Silver Nanoparticles: Properties, Synthesis ...

27 May.,2024

 

Silver Nanoparticles: Properties, Synthesis ...

Nanotechnology is an expanding area of research where we use to deal with the materials in Nano-dimension. The conventional procedures for synthesizing metal nanoparticles need to sophisticated and costly instruments or high-priced chemicals. Moreover, the techniques may not be environmentally safe. Therefore &#;green&#; technologies for synthesis of nanoparticles are always preferred which is simple, convenient, eco-friendly and cost effective. Green synthesis of nanoparticle is a novel way to synthesis nanoparticles by using biological sources. It is gaining attention due to its cost effective, ecofriendly and large scale production possibilities. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. It has vital importance in nanoscience and naomedicines to treat and prevent vital disease in human beings especially in cancer treatment. In current work we discussed different methods for synthesis of AgNPs like biological, chemical and physical along with its characterization. We have also discussed vital importance of AgNPs to cure life threatnign diseases like cancer along with antidiabetic, antifungal, antiviral and antimicrobial alog with its molecular mode of action etc. Finally we conclude by discussing future prospects and possible applications of silver nano particles.

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1. Introduction

Currently, improving and protecting our environment using green chemistry have become important issues in many fields of research. The most promising approach for generating new fields in biomedical sciences is the pharmaceutical application of nanoparticles (NPs) [1]. Due to ascension of industrial era and explosion of world population large amount of hazardous chemicals and gases released in environment in which adversely affecting our nature. Due avoid this and to protect our nature currently we world is focusing on development of natural products nanoparaticles. Biomolecules are highly compatible with nanotechnology which makes unique assembly for development of metal nanoparticles of biological molecules which are authentic and coast effective [2]. From the ancient era noval medicinal potential of silver has been known and proven for its antimicrobial potential [3]. Silver nano particles (AgNPs) and its related products were tremendously venomous and showed broad spectrum antibacterial potential against sixteen bacterial species [4, 5]. Nanotechnology is future era in material science which develops and upgrades qulaites of particles such as size, and morphology which provide entry of nonmaterial in future quality material building in almost every field [6]. Nanotechnologies have been used to develop nanoparticles-based targeted drug carriers [7]. Metal nanoparticles have a high specific surface area and a high fraction of surface atoms because of the unique physicochemical characteristics of nanoparticles [8, 9]. In that they include catalytic activity, optical properties and electronic properties, antibacterial properties, and magnetic properties [10, 11]. The nanoscale materials have emerged as novel &#;antimicrobial agents&#; due to their high surface area to volume ratio and their unique chemical and physical properties [12, 13]. In recent years development of metallic nanoparicles is an emerging field of research in material science. Crystalline nanosilver gained prime importance and has superior applicability in detection of biomolecules, antibacterial, electronics, diagnostic applications in health care system etc. Apart from novel applicability of AgNPs researchers still in search of advance methods to synthesize eco-friendly and coast effective tools to develop AgNPs [14, 15]. As silver posse&#;s broad spectrum potential against bacterial and microbial species which specially utilized in industries it has key role in healthcare systems [16]. Nitrate group of silver potentially responsible for its broad spectrum antibacterial potential and as it convert in to AgNPs surface area is drastically increased which improve microbial exposure time and area [17, 18, 19]. Different techniques are available to synthesize AgNPs such as physical, chemical and biological. Though chemical method is rapid it utilizes capping agents for synthesis which is costly and produces adverse and toxic effects. This demands development of safe, ecofriendly, coast effective tool for synthesis of AgNPs and focused on biological methods such as green synthesis which is non toxic and developed using plant origin materials and overcomes disadvantages of earlier approaches. Moreover, use of plant extracts also reduces the cost of microorganism&#;s isolation and culture media enhancing the cost competitive feasibility over nanoparticles synthesis by microorganisms [20]. Applicability of AgNPs is primly due to its nanoscale size and shape as compared to bulk. Due to these unique properties researchers are hunting of novel methods to synthesize AgNPs with prissily controllable size and shape [21, 22, 23, 24]. Apart from excellent inhibitory potential of AgNPs in recent years most of the pathogenic bacteria developed resistant against it which is major concern of health care system. Chemical and physical approaches consumes ample of time, energy, money and generate toxic side effects. Nowadays green synthesis utilize microbes, fungi and medicinal plants which are easily available, convenient to handle and wide source of metabolites to synthesize AgNPs gained prime importance due to its nontoxic and ecofriendly properties [25]. Currently AgNPs are synthesized from natural herbs having medicinal potential such as synthesis of various metal nanoparticles using fungi like Aspergillus terreus, Paecilomyces lilacinus and Fusarium [26]. Penicillium sp. [27] Fusarium oxysporum [28] and Euphorbia hirata, green tea, neem, starch aloevera, lemon etc. [29, 30, 31, 32]. AgNPs mainly binds to cell wall and penetrate deep inside the cell wall which produces cellular damage by interacting with DNA, proteins inside the cell which leads to cell death [33, 34, 35, 36, 37].

