A Review on Synthesis, Antimicrobial Effects and

Sanjay Kumar Rout et. al. / International Journal of Modern Sciences and Engineering Technology (IJMSET)ISSN 2349-3755; Available at https://www.ijmset.com

Volume 2, Issue 11, 2015, pp.6-21

© IJMSET-Advanced Scientific Research Forum (ASRF), All Rights Reserved“IJMSET promotes research nature, Research nature enriches the world’s future”

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A Review on Synthesis, Antimicrobial Effects and Toxicologyconsiderations of Silver Nano Particles

AbstractNanoparticles of noble metals such as silver exhibited significantly distinct physical, chemical and biological

properties from their bulk counterparts. Silver-Nanoparticles (Ag-NPs) can exhibit superior properties thanthose of bulk material due to Nano-size particles of less than 100 nm in diameter, high surface area, quantumconfinement and other effects. Now-a-days the infectious diseases have been a significant impact on moderncivilization and global economics. The treatments of environments containing these infectious pathogens usingdisinfectant nanomaterials have been proposed for the prevention of the outbreaks. Ag-NPs with uniqueproperties of high antimicrobial properties have attracted much interest to develop Nano silver-baseddisinfectant products. This review focuses on effective and efficient synthesis routes along with antimicrobialeffects of Ag-NPs against various pathogens including bacteria, fungi and virus. Finally, toxicologyconsiderations of Ag-NPs to human and ecology are discussed in detail.

Keywords: silver nanoparticles; bacteria; antimicrobial effects; fungi; toxicology and virus.

1.INTRODUCTION:Nanotechnology is an emerging scientific field considered to have potential to generate unique andinnovative materials. It can be defined as a whole knowledge on fundamental properties of Nano-sizeobjects [1-3]. Technically nanoparticles are clusters of atoms in the size range of 1–100 nm [4].Nanotechnology provides the ability to open new avenues to prevent and treat diseases by tailoringmaterials on an atomic scale [5]. Nanomaterials may provide solutions to technological andenvironmental challenges in the areas of renewable energies, environmental remediation, biomedicaldevices, catalysis, cosmetics and water treatment [6-9]. Among them, silver nanoparticles (Ag-NPs)have attracted increasing interest due to their unique physical, chemical and biological propertiescompared to their macro-scaled counterparts [10]. Ag-NPs have distinctive physico-chemicalproperties, high electrical and thermal conductivity, surface-enhanced Raman scattering, chemicalstability, catalytic activity and nonlinear optical behavior [11]. These properties make them ofpotential value inks, micro electronics and medical imaging [12]. It is a well-known fact that silverions and silver-based compounds are highly toxic to microorganisms which include16 major speciesof bacteria [13, 14]. This aspect of silver makes it an excellent choice for multiple roles in the medicalfield. Silver is generally used in the nitrate form to induce antimicrobial effect, but when silvernanoparticles are used, there is a huge increase in the surface area available for the microbe to beexposed to. It has been hypothesized that silver nanoparticles can cause cell lysis or inhibit cell

Krushna Gopal Mishra5

Department of Chemistry,School of Applied Sciences,

KIIT University,Bhubaneswar,

Email:[email protected]

Bankim Chandra Tripathy 4

Principal Scientist (CSIR),Faculty of Chemical Sciences (AcSIR),

Hydro & Electrometallurgy Department,Institute of Minerals and Materials Technology,

Bhubaneswar.Email:[email protected]

#Sanjay Kumar Rout1

Department of Chemistry,Konark Institute of Science &

Technology, Odisha,Bhubaneswar, India.


Bikash Ranjan Kar2

Department ofDermatology,

IMS and Sum Hospital,Bhubaneswar, India.


Payodhar Padhi3

Research and Development Center,Hi-Tech Medical College &

Hospital,Bhubaneswar, India.


mailto:kgmishrafch:@kiit.ac.in


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transduction. There are various mechanisms involved in cell lysis and growth inhibition so Ag-NPsexhibit broad spectrum bactericidal and fungicidal activity [15] that has made them extremely popularin a diverse range of consumer products, including plastics, soaps, pastes, food, textiles and increasingtheir market value [16–18]. Ag-NPs are receiving increasing attention in biomedical applications suchas biological sensing, antimicrobial ointments, medical diagnostics, cancer therapy, drug delivery andartificial implants [19-21]. Ag-NPs can also be utilized either in the textile industry by incorporating itinto the fiber (spun) or employed in filtration membranes of water purification systems. In many ofthese applications, the technological idea is to store silver ions and incorporate a time-releasemechanism. This usually involves some form of moisture layer that the silver ions are transportedthrough to create a long-term protective barrier against bacterial/fungal pathogens [16-18]. Silver ionsare used in the formulation of dental resin composites; in coatings of medical devices; as abactericidal coating in water filters; as an antimicrobial agent in air sanitizer sprays, pillows,respirators, socks, wet wipes, detergents, shampoos, washing machines, and many other consumerproducts; as bone cement; and in many wound dressings to name a few. It is emphasized that a largenumber of practical applications utilizing Ag-NPs in consumer products are being developed inparallel with study of these syntheses and properties.

In recent years a growing number of outbreaks of infectious diseases have emerged. Theseinfectious diseases have occurred in developing and developed countries. Waterborne pathogens andFood are the main factors for the outbreak of these diseases, the transmission of these pathogensendangering public health. The outbreaks of these infectious diseases are a significant burden onglobal economies and public health [22]. To prevent further spread of the infectious pathogens,disinfection methods should be done properly to eliminate these pathogens from infectedenvironmental areas. Particularly, Ag-NPs are drawing increasing attention for potential prevention ofbacterial/fungal and viral infections due to their antimicrobial and disinfectant properties. Thegeneration of efficient and stable Ag-NPs forms offers an advanced perspective in the field ofenvironmental hygiene and sterilization. Though there are various benefits of silver nanoparticles,there is also the problem of Nano toxicity of silver. There are various literatures that suggest that thenanoparticles can cause various environmental and health problems; though there is a need for morestudies to be conducted to conclude that there is a real problem with silver nanoparticles.

This paper aims to review the synthesis routes for production and various techniques forsynthesis of Ag-NPs, the antimicrobial properties of Ag-NPs against fungus, bacteria, virus andpotential mechanisms for antimicrobial activity of Ag-NPs followed by toxicological considerationsof the different Ag-NPs to human health and ecology are discussed in detail.2. SYNTHESIS OF SILVER NANOPARTICLES

Currently, many methods have been reported for the synthesis of Ag-NPs by usingphysical, chemical, photochemical and biological routes. Each method has advantages anddisadvantages with common problems being costs, scalability, particle sizes and size distribution.2.1. Physical synthesis

The physical synthesis process of Ag-NPs generally utilizes the physical energies (thermal,ac power, arc discharge) to produce Ag-NPs with nearly narrow size distribution, which can permitproducing large quantities of Ag-NPs samples in a single process. In this approach the metallic NPscan be generally synthesized by evaporation–condensation, which could be carried out by using a tubefurnace at atmospheric pressure. However, in the case of using a tube furnace at atmospheric pressurethere are several drawbacks such as a large space of tube furnace, great consumption energy forraising the environmental temperature around the source material and a lot of time for achievingthermal stability. Therefore, various methods of synthesis of Ag-NPs based on the physical approachhave been developed. Siegel et al. [23] reported on the development of an unconventional approachfor the physical synthesis of Ag-NPs. The notable metallic NPs were synthesized by direct metalsputtering into the liquid medium. The method, combining physical deposition of metal into propane-1, 2, 3-triol (glycerol), provides an interesting alternative to time-consuming, wet-based chemicalsynthesis techniques. From this method Ag-NPs possess round shape with average diameter of about3.5 nm with standard deviation of 2.4 nm. It was observed that the NPs size distribution and uniformparticle dispersion remains unchanged for diluted aqueous solutions up to glycerol-to-water ratio 1 :20.


