested from the experiments.

Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats.

The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, and home products. However, while the population exposed to silver nanoparticles continues to increase with ever new applications, silver nanoparticles remain a controversial research area as regards their toxicity to biological systems. In particular, the oral toxicity of silver nanoparticles is of particular concern to ensure public and consumer health. Accordingly, this study tested the oral toxicity of silver nanoparticles (60 nm) over a period of 28 days in Sprague-Dawley rats following Organization for Economic Cooperation and Development (OECD) test guideline 407 with Good Laboratory Practice (GLP) application. Eight-week-old rats, weighing about 283 g for the males and 192 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose group (30 mg/kg), middle-dose group (300 mg/kg), and high-dose group (1000 mg/kg). After 28 days of exposure, the blood biochemistry and hematology were investigated, along with a histopathological examination and silver distribution study. The male and female rats did not show any significant changes in body weight relative to the doses of silver nanoparticles during the 28-day experiment. However, some significant dose-dependent changes were found in the alkaline phsophatase and cholesterol values in either the male or female rats, seeming to indicate that exposure to over more than 300 mg of silver nanoparticles may result in slight liver damage. There were no statistically significant differences in the micronucleated polychromatic erythrocytes (MN PCEs) or ratio of polychromatic erythrocytes among the total erythrocytes after silver nanoparticle exposure when compared with the control. Therefore, the present results suggest that silver nanoparticles do not induce genetic toxicity in male and female rat bone marrow in vivo. Nonetheless, the tissue distribution of silver nanopaticles did show a dose-dependent accumulation of silver content in all the tissues examined. In particular, a gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in the female kidneys when compared with the male kidneys.

[How I treat... the critical bacterial colonization of a leg ulcer. The Yin and the Yang features of silver-based dressings]. / Comment je traite.... la colonisation bactérienne critique d'un ulcère de jambe. Le Yin et le Yang des pansements argentiques.

The critical bacterial colonizaion of leg ulcers can impair their healing rate, aggravate the patient discomfort and increase the medical and nursing costs. In recent times, the dressings designed for leg ulcers have followed a pace of conceptual revolution. Some of them are now offered containing an antiseptic of the silver salt family. The silver concentraton delivered into the wound bed is important to consider when assessing treatment efficacy. The diversity of the silver-based dressings currently on the European market is as large as their differences in activity. Only a minority of these dressings adequately control the wound biocenosis. Their cost which is high for the patient, must be compared to that of nursing care that may become less important. The expected beneficit is a reduction in healing time.

Growth conditions, elemental accumulation and induced physiological changes in Chinese cabbage.

Soils contaminated with low levels of heavy metals and other trace elements are now frequently used for vegetable growing. In this situation, heavy metals and trace elements from these polluted soils may accumulate in the agricultural plants being grown in them and thereby enter the human food chain. The objectives of this study are to elucidate the effects of growth conditions, manipulated by the crop covers, on the phytoaccumulation of elements, and to investigate the conceivable influences of these conditions on the plant biochemistry. In three consecutive years of field experiments, open air (T(0)), and floating rowcover treatments (T(1): perforated polyethylene 50 micrometers; T(2): polypropylene 17 gm(-2)) were used to produce different environmental conditions for the growth of Chinese cabbage [Brassica rapa L. (Pekinensis group) cv. 'Nagaoka 50']. Five samplings (whole tops) were carried out from transplanting to harvest and measurements of B, Al, Ag, Si and Ca concentration as well as phenolics (orto-diphenols, total phenols and anthocyanins), pectic fractions, amino acids (histidine, phenylalanine and tyrosine) and polyphenol oxidase activity, were carried out in samples. The T(1) (perforated polyethylene sheet) gave greater B, Al, Ag and Si concentration and phytoextraction (in weight units) than the open-air control. These findings can help to develop new cost-effective techniques for phytoremediation as the application of plastic covers in the field. The build-up of heavy metals in those crops would make the product less suitable for human consumption.

A method to increase silver biosorption by an industrial strain of Saccharomyces cerevisiae.

Ag+ biosorption by an industrial strain of Saccharomyces cerevisiae was investigated. Older (96 h old) biomass had half the biosorption capacity of younger (24 h old) biomass (0.187 and 0.387 mmol Ag+/g dry mass respectively). Comparisons of cell walls isolated from biomass of either age indicated that chemical composition and Ag+ biosorption capacity varied little over the time span examined and that cell walls from either age of culture had small Ag+ biosorption capacities compared to whole cells of a similar age. Silver-containing precipitates were observed both on the cell wall and within the cell, indicating that intracellular components sorbed Ag+. The concentration of these precipitates within the cell appeared visually to decrease with age in Ag(+)-exposed cells. Incorporation of L-cysteine into the growth medium resulted in biomass with increased silver biosorption capacities, protein and sulphydryl group content. Increasing the concentration of L-cysteine in the growth medium from 0 to 5.0 mM increased silver biosorption from 0.389 to 0.556 mmol Ag+/g dry mass. Isolated cell walls of biomass grown in supplemented media also showed a possible link between silver biosorption capacities, protein and sulphydryl group content. No precipitates were observed in silver-exposed biomass that had been grown in the presence of 5.0 mM L-cysteine.

Autometallographic detection of silver in hypothalamic neurons of rats exposed to silver nitrate.

The silver amplification technique, autometallography, has been used to reveal silver accumulation in neurons in the hypothalamus of male Wistar-Kyoto rats. Silver penetrated the blood-brain barrier after exposure to silver nitrate, and differences in staining intensity were found between the hypothalamic nuclei. When using light microscopy, the silver staining of the hypothalamic neurons was highly heterogeneous. Silver was detected exclusively in lysosomes of the loaded neurons. Aspects of this heterogeneous localization are discussed in relation to the distribution of autometallographically developed gold and mercury.