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2. Need for green synthesis and silver nanoparticles

Silver is a basic element which is non-toxic belonging thermal and electrical potential [38]. Silver demand will likely to rise as silver find new uses, particularly in textiles, plastics and medical industries, surgical, dental resigns, coated water filters, sanitizers, detergents, soap and wound dressings. Applicability in healthcare for treatment of mental illness, convulsions, de addiction of narcotic products along with sexually transmitted diseases like syphilis and gonorrhea leads to changing the pattern of silver emission as these technologies and products diffuse through the global economy [39, 40, 41]. Green synthesis is an emerging approach which overcomes demerits of physiochemical approaches by utilization of natural herbs which are nontoxic [42, 43]. Green synthesized nanosilver offer many advantages like utilization of phytochemicals, antioxidants acts as naturally occurring reducing agents, coast efficient, large scale manufacturing highly beneficial and usage of toxic chemicals, high pressure, energy are avoided. Nanosilver can be engineered by different techniques such as irradiation, reduction, electrochemical and chryochemical synthesis. Nanosilver can be molded in to desired shapes and bear unique properties like permeability by pH and dissolved ions as compare to routine metals [44, 45]. As AgNPs generate larger surface area per unit mass which improves contact time nanosilver customer market an demand drastically raised in wide verity of industries along with healthcare, food packing, textiles, cosmetics etc. [46].

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3. Silver nano particles

Generally AgNPs are nanoparticles of silver having size range between 1 and 100 nm in size having unique properties such as electrical, optical and magnetic having wide range of applicability [47]. Green chemistry is and encouraging approach mainly utilize nanosilver along with natural biomolecules such as polysaccharides, tollens which overcomes drawbacks of conventional methods and produce AgNPs which are ecofriedly, nontoxic and coast effective [48, 49]. Metallic silver ions are inactive but once it come contact with reducing agent ionization occurs and it get converted in its active form. Ionic silver is active form of silver which binds to cell wall of bacteria leading to major structural changes in cell morphology. AgNPs causes de-naturation of RNA and DNA replication which further leads to cell death [50]. Silver is also called as oligodynamic due to its bactericidal potential at minimum concentration. That&#;s why it has been largely used in medical products [51, 52].

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4. Methods for synthesis of silver nanoparticle

4.1 Physical approaches

In physical approach of synthesis of AgNPs evaporation and condensation has major importance. Temperature gradient play important role in cooling of vapors at desired rate. A chance of contamination by solvent has been removed by physical approach as no solvent has been used in physical method and uniform distribution of particle size precisely obtained [53, 54]. Minimum inhibitory concentration in toxicity studies can be easily achieved by production of nano scale nanoparticles in high concentration [55]. AgNPs also synthesized by laser ablation of metallic particles [56]. One important advantage of laser ablation technique compared to other methods for production of metal colloids is the absence of chemical reagents in solutions. Therefore, pure and uncontaminated metal colloids for further applications can be prepared by this technique [57]. Wide range of material can be synthesized in nanoparticels by physical method such as Au, Au and PbS etc. Synthesis of AgNPs by tube furnace has ample of disadvantages such as require larger space, high power, rapid rise of environmental temperature etc. AgNPs synthesized by laser ablation strongly depend on laser wavelength, time of laser pulse, laser fluence, the ablation time duration and the effective liquid medium. Ejection of AgNPs synthesized by laser ablation requires little power and particle size is precisely depends on laser fluence. However morphology, size and shape of AgNPs mainly depend on contact of laser light passing. Also, the formation of nanoparticles by laser ablation is terminated by the surfactant coating. The nanoparticles formed in a solution of high surfactant concentration are smaller than those formed in a solution of low surfactant concentration. One advantage of laser ablation compared to other conventional method for preparing metal colloids is the absence of chemical reagents in solutions. Therefore, pure colloids, which will be useful for further applications, can be produced by this method [58, 59].