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A thermal-decomposition method was developed to synthesize Ag-NPs in powder form[24]. The Ag-NPs were formed by decomposition of an Ag1+–oleate complex, which was prepared bya reaction of AgNO3 and sodium oleate in water solution, at high temperature of 290°C. Averageparticle size of the Ag-NPs was obtained of about 9.5 nm with a standard deviation of 0.7 nmindicating the Ag-NPs have a very narrow size distribution. In another work Jung et al. [25] reportedan attempt to synthesize metal NPs via a small ceramic heater that has a local heating area. The smallceramic heater was used to evaporate source materials. The results showed that the geometric meandiameter, the geometric standard deviation and the total number concentration of NPs increases withheater surface temperature. The particle generation was very stable, because the temperature of theheater surface does not fluctuate with time. Spherical NPs without agglomeration were observed, evenat high concentration with high heater surface temperature. The generated Ag-NPs were pure silver,when air was used as a carrier gas. The geometric mean diameter and the geometric standarddeviation of Ag-NPs were in the range of 6.2–1.5 nm and 1.23-1.88 nm, respectively. Ag-NPs havebeen synthesized with laser ablation of metallic bulk materials in solution by many workers [26-29].The characteristics of the metal particles formed and the ablation efficiency strongly depend uponmany parameters such as the wavelength of the laser impinging the metallic target, the duration of thelaser pulses (in the femto-, Pico- and nanosecond regime), the laser fluence, the ablation time durationand the effective liquid medium, with or without the presence of surfactants [30-33]. The laser fluenceis one of the most important parameters. Indeed, the ejection of metal particles from the targetrequires a minimum power (or fluence). The mean size of the nanoparticles has been found generallyto increase with increasing laser fluence and is generally smallest for fluencies not too far above thelaser breakdown threshold. Besides the laser fluence, the number of laser shots (i.e. the time spentduring laser vaporization) influences the concentration and the morphology of metal particles releasedin a liquid. For longer times under the laser beam the metal particle concentration is expected toincrease, but it can saturate due to light absorption in the colloid highly concentrated in metalparticles.

Mafune et al. [34] reported the formation of nanoparticles by laser ablation is terminated bythe surfactant coating; the nanoparticles formed in a solution of high surfactant concentration aresmaller than those formed in a solution of low surfactant concentration.Tien et al. [35] used the arc discharge method to fabricate Ag-NPs suspension in deionized waterwithout surfactants. In this synthesis, silver wires (Gredmann, 99.99%, 1mm in diameter) weresubmerged in deionized water and used as electrodes. The experimental results show that Ag-NPssuspension fabricated by means of arc discharge method with no added surfactants contains metallicAg-NPs and ionic silver. With a silver rod consumption rate of 100 mg min−1, yielding metallic Ag-NPs of 10 nm in size and ionic silver obtained at concentrations of approximately11 ppm and 19 ppm,respectively. In summary, this is also the most useful method to produce Ag-NPs powder. However,primary costs for investment of equipment should be considered.

2.2. Chemical synthesisAmong the existing methods, the chemical methods have been mostly used for production

of Ag-NPs. Chemical methods provide an easy way to synthesize Ag-NPs in solution. Generally, thechemical synthesis process of the Ag-NPs in solution usually employs the following maincomponents: (i) metal precursors, (ii) reducing agents and (iii) stabilizing /capping agents. Chemicalreduction is the most frequently applied method for the preparation of AgNPs as stable, colloidaldispersions in water or organic solvents. Commonly used reductants are borohydride, citrate,ascorbate and elemental hydrogen. The reduction of silver ions (Ag+) in aqueous solution generallyyields colloidal silver with particle diameters of several nanometers. Initially, the reduction of variouscomplexes with Ag+ ions leads to the formation of silver atoms (Ag°), which is followed byagglomeration into oligomeric clusters. These clusters eventually lead to the formation of colloidal Agparticles [36-39]. The formation of colloidal solutions from the reduction of silver salts involves twostages of nucleation and subsequent growth. It is also revealed that the size and the shape ofsynthesized Ag-NPs are strongly dependent on these stages. Spherical Ag-NPs with a controllablesize and high monodispersity were synthesized by using the polyol process and a modified precursorinjection technique [40]. In the precursor injection method, the injection rate and reaction temperaturewere important factors for producing a reduced and uniform-sized Ag-NPs. Ag-NPs with a size of


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17±2 nm were obtained at an injection rate of 2.5 mls−1 and a reaction temperature of 100°C. Theinjection of the precursor solution into a hot solution is an effective means to induce rapid nucleationin a short period of time, ensuring the fabrication of Ag-NPs with a smaller size and a narrower sizedistribution. Bai et al. [41] explained the most common strategy is to protect the nanoparticles withprotective agents that can be absorbed on or bind onto the nanoparticle surface, avoiding theiragglomeration, so it is important to use protective agents to stabilize dispersive nanoparticles duringthe course of metal nanoparticle preparation.

Monodisperse samples of silver nanocubes were synthesized in large quantities by reducingsilver nitrate with ethylene glycol in the presence of polyvinyl pyrrolidone (PVP) [42], the so-calledpolyol process. In this case, ethylene glycol served as both reductant and solvent. It showed that thepresence of PVP and its molar ratio relative to silver nitrate both played important roles indetermining the geometric shape and size of the product. It suggested that it is possible to tune the sizeof silver nanocubes by controlling the experimental conditions. Nearly monodisperse Ag-NPs havebeen prepared in a simple oleylamine-liquid paraffin system [43]. It was shown that the formationprocess of Ag-NPs could be divided into three stages: growth, incubation and Oatwald ripeningstages. In this method, only three chemicals, including silver nitrate, oleylamine and liquid paraffin,are employed throughout the whole process. The higher boiling point of 300°C of paraffin affords abroader range of reaction temperature and makes it possible to effectively control the size of Ag-NPsby varying the heating temperature alone without changing the solvent. Otherwise, the size of thecolloidal Ag-NPs could be regulated not only by changing the heating temperature or the ripeningtime, but also by adjusting the ratio of oleylamine to the silver precursor. Furthermore, for thesynthesis of mono dispersed Ag-NPs with uniform size distribution, all nuclei are required to form atthe same time. In this case all the nuclei are likely to have the same or similar size and then they willhave the same subsequent growth. The initial nucleation and the subsequent growth of initial nucleican be controlled by adjusting the reaction parameters such as reaction temperature, pH, precursors,reducing agents (i.e.NaBH4, glucose and ethylene glycol ) and stabilizing agents (i.e. sodiumoleate,PVA and PVP) [44-46] considered.

Krutyakov et al. [47] prepared AgNPs inside micro emulsion and reported the synthesis ofAgNPs in two-phase aqueous organic systems is based on the initial spatial separation of reactants(metal precursor and reducing agent) in two immiscible phases. The rate of subsequent interactionbetween the metal precursor and the reducing agent is controlled by the interface between the twoliquids and by the intensity of inter phase transport between the aqueous and organic phases, which ismediated by a quaternary alkyl ammonium salt. Metal clusters formed at the interface are stabilized,due to their surface being coated with stabilizer molecules occurring in the nonpolar aqueous medium,and transferred to the organic medium by the interphase transporter. This method allows preparationof uniform and size controllable nanoparticles. However, it is expensive to fabricate silvernanoparticles by this method, because large amounts of surfactant and organic solvent, which areadded to the system, must be separated and removed from the final product. On other hand, theadvantages of forming particles which are readily dispersed in organic media are recognized byscientific workers in many fields. For instance, colloidal nanoparticles prepared in non aqueous mediafor conductive inks are well-dispersed in a low vapor pressure organic solvent, to readily wet thesurface of polymeric substrate without any aggregation. The advantages can also be found in theapplications of nanometal particles as catalysts to catalyze most organic reactions, which take place innonpolar solvents. It is very important to transfer nanoparticles to different chemicophysicalenvironments in the practical applications. However, the nanoparticles prepared in nonpolar solutionsare infrequent and difficult [48].

2.3. Photochemical synthesisThe NPs are formed by the direct photo reduction of a metal source or reduction of metal

ions using photo-chemically generated intermediates, such as excited molecules and radicals, whichare often called photosensitization in the synthesis of NPs [49, 50]. The main advantages of thephotochemical synthesis are: (i) it provides the advantageous properties of the photo-inducedprocessing, that is, clean process, high spatial resolution, and convenience of use, (ii) the controllablein situ generation of reducing agents; the formation of NPs can be triggered by the photo irradiation


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and (iii) it has great versatility; the photochemical synthesis enables one to fabricate the NPs invarious mediums including emulsion, surfactant micelles, polymer films, glasses, cells etc [50].

The photo-induced synthetic strategies can be categorized into two distinct approaches thatare the photo physical (top down) and photo chemical (bottom up) ones. The former could prepare theNPs via the subdivision of bulk metals and the latter generates the NPs from ionic precursors. UV-initiated photo reduction is a simple and effective method to produce silver nanoparticles in thepresence of citrate, PVP, PAA and collagen. DNA-complexed metal ions can be photo reduced intometal nanoparticle in aqueous media. Huang et al. [51] synthesized AgNPs via photo reduction ofAgNO3 in layered inorganic clay suspensions (laponite) which serves as stabilizing agent that preventnanoparticles from aggregation. The properties of silver nanoparticles were studied as a function ofthe UV irradiation time. A bimodal size distribution and relatively large silver nanoparticles wereobtained when irradiated under UV for 3 h. Further irradiation disintegrated the AgNPs into smallersize with a single mode distribution until a relatively stable size and size distribution were achieved[51]. Pal et al. [52] reported a simple and reproducible UV photo-activation method for thepreparation of stable Ag-NPs in aqueous TritonX-100 (TX-100). The TX-100 molecules play a dualrole: they act as reducing agent and also as NPs stabilizer through template/capping action. Inaddition, surfactant solution helps to carry out the process of NPs growth in the diffusion controlledway (by decreasing the diffusion or mass transfer co–efficient of the system) and also helps toimprove the NPs size distributions (by increasing the surface tension at the solvent–NPs interface). Inanother study, the Ag-NPs were synthesized in an alkaline aqueous solution ofAgNO3/carboxymethylated chitosan (CMCTS) with UV light irradiation. CMCTS, a water-solubleand biocompatible chitosan derivative, served simultaneously as a reducing agent for silver cation anda stabilizing agent for Ag-NPs in this method [53]. It also revealed that the diameter range of as-synthesized Ag-NPs was 2–8 nm and they can be dispersed stably in the alkali CMCTS solution formore than 6 months. The direct photo-reduction process of AgNO3 in the presence of sodium citrate(NaCit) was carried out with different light sources (UV, white, blue, cyan, green and orange) at roomtemperature [54]. It was shown that this light-modification process results in a colloid with distinctiveoptical properties that can be related to the size and shape of the particles.

2.4. Biological synthesisThe biological method provides a wide range of resources for the synthesis of Ag-NPs, and

this method can be considered as an environmentally friendly approach and also as a low costtechnique. The rate of reduction of metal ions using biological agents is found to be much faster andalso at ambient temperature and pressure conditions. Generally, when Ag-NPs are produced bychemical synthesis, three main components are needed: a silver salt, a reducing agent and a stabilizeror capping agent to control the growth of the NPs and prevent them from aggregating. In case of thebiological synthesis of Ag-NPs, the reducing agent and the stabilizer are replaced by moleculesproduced by living organisms. These reducing and/or stabilizing compounds can be utilized frombacteria, fungi, yeasts, algae or plants [55].

Raveendran et al. [56] synthesized starch AgNPs using starch as a capping agent and β-d-glucose as a reducing agent in a gently heated system. The starch in the solution mixture avoids use ofrelatively toxic organic solvents. Additionally, the binding interactions between starch and AgNPs areweak and can be reversible at higher temperatures, allowing separation of the synthesized particles[57]. Vilchis-Nestor et al. [58] used green tea (Camellia sinensis) extract as reducing and stabilizingagent to produce silver nanoparticles in aqueous solution at ambient conditions. Furthermore,Kalishwaralal et al. [59] reported the synthesis of AgNPs by reduction of aqueous Ag+ ions with theculture supernatant of Bacillus licheniformis. The synthesized AgNPs are highly stable and thismethod has advantages over other methods as the organism used here is a nonpathogenic bacterium.A facile biosynthesis using the metal-reducing bacterium, Shewanellaoneidensis, seeded with a silvernitrate solution was reported [60]. The formation of small, spherical, nearly monodispersed Ag-NPs inthe size range from ~2 to 11 nm (average size of 4±1.5 nm) was observed. The Ag-NPs exhibit usefulproperties such as being hydrophilic, stable and having a large surface area. This bacterially basedmethod of synthesis is simple, reproducible, economical, and requires less energy when compared tochemical synthesis processes. Also, the Ag-NPs were produced by using the Lactobcillusspp., asreducing and capping agent. Sintubin et al. [61] were carried with different Lactobcillusspecies to


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accumulate and subsequently reduce Ag+. The result showed that only the lactic acid bacterial wereconfirmed to have the ability to produce Ag°. In addition, both particle localization and distributioninside the cell were dependent on Lactobcillusspecies. The mean diameter of the biogenic Ag-NPsproduced by this method varied with the Lactobacillus spp. used. The smallest NPs were produced byL. fermentum and had a diameter of 11.2 nm; here the recovery of silver and the reduction rate werepH dependent.

The use of the fungus Trichodermaviride (T. viride) for the extracellular biosynthesis ofAg-NPs from silver nitrate solution was reported [62]. In this regard T. viride proves to be animportant biological component for extracellular biosynthesis of stable Ag-NPs. The morphology ofAg-NPs is highly variable, with spherical and occasionally rod-like NPs observed on micrographs.The obtained diameter of Ag-NPs was in the range of from 5 to 40 nm. In another study, stable Ag-NPs of 5–15 nm in size were synthesized by using air borne bacteria (Bacillus sp.) and silver nitrate[63]. The biogenic NPs were observed in the periplasmic space of the bacterial cells, which isbetween the outer and inner cell membranes. On the other hand, Naik et al. [64] have demonstratedthe biosynthesis of biogenic Ag-NPs using peptides selected by their ability to bind to the surface ofsilver particles. By the nature of peptide selection against metal particles, a ‘memory effect’ has beenimparted to the selected peptides. The silver-binding clones were incubated in an aqueous solution of0.1mM silver nitrate for 24–48h at room temperature. The silver particles synthesized by the silver-binding peptides showed the presence of silver particles having 60–150 nm in size.