4.2 Chemical approaches

Chemical reduction is the most frequently applied method for the preparation of AgNPs as stable, colloidal dispersions in water or organic solvents. Most commonly used reductant is citrate. In aqueous solution reduction of silver occurs and nanosize colloidal silver ions are generated. Stability of any colloidal dispersion has prime importance and which could be achieved by stabilizing agent (dodecanethiol) which adsorbed on surface and produce protective sheath. It can avoid agglomeration and crystal growth of the system. During the synthesis of AgNPs minute changes in parameters (Polymers) makes drastic changes in size, shape, morphology, polydispersibility index, self assembling and zeta potential (Stability). Frequently used ingredients in synthesis of AgNPs and AuNPs are glycol derivatives Polyvinyl pyrrolidone (PVP) and Polyethylene glycol (PEG). Polyacrylamide play dual function such as reducing and stabilizing agent in synthesis of AuNPs [59, 60]. Surfactants containing functional groups such as amines, thoils and acids play important role in stability of colloidal dispersion which protects the system from crystal growth, coaleseces and agglomeration. Currently AuNPs developed by modified tollens method utilize saccharides and silver hydrosols and reducing agent which yield AgNPs in the range of 50&#;200 nm and 20&#;50 nm respectively [61].

4.3 Biological approaches

Biotechnology is an emerging tool to develop biological synthesis of AgNPs. Besides this magnetic nanoparticles has great antibacterial potential due to improved surface area to treat raised microbial resistant against many antibiotics and medicines [62]. Currently green chemistry is rapidly growing technique utilized for synthesis of AgNPs with naturally occurring stabilizing, reducing and capping agents to synthesize AgNPs without toxic adverse effects [63]. Reduction of metal ions by combined efforts of herbs and certain enzymes, proteins, microorganisms, bacteria and fungi etc. in biological synthesis has been successfully reported [64].

4.4 Synthesis of silver nanoparticles by fungi

High production yield AgNPs synthesized by fungi obtained when compared to bacteria due to fungi secret higher amount of proteins that directly responsible for increased production [65]. Higher production rate is mainly due to silver ions entered in to fungal cell wall which leads to reduction of silver ions by fungal enzymes such as naphthoquinones and anthraquinones [66]. Slower rate and process is only disadvantage associated with fungal synthesis of AgNPs hence green synthesis approach is more preferred over the other techniques [67].

4.5 Synthesis of silver nanoparticles by bacteria

Pseudomonas stutzeri which is the first strain of bacteria form which AgNPs were synthesized and isolated form Ag amine [68]. Many of the bacterial strains and microorganism developing resistance to metal at lower concentration. Resistance mainly produced due to efflux, change in solubility, toxicity via oxidation/reduction and precipitation of metals [69]. There are evidences that at lower conc. Microorganisms are alive but once exposed to high conc. Metal ions leads to microbial death. In biosynthesis of silver enzyme nitrate reductase convert nitrate to nitrite [70].

4.6 Synthesis of silver nanoparticles by plants

Green synthesis is an excellent tool that can be utilized for synthesis of AgNPs as it uses natural origin medicinal herbs and its extracts which contain wide range of metabolites specifically water soluble flavones, quiones causes rapid rapid and quick reduction of silver when compared to fungi and microbes. Green chemistry approach is safe, cosat efficient, easily scalable to mass productions, easily availability of raw materials at cheaper coast. Phytochemicals directly take part in reduction process of the silver ions a during synthesis of AgNPs (Figure 1) [71].