In biological synthesis, the cell wall of the micro organisms plays a major role in theintracellular synthesis of NPs. The negatively charged cell wall interact electro statically with thepositively charged metal ions and bioreduces the metal ions to NPs [65]. When microorganisms areincubated with silver ions, extracellular Ag-NPs can be generated as an intrinsic defense mechanismagainst the metal’s toxicity. Other green syntheses of Ag-NPs using plant exacts as reducing agentshave been performed [66, 67]. This defense mechanism can be exploited as a method of NPs synthesisand has advantages over conventional chemical routes of synthesis. However, it is not easy to have alarge quantity of Ag-NPs by using biological synthesis.

3. ANTIMICROBIAL EFFECTS OF Ag-NPs3.1. Antibacterial effects

The Ag-NPs are an effective tool for killing disease-causing bacteria. But despite theirwidespread use in catheters, cosmetics, clothing, toys, and many other products [68], investigatorshaven’t fully understood whether their effectiveness is a function of the release of germicidal silverions, some feature specific to their nanoparticle form or both. Xiu et al. [69] reported that the releaseof dissolved silver ions is the driving force behind Ag-NPs germicidal action. Silver ions are powerfulantimicrobials, but they are easily sequestered by chloride, phosphate, proteins, and other cellularcomponents [70]. “Ag-NPs are less susceptible to being intercepted and a more effective deliverymechanism,” says Pedro J.J. Alvarez, chairman of Rice’s Civil and Environmental EngineeringDepartment. The nanoparticle form is therefore used to ferry silver ions to bacteria they could notreach on their own, for example, by coating devices such as catheters. Silver ions are released fromthe particles in the presence of oxygen [70]. On the other hand, he adds, “We don’t want to over treateither, because silver is an expensive disinfectant and causes collateral environmental damage.”Engineered Ag-NPs have been detected in waterways, and laboratory studies have shown they can betoxic to higher organisms including ryegrass [71], algae [72], the nematode Caenorhabditiselegans[73] and fathead minnows [74] in addition to their potential effects on native microbial populations.The Ag-NPs have been demonstrated as an effective biocide against broad-spectrum bacteriaincluding both Gram-negative and Gram-positive bacteria [75], in which there are many highlypathogenic bacterial strains. To date, there have been many studies on the effects of Ag-NPs againstdifferent bacterial strains. Although some articles proposed different ways to explain the growthinhibition and death of bacterial cells acted on by Ag-NPs [76-78], the exact antibacterial mechanismof Ag-NPs has not been fully understood. Jones and Hoek [75] summarized three most commonantibacterial mechanisms of Ag-NPs as follows: (i) uptake of free silver ions followed by disruptionof ATP production and DNA replication, (ii) Ag-NPs and silver ion generation of reactive oxygenspecies (ROS) and (iii) Ag-NPs direct damage to cell membranes. But, further investigations are stillneeded to demonstrate more clearly this mechanism, especially to explain the affinity of Ag-NPs to


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sulfur- and phosphorus-containing proteins of bacteria, and the effects of this affinity to the functionsof bacterial proteins [79, 80].

Shrivastava et al. [81] described the strong antibacterial potency of novel Ag-NPs in therange of 10–15 nm with increased stability against some strains of non-resistant and drug-resistantbacteria. It was concluded that the antibacterial effect is dose-dependent and is more pronouncedagainst Gram-negative than Gram-positive bacteria; and also independent of acquisition of resistanceby the bacteria against antibiotics. It was also suggested that the major mechanism in which Ag-NPsmanifested antibacterial properties was by anchoring to and penetrating the bacterial cell wall, andmodulating cellular signaling by dephosphorylating putative key peptide substrates on tyrosineresidues.

Sondi and Salopeck-Sondi [76] reported the antimicrobial activities of Ag-NPs against thegrowth of E. coli on Luria–Bertani agar plates. In their study, the E. coli bacterial strain served as amodel of Gram-negative bacteria. Results showed that the growth inhibition of E. coli was dependenton the concentration of Ag-NPs and the initial concentration of cultivated bacteria. The growthinhibitory concentrations were found to be about 50–60 and 20μg cm−3 for 105 CFU and 104 CFU of E.coli respectively. The bacterial cells were damaged and destroyed along with the accumulation of Ag-NPs in the bacterial membrane. Morones et al. [82] have also used different types of Gram-negativebacteria to test the antibacterial activities of Ag-NPs in the range of 1–100 nm. Finally they reportedthat the antibacterial activity of Ag-NPs against Gram-negative bacteria divided into three steps: (i)nanoparticles mainly in the range of 1–10 nm attach to the surface of the cell membrane andremarkably disturb its proper functions, like permeability and respiration; (ii) they are able topenetrate inside the bacteria and cause further damage by possibly interacting with sulfur- andphosphorus-containing compounds such as DNA; (iii) nanoparticles release silver ions, which willhave an additional contribution to the bactericidal effect of Ag-NPs. Kim et al. [77] have used amodel of both Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria to investigate theantibacterial activities of Ag-NPs. Their studies revealed that E. coli is inhibited at a lowconcentration of Ag-NPs (3.3 nM), and ten times less than the minimum inhibitory concentration onS. aureus (33 nM).

In a comparative study of the effect of the Ag-NPs in different shapes on the Gram-negativebacterium, Pal et al. [78] have demonstrated that Ag-NPs undergo shape-dependent interaction withE. coli. Truncated triangular silver nanoplates with a {111} lattice plane as the basal plane displayedthe strongest biocidal action, compared with spherical and rod-shaped nanoparticles, and with ionicsilver. Furthermore, Guzman et al. [83] have reported the results of antibacterial activities ofsynthesized Ag-NPs against E. coli, P. aeruginosa and S.aureus around 14.38, 6.74, and 14.38 ppmrespectively. Kvitek et al. [84] have reported that the antibacterial activity of Ag-NPs is alsodependent on surface modifications (surfactant/polymers). In their study, different types ofsurfactants/polymers (sodium dodecyl sulfate-SDS and polyoxyethylenesorbitanemonooleate-Tween80), and one polymer (polyvinyl pyrrolidone-PVP 360) were used. These stabilized Ag-NPs weretested with some bacterial strains including S. aureus, E. faecalis, E. coli and P. aeruginosa, and otherstrains isolated from human clinical samples such as P. aeruginosa, methicillin-susceptible S.epidermidis, methicillin-resistant S. aureus, vancomycin-resistant E. faecium and K. pneumonia. Theobtained results showed the minimum inhibitory concentrations (MICs) of Ag-NPs in the range of1.69–13.5μg ml−1, depending on bacterial strains, and the use of surfactants/polymers. Specifically,the antibacterial activity of the Ag-NPs was significantly enhanced when modified by SDS where theMIC decreased under the ‘magical value’ of 1μg ml−1. Le et al. [79, 80, 85-87] studied; Ag-NPs weresynthesized by different techniques and tested with several bacterial strains such as E. coli, S. aureusand V. cholera etc. The low MICs were found against these bacterial strains [79, 80, 85-87].Especially, oleic acid stabilized-Ag-NPs showed the MIC against E. coli as low as 1μg ml−1 [85]. Theincreasing number of drug-resistant bacteria has become a major challenge endangering humanhealth. Ag-NPs have been also demonstrated as an effective biocide against these drug-resistantstrains [75, 84, 88 and 89]. Lara et al. [88] have tested the antibacterial activities of commercial Ag-NPs (100 nm) and results revealed a minimum inhibitory concentration (on average) at 79.4 nM fordrug-resistant bacteria such as Erythromycin-resistant Streptococcus. Pyogenes (66.7nM), ampicillin-resistant E. coli O157:H7 (83.3 nM) and multidrug-resistant P. aeruginosa (83.3 nM), and at 74.3nMfor drug-susceptible tested bacterial strains. The result also showed the MICs at100 nM for


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methicillin-resistant S. aureus (MRSA), and at200nM for drug-susceptible S. aureus. Of course, withobserved excellent antibacterial properties, Ag-NPs have been suggested as effective broad-spectrumbiocides against a variety of drug-resistant bacteria, and a potential candidate for use inpharmaceutical and medical products in order to prevent the transmission of drug-resistant pathogensin different clinical environments [90].

3.2. Antifungal effectsAlthough the antibacterial activities of Ag-NPs are well-known, the antifungal activities of

this material have not yet been studied adequately. Now-a day’s Ag-NPs have also been used as apotential biocide against fungal strains, and could help to prevent fungal infections for protection ofhuman health. Fungi are increasingly recognized as major pathogens in critically ill patients,especially nosocomial fungal infections [91]. Kim et al. [92] studied the antifungal activities of Ag-NPs against a total of 44 strains of six fungal species from clinical isolates and ATCC strains ofTrichophytonmentagrophytes (T. mentagrophytes) and Candida albanicans (C. albanicans).Resultsshowed 80% inhibitory concentration (IC80) from 1 to 7μg ml−1. The antifungal activity of Ag-NPsagainst C. albanicans could be exerted by disrupting the structure of the cell membrane and inhibitingthe normal budding process due to the destruction of the membrane integrity [93]. Mendes et al. [94]reported Ag-NPs with sizes of ~ 52 nm possess significant antifungal properties against Phmopsissp., and the inhibitory effects increases as the concentrations of silver nanoparticles increase and Ag-NPs at concentrations greater than 180 µg ml−1 are significantly inhibiting the growth Phomopsis sp.Xia et al. [95] reported that silver nanoparticles have good antifungal activity against T.asahii, theydemonstrate it on the basis of electron microscopy observations that Ag-NPs may inhibit the growthof T.asahii by permeating the fungal cell along with damaging the cell wall and cellular components.In another publication, Roe et al. [96] have tested the antifungal activity of plastic catheters coatedwith Ag-NPs (~ 100 nm thick) and results showed that the growth inhibition was almost complete forC. albicans. Pamacek et al. [97] investigated the antifungal activity of Ag-NPs prepared by themodified Tollens process their results also revealed the minimum inhibition against C. albicansgrowth at 0.21 mg −1 using naked Ag-NPs and 0.05 mg l−1 using Ag-NPs modified with sodiumdodecyl sulfate (SDS). Additionally, Ag-NPs effectively inhibited the growth of the tested yeasts atthe concentrations below their cytotoxic limit against the tested human fibroblasts determined at aconcentration equal to 30 mg l−1 of Ag-NPs. Other reported MICs of Ag-NPs from 0.4 to 3.3μg ml−1

against C. albicansand C. glabrata adhered cells and biofilm [98], and at 10μg ml−1 againstTrichophytonrubrum (T. rubrum) [99].

3.3. Antiviral effectsAg-NPs have shown effective activities against micro organisms including bacteria and

fungi. However, the antiviral activities of Ag-NPs are still challenge to researchers. In recent years,there was an increase in reported numbers of infectious diseases caused by viruses such as SARS-Cov, influenza A/H1N1, influenza A/H5N1, HIV, HBV, Dengue virus and new encephalitis virusesetc. These viral infections are likely to break out into highly infectious diseases endangering publichealth [100]. Very few papers have been found that investigate the effects of Ag-NPs against viruses.Elechiguerra et al. [101] have investigated the interaction between Ag-NPs and HIV-1. It wasreported that Ag-NPs undergo a size-dependent interaction, with NPs exclusively in the range of 1–10nm attached to the virus. It was also suggested that Ag-NPs interact with the HIV-1 virus viapreferential binding to the exposed sulfur-bearing residues of the gp120 glycoprotein knobs, resultingin the inhibition of the virus from binding to host cells. Lara et al. [102] explain this mechanism andreported that Ag-NPs exert anti-HIV activity at an early stage of viral replication, most likely as avirucidal agent or as an inhibitor of viral entry. The Ag-NPs bind to gp120 in a manner that preventsCD4-dependent virion binding, fusion, and infectivity, acting as an effective virucidal agent againstcell-free virus (laboratory strains, clinical isolates, T and M tropic strains, and resistant strains) andcell-associated virus. Besides, Ag-NPs inhibit post-entry stages of the HIV-1 life cycle.

De Gusseme et al. [103] produced the bio-Ag-NPs (called biogenic Ag°) and tested theantiviral activities of biogenic Ag° and ionic Ag+ against murine norvirus 1. The results showed thatin the disinfection assay with ionic Ag+, only a small decrease in genomic copies was detected.Exposure to biogenic Ag° did not result in a significant decrease in genomic copies as well. Incontrast, the plaque assays demonstrated that the infectivity of MNV-1 was completely inhibited. It


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was concluded that the inactivation mechanism of MNV-1 is the interaction of biogenic Ag° with (thethiol groups of) the MNV-1 capsid proteins, making the RNA accessible and rendering the virusparticle non infectious due to favorable interaction with smaller nanoparticles.

Lu et al. [104] investigated the effects of Ag-NPs of different sizes (10, 50 and 800 nm) onthe hepatitis B virus (HBV) and using a HepAD38 cell line as infection model and reported that onlyAg-NPs could inhibit production of HBV RNA and extracellular virion sin vitro. Sun et al. [105] haveutilized Ag-NPs conjugated with (N-vinyl-2-pyrrolidone) (PVP), recombinant respiratory syncytialvirus (RSV) fusion (F) protein, and bovine serum albumin (BSA) in order to study the inhibition ofRSV infection in HEp-2 cell culture. The results revealed that PVP-coated silver nanoparticles, whichshowed low toxicity to cells at low concentrations, inhibited RSV infection by 44%, a significantreduction compared to other controls. It was concluded that when the PVP-coated Ag-NPs mixed withRSV, they would bind to the G proteins on the viral surface and interfere with viral attachment to theHEp-2 cells resulting in the inhibition of viral infection. Monkey pox virus was tested with Ag-NPs indifferent sizes and surface coatings. Initially the results showed that both polysaccharide-coated Ag-NPs (25 nm) and non-coated Ag-NPs (55 nm) exhibit a significant (P 6 0.05) dose-dependent effect oftest compound concentration on the mean number of plaque-forming units (PFU), and Ag-NPs ofapproximately 10 nm inhibit MPV infection in vitro [106].