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5. Mechanism of action of silver nanoparticles

5.1 AgNP&#;s antimicrobial MOA

When AgNP reaches toward cell they release Ag+ ions. These released ion then interact with sulfur and phosphorus containing compound present in cell wall. This lead to disarranged cell wall formation and small pits forms in the cell wall. Formed pit gives access to entry of ions and other foreign material to entry into cell. This increase intracellular osmotic pressure. As pressure built up in the cell, it begins to swell. Finally all these event lead to bursting of cell wall and cell lysis take place. This type of antimicrobial activity is more in gram &#;ve cell than gram +ve cell. As gram +ve cell have more cross linked peptidoglycan layer and teichic acid in their cell wall. The gram &#;ve cell have less or no peptidoglycane layer and have more lipopolysaccharide in their cell wall. So the AgNP&#;s easily interact with gram &#;ve cell due less barrier [72].

5.2 AgNP&#;s anticancer MOA

As described in above when pit formation takes place in the cell wall, the Ag+ ions released by AgNP&#;s get entered into cell. Then they reaches to mitochondria where they interact with thiolgoups and bind to NADPH dehydrogenase enzyme and liberates ROS. These formed ROS in mitochondria interacted with respiratory enzymes damage ATP formation and respiratory cycle of cell. Formed ROS also interact with protein, sulfur and phosphorus containing cell constituent. Also these formed ROS also bind to phosphorus elements of DNA and RNA which lead to inhibit cell replication and protein synthesis. Due to binding with DNA aggregation of damage protein sysnthesis which lead to cell death. Another possible action is by autophagy. AgNP&#;s have ability to induce autophagy by accumulation of autophagolysosmes in human ovarian cancer cell. This autophagy work by mainly 2 ways; at lower level they increases cell life i.e. surviving rate, but when its level increase it lead to cell death (Figure 2) [73].

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6. Factors affecting bactericidal potential of AgNP&#;s

Primarily morphology i.e. size and shape along with reactivity of AgNP&#;s were responsible for bactericidal potential of AgNP&#;s. Size and surface are inversely proportional to each other as size decreases area increases leads of rapid rise in surface-area to volume ratio. Bactericidal potential inhibit cell wall and free radicals Ag-thiol groups of enzymes Preventing biofilm formation Intercalates between bases Attaching to the surface of the cell membrane Bacterial peptides that can affect cell signaling Attaches to 30 s subunit (Figure 3). Silver nanoparticles showing multiple bactericidal actions [74].

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7. Charactrisation of AgNP&#;s

7.1 Visual and UV: Visible study

To ascertain either AgNPs are developed or not visual and calorimetric appearance of samples checked by UV&#;Visible spectrophotometer before and after formulation of AgNPs at different time intervals. Before synthesis of AgNPs silver nitrate is colorless and herbal extract has definite color. Once AgNPs synthesized silver nitrate solution develop yellowish brown color after interacting with herbal extract which is confirmed by surface Plasmon resonance SPR and UV visible absorption in the specific range of 400&#;475 nm [75].

7.2 FTIR analysis

FTIR spectroscopy is an investigational tool to determine/conform functional groups priesnt in the moiety which is characteristic of that compound. Major functional moieties present in AgNPs and herbal extract were identified by scanning the samples in the range of to 400 cm&#;1 [76].

7.3 SEM/TEM analysis

Scanning electron microscopy/Transmission electron microscopy mainly used to study surface morphology of synthesized AgNPs. SEM/TEM plates were prepared by addition of silver nitrate to develop smear of solution on slides. Conductivity was incorporated in system by making thin film of platinum which was coated on slides. Once the slides were ready they were scanned at 20 KV accelerating voltage and high quality images were captured [77].

7.4 X-ray diffraction (XRD) analysis

X-ray diffraction is a modern technique mainly utilized to identify state of matter either it is crystalline or amorphous in nature at different radiation angles. X-ray diffraction determines phases either crystalline/amorphous and cell dimension [78].

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8. Application of silver nanoparticles

8.1 Antimicrobial activity

Products prepared with silver nanoparticles have been permitted by no. of accredited bodies including USFDA, USEPA, Korea&#;s testing body and SIAA of japan institute of research. Antimicrobial and antimicrobial potential potential of AgNPs containing silver sulfadiazine is incorporated in to medicines and used in burns to avoid infections. Nowadays AgNPs involved in extending field of nanotechnology and appears in many consumer products that include acne vulgaris cream and for deodorizing sprays. The antimicrobial properties of silver nanoparticles depend on size, environmental conditions (size, Ph, tonic strength) and capping agent. Recently an improvement in antimicrobial activity synergistic effect has been reported when silver naqnoparticles combined with ampicillin, amoxicillin and chloramphenicol on the contrary reports showed antagonistic interaction between silver nanoparticles and amoxicillin or oxacillin antibiotic combined with silver nanoparticles have suggested improve therapeutic activity (Figure 4) [79, 80].