Xiang et al. [107] investigated the inhibitory effects of Ag-NPs on H1N1 influenza A virusin vitro and reported that Ag-NPs have efficient inhibitory activity on H1N1 influenza A virus, whichcan rapidly inhibit H1N1 influenza A virus hem agglutination of chicken RBCs. In addition, Ag-NPscould also reduce H1N1 influenza A virus induced apoptosis toward MDCK cells. However, theauthors also proposed to clarify how Ag-NPs inhibit H1N1 influenza A virus infectivity as well as theapplication of Ag-NPs to be an effective drug against influenza. Gaikwad et al. [108] reported theproduction of silver nanoparticles from different fungi and demonstrate that silver nanoparticlesundergo a size-dependent interaction with herpes simplex virus types 1, 2 and with human Parainfluenza virus type 3. In his study these silver nanoparticles are capable of reducing viral infectivity,probably by locking interaction of the virus with the cell, which might depend on the size and zetapotential of the silver nanoparticles. In summary of the antiviral effects of Ag-NPs, most publicationshave suggested that Ag-NPs could bind to outer proteins of viral particles, resulting in inhibition ofbinding and the replication of viral particles in cultured cells. Although the antiviral mechanism ofAg-NPs has not been fully known yet, Ag-NPs are still suggested as potential antiviral agents in thefuture [109].

4. TOXICOLOGY OF SILVER NANOPARTICLES TO HUMANS AND THE ECOLOGYNano science and Nanotechnology has been rapidly growing with utilization in a wide

range of Nanomaterial. However, there is still a lack of information concerning the increase of human,animal and ecological exposure to Ag-NPs and the risks related to their short and long-term toxicity.Some possible risks of Ag-NPs to mammalian cells in vitro, in vivo and the toxic effects are discussedbelow.

4.1. In vitro testsGenerally, in in vitro tests, the mechanism of Ag-NPs-mediated cytotoxicity is mainly

based on the induction of ROS. Particularly, exposure to Ag-NPs causes’ reduction in GSH, elevatedROS levels, lipid peroxidation and increased expression of ROS responsive genes, it also leads toDNA damage, apoptosis and necrosis. The cytotoxicity and genotoxicity of Ag-NPs are size-,concentration- and exposure time-dependent.

Kittler et al. [110] have demonstrated that the toxicity of Ag-NPs increases during storagebecause of slow dissolution under release of silver ions. The NPs could release up to 90% of theirweight depending on the functionalization as well as on the storage temperature. The release of silverwas suggested as a considerably increased toxicity of Ag-NPs which had been stored in dispersion forseveral weeks toward human mesenchymal stem cells due to the increased concentration of silverions.Jain et al. [111] were selected Hep G2cells for evaluation of in vitro toxicity of silvernanoparticles. The toxicity of chemically synthesized silver nanoparticles in the presence of plantextract (capped protein silver nanoparticles) was evaluated on these cells with a specificmitochondrial marker (XTT assay) by Paknikar [112]. Results obtained showed a decrease ofmitochondrial function in cells exposed to silver nanoparticles (12.5–400 mg/mL) in a dose-dependent


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manner. The IC50 value of silver nanoparticles was found to be 251 mg/mL [111].Safaepour et al.[113] studied the cytotoxicity of silver nanoparticles at different concentrations (1, 2, 3, 4, 5 µg/mL)in fibro sarcoma-Wehi 164 cells. The particles were prepared with geraniol oil in the presence ofpolyethylene glycol 4000 and a silver nitrate solution in a microwave oven. Cytotoxicity analyses ofthe samples showed a direct dose–response relationship, increasing at higher concentrations. The IC50of silver nanoparticles was 2.6µg/mL. Hackenberg et al. [114] also reported cytotoxic effects of Ag-NPs (46±21 nm) at concentrations of 10μg ml−1 for all test exposure periods to hMSCs. Kawata et al.[115] have reported the in vitro toxicity of Ag-NPs at non-cytotoxic doses to HepG2 human hepatomacells. Results showed that Ag-NPs accelerate cell proliferation at low doses (<0.5 mg/l−1). However,only Ag-NPs exposure exhibited a significant cytotoxicity at higher doses (>1.0 mg l−1) and induceabnormal cellular morphology, displaying cellular shrinkage and acquisition of an irregular shape.Park et al. [116] have showed cytotoxicity to mouse peritoneal macrophage cell line (RAW264.7) byincreasing sub G1 fraction which indicates cellular apoptosis. Ag-NPs decreased intracellularglutathione level, increased nitric oxide secretion, increased TNF-α in protein, gene levels andincreased gene expression of matrix metalloproteinases (MMP-3, MMP-11 and MMP-19). It wassuggested that Ag-NPs were ionized in the cells to cause cytotoxicity by a Trojan-horse typemechanism. Hussain et al. [117] have used the in vitro rat-liver-derived cell line (BRL 3A) to evaluatethe acute toxic effects of metal/metal oxide NPs including silver (Ag; 15, 100 nm), molybdenum(MoO3; 30,150 nm), aluminum (Al; 30, 103 nm), iron oxide (Fe3O4; 30, 47 nm) and titanium dioxide(TiO2; 40 nm). They showed that mitochondrial function decreases significantly in cells exposed toAg-NPs at 5–50μg ml−1. Fe3O4, Al, MoO3 and TiO2 had no measurable effect at lower doses (10–50μgml−1), while there was a significant effect at higher levels (100–250μg ml−1). Lactate dehydrogenase(LDH) leakage significantly increased in cells exposed to Ag-NPs (10–50μg ml−1). Other NPs havebeen tested to displayed LDH leakage only at higher doses (100–250μg ml−1). They concluded thatthe significant depletion of reduced glutathione (GSH) level, reduced mitochondrial membranepotential and increase in ROS levels suggesting that cytotoxicity of Ag (15, 100 nm) in liver cells islikely to be mediated through oxidative stress.

Braydich-stolle et al. [118] have assessed the suitability of a mouse spermatogonial stemcell line to assess toxicity of silver (Ag-15 nm), molybdenum (MoO3-30 nm) and aluminum (Al-30nm) NPs in the male germ line and revealed that a concentration-dependent toxicity for all types oftested NPs. Ag-NPs were the most toxic (5–10μg ml−1) and reduced mitochondrial function drasticallyand increased membrane leakage. This cell line was suggested as a valuable model with which toassess the cytotoxicity of NPs in the germ line in vitro. Arora et al. [119] have studied the interactionof synthesized Ag-NPs with HT-1080 (human fibro sarcoma) and A431 (human skin/carcinoma) cellsin vitro. Results showed that a concentration of Ag-NPs was safe in the range. From 1.56 to 6.25μgml−1 and some effects appeared when concentrations increases to 6.25μg ml−1. They have alsoinvestigated the in vitro interactions of 7–20 nm spherical Ag-NPs with primary fibroblasts andprimary liver cells isolated from Swiss albino mice. Upon exposure to Ag-NPs for 24 h, IC50 valuesfor primary fibroblasts and primary liver cells were 61 and 449μg ml−1 respectively. It was suggestedthat although Ag-NPs seem to enter the eukaryotic cells, cellular antioxidant mechanisms protect thecells from possible oxidative damage [120]. In relation to, the genotoxicity of Ag-NPs followingexposure to mammalian cells. Ahamed et al. [121] have examined the DNA damage response topolysaccharide surface functionalized (coated) and non-functionalized (uncoated) Ag-NPs in twotypes of mammalian cells: mouse embryonic stem (mES) cells and mouse embryonic fibroblasts(MEF). Results revealed that the different surface chemistry of Ag-NPs induces different DNAdamage response: coated Ag-NPs exhibited more severe damage than uncoated Ag-NPs.Calson et al. [122] have investigated evaluating size-dependent cellular interactions of biologicallyactive Ag-NPs (Ag-15, Ag-30 nm and Ag-55 nm) after 24 h of exposure, results showed that viabilitymetrics significantly decreased with increasing dose (10–75μg ml−1) of Ag-15 and Ag-30 nm. With amore than ten-fold increase of ROS levels in cells exposed to 50μg ml−1Ag-15 nm, results suggestedthat the cytotoxicity of Ag-15 nm is likely to be mediated through oxidative stress; this mechanismwas then supported by the study on human hepatoma cells [123].Asha Rani et al. [124] have investigated the cytotoxicity and gene toxicity of starch coated Ag-NPs tonormal human lung fibroblast cells (IMR-90) and humanglioblastoma cells (U251). The resultssuggested mitochondrial dysfunction, induction of ROS by Ag-NPs which in turn set off DNA


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damage and chromosomal aberrations. A possible mechanism of toxicity was proposed whichinvolves disruption of the mitochondrial respiratory chain by Ag-NPs leading to production of ROSand interruption of ATP synthesis, which in turn causes DNA damage. It was anticipated that DNAdamage is augmented by deposition, followed by interactions of Ag-NPs to the DNA leading to cellcycle arrest in the G2/M phase. To investigate the effects of Ag-NPs on skin, Zanette et al. [125] haveperformed their study on the human-derived keratinocyte HaCaT cell line model. Ag-NPs caused aconcentration- and time-dependent decrease of cell viability, with IC50 values of 6.8±1.3μM (MTTassay) and 12±1.2μM (SRB assay) after 7 days of contact. Results also demonstrated that on HaCaTkeratinocytes, a relatively short time of contact with Ag-NPs causes a long-lasting inhibition of cellgrowth, not associated with consistent Ag-NPs internalization. Greulich et al. [126] have reported theinfluence of spherical Ag-NPs (diameter about 100 nm) on the biological functions of humanmesenchymal stem cells (hMSCs). Results showed a concentration-dependent activation of hMSCs atnanosilver levels of 2.5μg ml−1 and cytotoxic cell reactions occurred at Ag-NPs concentrations above5μg ml−1.

Recently, Asare et al. [127] have investigated the cytotoxic and genotoxic effects ofnanoparticles such as Ag-NPs (20 nm) and submicron- (200 nm) size along with titanium dioxidenanoparticles (TiO2-NPs; 21 nm) in testicular cells. The results revealed that silver nano- andsubmicron-particles (Ag-NPs) are more cytotoxic and cytostatic compared to TiO2-NPs, causingapoptosis, necrosis and decreased proliferation in a concentration and time-dependent manner. The200 nm Ag-NPs in particular appeared to cause a concentration-dependent increase in DNA-strandbreaks in NT2 cells, whereas the latter response did not seem to occur with respect to oxidative purinebase damage analyzed with any of the particles tested. Other publications demonstrating thecytotoxicity and genotoxicity of Ag-NPs tested in vitro to human monocytic cell line [128];peripheral blood mononuclear cells (PBMCs) [129]; monocytic cell line THP-1(ATCC 202) [130];human mesenchymal stem cells [114]; human lung carcinoma epithelial-like cell line [131]; primarytesticular cells [127]; and human intestinal cell line [132] have been reported.

4.2. In vivo testsGenerally, very few papers on the in vivo toxicology of Ag-NPs were found, so further

investigation is needed in this field to evaluate exactly the real impact of Ag-NPs in commercialproducts to humans and animals. Due to the ultra-small sizes of Ag-NPs, a great mobility is conferredin different environments, and humans are easily exposed via routes such as inhalation, ingestion,skin, etc. Ag-NPs can translocate from the route of exposure to other vital organs and penetrate intocells. The impact of Ag-NPs to environment and ecology has been discussed in detail by Ahamed et al[15]. Takenaka et al. [133] studied systemic pulmonary distribution of inhaled ultrafine Ag-NPs (4–10nm) in rats. The authors verified low concentrations of silver in the liver, kidney, spleen, brain andheart. The level of silver in the liver, lungs and blood decreased rapidly with time. Nasal cavities andlung-associated lymph nodes showed relatively high concentrations. The fast clearance of ultrafinesilver nanoparticles can be due to rapid solubilization of these particles in the lung and silvernanoparticles enter the blood capillaries by diffusion. In a similar study Sung et al. [134] reported thatRats were exposed to Ag-NPs (18 nm) for 90 days to evaluate the in vivo effect of particle inhalation.Chronic alveolar inflammation, including thickened alveolar walls and small granulomatous lesionswas observed after Ag-NPs exposition, indicating lung function changes. Toxicity andbiocompatibility of Ag-NPs were evaluated in vivo using zebra fish embryos [135]. The embryoswere treated with spherical Ag-NPs with sizes of 11.6 ±3.5 nm. They observed that a single silvernanoparticle was transported into and out of embryos through chorion pore canals. Furthermore, thebiocompatibility and toxicity of Ag-NPs and types of abnormalities observed in zebra fish are highlydependent on the dose of particles, with a critical concentration of 0.19nmol/L.

Kim et al. [136] have tested the oral toxicity of Ag-NPs (60 nm) over a period of 28 days inSprague-Dawley rats. Results showed that the male and female rats did not show any significantchanges in body weight relative to the doses of Ag-NPs during the 28-day experiment. But, somesignificant dose-dependent changes were found in the alkaline phosphatase and cholesterol values ineither the male or female rats, seeming to indicate that exposure to over more than 300 mg of Ag-NPsmay result in slight liver damage. It was suggested that Ag-NPs do not induce genetic toxicity in male


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and female rat bone marrow in vivo. Other publications reported concerning the studies on toxicologyof Ag-NPs to organism via skin exposure or injection [137, 138]. For inhalation toxicity of Ag-NPs, Ji et al. [139] have investigated the inhalation toxicity of Ag-NPs on Sprague-Dawley rats over a period of 28 days. The rats were exposed to the Ag-NPs for 6 hper day, 5 days per week, for a total of 4 weeks. Results showed that the male and female rats did notshow any significant changes in body weight relative to the concentration of Ag-NPs during the 28-day experiment. There were no significant changes in the hematology and blood biochemical valuesin either the male or female rats. Whereas, some investigators have reported that lungs are majortarget tissues affected by prolonged inhalation exposure to Ag-NPs [140]. In another publication, Lee et al. [141] have reported Ag-NPs exposure modulated theexpression of several genes associated with motor neuron disorders, neurodegenerative disease andimmune cell function, indicating potential neurotoxicity and immune toxicity associated with Ag-NPsexposure. Minimal pulmonary inflammation or cytotoxicity of mice was found after 10 days of Ag-NPs exposure [142]. For gastrointestinal toxicology caused by Ag-NPs exposure via ingestion,Common causes of Ag-NPs-induced toxicity include oxidative stress, DNA damage and apoptosis.