8.2 Antiviral activity

Antiviral activity of silver nanoparticles have proven to exert antiviral activity against HIV-1 at non cytotoxic concentration but the mechanism underlying their HIV inhibitory activity has not been fully elucidated. The study from intranasal silver nano particles administration in mice increased survical, lower lung viral titer levels, minor pathologic lesions in lung disease, and remarkable survival benefit after infection with the H3N2 influenza virus, suggesting that AgNPs had significant role in mice survival. Biologically prepared silver nano particles inhibited the viability in herpes simplex virus (HSV) types 1 and 2 and human para influenza virus type 3 based on size and zeta potential. The treatment of vero cells with non-cytotoxic concentrations of silver nanoparticles significantly inhibited by the replication of paste des petits ruminants virus (PPRV). The mechanisms of viral replication are due to the interaction of silver nanoparticles with the virion core. Tannic acid mediated synthesis of various various sizes of silver nanoparticles capable of reducing HSV-2 infectivity both in in-vitro and in-vivo through direct interaction, blocked virus attachment, penetration and further spread [81, 82].

8.3 Antibacterial activity

Silver nano particles are one of the most attractive nonmaterial&#;s for commercialization applications. As antibacterial agents silver nanoparticles were used for wide range of applications from disinfecting medical devices and home appliances to water treatment. AgNPs promisingly used in drastic fields such as healthcare products, food storage, textile and medicinal devices. In antibacterial potential AgNPs free silver ions are released at slower rate along with higher surface area which produces noxious environment and this is the main reason for broad spectrum antibacterial potential of AgNPs [83].

8.4 AgNP&#;s in cancer control

AgNPs has prominent anticancer potential as it discourage mitochondrial respiratory chain, increase reactive oxygen species (ROS) rate of synthesis which finally leads to DNA damage and cancerous cell death. Yu-Guo Yuan in revealed that the combination of camptothecin and silver nanoparticles treatment significantly increases the levels of cancer cells. It increases oxidative stress markers and decrease ant oxidative stress markers compared to single treatment. Overall these results suggested that camptothecin and silver nanoparticles cause cell death by inducing the mitochondrial membrane permeability change and activation of caspase. The synergistic cytotoxicity and apoptosis effect seems to be associated with enhanced ROS formation and depletion of antioxidant. Certainly a combination of CPT and silver nano particles provide advantageous effect in treatment of cervical cancer compared to immunotherapy [84].

8.5 Antidiabetic activity of AgNP&#;s

Tephrosiatinctoria stem extracts mediated silver nano particle synthesis was evaluated for control of blood suger levels. AgNP&#;s scavenged free radicals, reduced the levels of enzymes that bring about hydrolysis of complex carbohydrates (α&#;glucosidaseα&#;amylase) and as a result of which there is an increase in consumption ratr of glucose. The promising antidiabetic activity of shown by Ananascomosus (L.) silver nanoparticles. In dose dependent manner. AC-AgNP&#;s inhibit α-glucosidase enzyme in stomach. Which is helpful in non-insulin diabetic patient. Also the silvernanoparticles synthesized with Argyreia nervosaleaf extract shown great antidiabetic activity. They inhibit mainly enzymes that digest the carbohydrates into monosaccharide and reduce blood glucose level [85, 86].

8.6 Different field application of AgNp&#;s

Studies can contracting on the therapeutic applications of AgNP&#;s in the gastrointestinal tract have displayed that gastric cells can be sensitized to radiation by the use of AgNP&#;s and they may bypass the stomach and instead release the drug in small intestine. Apart from the health related applications; Silver Nanoparticles are act as a brilliant heterogeneous catalyst used for reduction of halogenated organic pollutants. Also it increases the bleaching power of organic dyes. The tubular shaped silver Nanoparticles have a very potent catalytic activity so they can used as a catalyst. In case of water treatment when the biosynthesized Silver Nanoparticles which are biologically synthesized on nitrocellulose membrane filters, can used for the promising inhibition and inactivation of microbes like E. coli and Enterococcus faecalis, etc. Rather as the silver Nanoparticles are the very good antimicrobial agents so they are used as the preservatives in various food and agricultural products [87].