5. CONCLUSIONSThe unique physical, chemical and antimicrobial properties of Ag-NPs only increase the

efficacy of silver. They have been widely used for electronic, computers, textile industries, Nanosilver based disinfectant and biomedical products. In this review, a brief description of Ag-NPssynthesis methods, antimicrobial effects and possible toxicology considerations of Ag-NPs to humanand environments mentioned. Ag-NPs were synthesized by various physical, chemical, photochemicaland biological processes but the biological synthesis is the more preferred option. Though bacterial,fungal, and plant extract sources can be used for synthesis of Ag-NPs, the advantage of quickersynthesis make plant extracts the best and an excellent choice for Ag-NPs synthesis. Antimicrobialproperties of Ag-NPs and its potential mechanisms against fungus, bacteria and virus were described.Toxicology consideration of different Ag-NPs to human health and ecology along with the possiblerisks of Ag-NPs to mammalin cells in vitro and in vivo discussed. Generally higher concentrations ofAg-NPs are toxic, causes various health problems, induce various ecological problems and disturb theecosystem if released into the environment. However, further investigation is needed that there wouldbe mechanisms devised to nullify the toxicity caused by Ag-NPs to human and environments so thatthe unique properties of this substance can be put to great use of society without controversies.6. REFERENCES[1] Sergeev, G. B. Nano chem 2006 Elsevier.[2] Sergeev, G. B.; Shabatina, T. I. Colloids Surf A Physicochem Eng Aspects 2008, 313,18.[3] Sergeev, G. B. J Nanoparticle Res 2003, 5, 529.[4] Williams, D. Biomaterials 2008, 29, 1737.[5] Saifuddin, N.; Wong, C. W.; NurYashumira, A. A. E J Chem 2009, 6, 61.[6] Dahl, J. A.; Maddux, B. L.; Hutchison, J. E. Chem Rev 2007, 107, 2228.[7] De, M.; Ghosh, P. S.; Rotello, V. M. Adv Mater 2008, 20, 4225.[8] Lu, A.H.; Salabas, E. L.; Ferdi, S. Angew Chem Int Ed Engl 2007, 46, 1222.[9] Ghosh, C. R.; Paria, S. Chem Rev 2012, 112, 2373.[10] Sharma, V. K.; Yngard, R. A.; Lin, Y. Adv Colloid Sur Interface 2009, 145, 83.[11] Krutyakov, Y. A.; Kudrynskiy, A. A.; Olenin, A. Y.; Lisichkin, G. V. Russ Chem Rev 2008, 77, 233.[12] Monteiro, D. R.; Gorup, L. F.; Takamiya, A. S.; Ruvollo-Filho, A. C.; De.; Barbosa, D. B. AntimicrobAgents 2009, 34, 103.[13] Slawson, R. M.; Trevors J. T.; Lee, H. Arch Microbiol 1992, 158, 398.[14] Zhao, G. J.; Stevens, S. E. Biometals 1998, 11, 27.[15] Ahamed, M.; Alsalhi, M. S.; Siddiqui, M. K. Clin Chim Acta 2010, 411, 1841.[16] Garc´ıa-Barrasa, J.; L´opez-de-luzuriaga, J. M.; Monge, M. Cent Eur J Chem 2011, 9, 17.[17] Fabrega, J.; Luoma, S. N.; Tyler, C. R.; Galloway, T. S.; Lead, J. R. Environ Internat 2011, 37, 517.[18] Dallas, P.; Sharma, V. K.; Zboril, R. Adv Colloid Interface Sci 2011, 166, 119.[19] Rai, M.; Yadav, A.; Gade, A. Biotechnol Adv 2009, 27, 76.[20] Sundaramoorthi, C.; Devarasu, S.; VengadeshPrabhu, K. Int J Pharm Res Dev 2011, 2, 69.[21] Ravichandran, R. Nanobiotechnology 2009, 5, 17.[22] Jones, K. E.; Patel, N. G.; Levy, M. A.; Storeygard, A.; Balk,D.; Gittleman, J.L.; Daszak, P. Nature 2008,451, 990.

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[142] Stebounova, L.V.; Adamcakovadodd, A.; Kim, J.S.; Park, H.; Shaughnessy, P.T.O.; Grassian, V. H.;Thorne, P. S. Part Fibre Toxicol 2011, 8, 5.

AUTHOR’S BRIEF BIOGRAPHY

Prof (Dr.) Sanjay Kumar Rout : He received his M.Sc. and Ph.D. degrees in Chemistry fromUtkal University, Bhubaneswar, India. He has started his career as a lecturer in 1998. He haspublished 15 research papers in the field of Polymer Composites. Presently he is working as aProfessor in Chemistry at Konark Institute of Science and Technology, Bhubaneswar. His researchinterests are Modification of Lignocellulosic Fiber and Polymer Nanocomposites.

Prof. (Dr) Bikash Ranjan Kar: He presently worked as Professor in Dept of Skin & VD, IMS &SUM Hospital, SOA University, Bhubaneswar-3, completed MD in Dermatology from theprestigious PGIMER, Chandigarh in 2001 and joined Schieffelein Leprosy Research & Trainingcenter at Vellore in 2002 to pursue his career in the field of clinical research. Worked with theiconic Dr C K Job for 3 years and published approx. 10 papers with him. Major work area wasleprosy and manages to publish few dermatology related papers during that time as well. In 2005joined Institute of Medical Sciences & SUM hospital at Bhubaneswar and started the skindepartment. He awarded with membership of National Academy of Medical Sciences in 2012.First time reported the largest series of Hand Foot Mouth disease in Orissa, which got published inNational Medical Journal of India and Indian Pediatrics Golden Jubilee issue, with more than 30publications in National & International peer reviewed journals.

Prof (Dr.) Payodhar Padhi : He completed M.Tech and PhD from IIT, Kharagpur currentlyworking as a Principal of Konark Institute of Science and Technology, Bhubaneswar. In additionto this he is the Dean (Research & development) of Hi-Tech Medical College and Hospital. He isthe Coordinator of Industry Institute Partnership cell established by AICTE, Govt of India &Business Incubator center established by Ministry of Micro Small & Medium Enterprise, Govt. ofIndia. He guided six no of PhD student in different areas. To his credit he published 75 nos ofpapers in both International journal and proceedings. He is a consultant to different Industries interm of product development, design etc. He is one of the registered design consultants to NID,Ahmadabad. He has received several awards in different levels.

Prof. (Dr) Bankim Chandra Tripathy : He completed his PhD in 2000 at Utkal University,Bhubaneswar, India, under Dr S. C. Das (CSIR-IMMT) and Professor Glenn Hefter (MurdochUniversity). Subsequently, he took up postdoctoral research with Professor Pritam Singh atMurdoch University. He then joined CSIR-IMMT as a scientist in 2004. In 2007 he took upanother postdoctoral at MINTEK, South Africa. Under Raman Research Fellowship Program ofCSIR, he had been to the Materials Engineering Department, UBC, Canada, as a visiting facultywhere he worked with Professor Akram Alfantazi. At present he is a Principal Scientist at CSIR-IMMT and Associate Professor in Chemical Sciences with Academy of Scientific and InnovativeResearch (AcSIR). His research domain falls in the area of Materials Science and ExtractiveMetallurgy.

Prof. (Dr) Krushna Gopal Mishra: He completed his Post graduation in Chemistry on 1981.Subsequently he obtained his Ph.D in chemistry from Utkal University, Vanivihar, Bhubaneswar.Besides, having nearly 26 years of teaching experience, Dr. Mishra also has wide exposure inResearch and Development during his association with CSIR-IMMT. At present Dr. Mishra is aProfessor in Chemistry and is with School of Applied Sciences, KIIT University, Bhubaneswar. Inaddition to teaching & research, Dr. Mishra has been shouldering the administrative responsibilityin different capacities at KIIT University. He has published more than 30 research papers invarious national and International journals of repute and has one patent to his credit. He has visitedPerth and Melbourne in Australia in connection with his Research. His research interest pertains tothe broad area of Electrochemistry and in specific to Corrosion, Electrodeposition, Electrolessdeposition, Electro leaching and electrokinetics.


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Documents

A Review on Synthesis, Antimicrobial Effects and