8.7 Antifungal activity of AgNPs

AgNP&#;s play important role as antifungal agents against various diseases caused by fungi. Biologically synthesized AgNP&#;s shows enhanced antifungal activity with fluconazole against phomaglomerata, Candida albicans species. AgNP&#;s stabilized by sodium dodecyl sulphate showed greater antifungal activity against Candida albicans compared to conventional antifungal agents. The AgNP&#;s synthesized by bacillus species exhibit strong antifungal activity against the plant pathogenic fungus fusariumoxysporum at concentration of 8 μg/ml. AgNP&#;s shown promising antifungal activity on T. asahii with MIC of 0.5ug/ml by damaging cell wall and components of cell. Due to size of nanoparticles they easily penetrate into cell. Where it binds to different cell components and inhibits cell functions. In combination with antimicrobial agents like ketoconazole shown great antifungal activity with MIC less than 0.5 mg/ml against the Malassezia where they give synergistic effect with ketoconazole it form pores in cell to show antifungal activity [88, 89].

8.8 Anti angiogenic activity of AgNP&#;s

Antiangiogenic potential of green synthesized AgNP&#;s in retinal endothelial cells model mainly produced by inhibition, proliferation and migration of BRECs at 500 nM concentration. In CAM model (chicken embryo chorioallantoic membrane) the silver nanoparticles inhibit angiogenesis approximately up to 73%. In comparison to other antiangiogenic molecules. They give dose dependent cytototoxic action on endothelial cell present in blood vessels to inhibit formation of new blood vessel in tumor region. Also the by using the same model i.e. by CAM assay the silver nanoparticle synthesized by Rubinatinctorum shown antigiogenic activity. Ru-AgNP&#;s shown inhibitory action on blood vessels. In CAM model, there is decrease in length of embryo resulted out due to the antiangiogenic action of Ru-AgNP&#;s [90, 91].

8.9 Diagnostic, biosensor and gene therapy applications of AgNP&#;s

Nanoparticles have advantage over today&#;s therapies because they can be engineered to have certain properties or to in certain way. They are helpful in cellular imaging. Silver plays an important role in imaging systems due to its stronger and sharper Plasmon resonance. Currently biosensor made with silver used as powerful tool to detect cytochrome P53 of squamous cell cancer of head and neck. Due to the colorimetric sensing property the silver Nanoparticles are applicable to detect the heavy metal ions of nickel, cobalt and mercury along with the sulfide traces. Among all the types of silver Nanoparticles, especially the triangular shaped silver Nanoparticles have higher anisotropy and lightening rod effect which leads to its wide use in manufacturing of Plasmon sensors or Plasmon detectors which are used to detect the mercurial ions in the solution. Also the silver Nanoparticles are used to develop the electrochemical sensor which is used to detect common herbicide atrazine. On the other hand the in situ growth and development of silver Nanoparticles on polydopamine traced filter paper is responsible for the quick collection and detection of green colored residue of malachite [92].

8.10 Anti-inflammatory activity of AgNP&#;s

AgNPs have been known for its antimicrobial but the anti-inflammatory response is still limited. Rats treated intra colonic ally with 4 mg/kg or orally with 40 mg/kg of nanocrystalline silver (NP) showed significantly reduced colonic inflammation. AgNPs showed rapid healing and improved cosmetic appreance occurring in dose dependent manner. Silver Nanoparticles made by using the extraction method with petroleum ether and some small amount of ethyl acetate are having potent cyclooxigenase-2 inhibition property. So, as one can add the natural extract of anti-inflammatory activity to this silver Nanoparticles extracted with petroleum ether, the anti-inflammatory activity of the resulted silver Nanoparticles get increased. Recently some scientists were done the extraction of soft coral named nephthea sp. Which already possessing the anti-inflammatory activity and extracted the silver Nanoparticles with petroleum ethers then the produced silver Nanoparticles of nephthea sp. having very potent anti-inflammatory activity which were estimated by analysis and molecular docking methods [93].

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9. Future prospects

AgNPs has potential applications in healthcare system and treating infectious diseases and it is emerging as remedies for large no of resistant bacteria infections along with it is known for its anti-inflammatory potential. Apart from it has numerous application in biological and research fields such as electrochemistry, biochemistry, nanoprism synthesis, garments, detergents and soap industry, involved in devising water purification system, and surgical instrument. Nowadays Ag-NPs opened new era as it has used in artificial implants which decreeing dependency on antibiotics. Studies have been revealed that Ag-NPs have novel potential in development of new pharmaceutical dosage forms and AgNPs cures inflammation of bladder which tremendous application in healthcare systems. AgNPs useful in animal models for detection of biosensors [94]. A reliable mechanism responsible for the impressive biological activity of AgNPs is considered to be a key factor in future research. Wide scope to aware control the release of silver and improving the stability of AgNPs used in medical and mechanical devices.

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10. Concslusion

Over the past few decades, nanoparticles of noble metals such as silver exhibited significantly distinct physical, chemical and biological properties from their bulk counterparts. Current chapter specifically encounters synthesis, characterization, and bio-applications of silver nanoparticles, with special emphasis on anticancer, antimicrobial activity and its mechanisms. Green chemistry is being exploited for developing silver nanoparticles. Several methods utilized to create silver nanoparticles utilizing plant extracts as reducing or capping agents. Current chapter represents different methods of preparation silver nanoparticles and application of these nanoparticles in different fields.

Acknowledgments

The authors are thankful to Department of Pharmaceutics Sant Gajanan Maharaj College of Pharmacy Mahagaon and Trustees of Sant Gajanan Maharaj College of Pharmacy Mahagaon for providing required guidance and support for completion of this work.

Conflict of interest

The authors declare no conflict of interest.

Notes/thanks/other declarations

Special thanks to Shivtej for continuous support throughout the work.

Abbreviations

AgNP&#;sSilver Nano ParticlesNPsNanoparticlesnmnanometerAgNO3Silver NitratePVPpolyvinyl pyrrolidonePEGpoly ethylene glycolPMAApoly methacrylic acidSPRsurface plasmon resonanceROSReactive oxygen species

A review on biosynthesis of silver nanoparticles and their ...

In general, metallic nanoparticles are produced by two methods, i.e. &#;bottom-up&#; (buildup of a material from the bottom: atom by atom, molecule by molecule or cluster by cluster) and &#;top-down&#; (slicing or successive cutting of a bulk material to get nano-sized particle) [1]. The &#;bottom-up&#; approach is usually a superior choice for the nanoparticles preparation involving a homogeneous system wherein catalysts (for instance, reducing agent and enzymes) synthesize nanostructures that are controlled by the catalyst itself. However, the &#;top-down&#; approach generally works with the material in its bulk form, and the size reduction to nanoscale is achieved by specialized ablations, for instance thermal decomposition, mechanical grinding, etching, cutting, and sputtering. The main demerit of the top-down approach is the surface structural defects. Such defects have significant impact on the physical features and surface chemistry of metallic nanoparticles. Several methodologies are available for the synthesis of Ag NPs namely, chemical methods [26,27,28,29]; physical methods [30,31,32] and biological methods [1, 10, 11]. Chemical method of synthesis can be subdivided into chemical reduction, electrochemical, irradiation-assisted chemical and pyrolysis methods [33]. Ag NPs synthesis in solution requires metal precursor, reducing agents and stabilizing or capping agent. Commonly used reducing agents are ascorbic acid, alcohol, borohydride, sodium citrate and hydrazine compounds. Sotiriou and Pratsinis [28] have shown that the Ag NPs supported on nanostructured SiO2 were obtained by flame aerosol technology, which allows close control of silver content and size. Also, silver/silica nanoparticles with relatively narrow size distribution were obtained by flame spray pyrolysis [29]. However, physical methods do not require lethal and highly reactive chemicals and generally have a fast processing time. These methods include arc-discharge [31], physical vapor condensation [30], energy ball milling method [34] and direct current magnetron sputtering [32]. Physical methods have another advantage over chemical methods in that the Ag NPs have a narrow size distribution [32], while the main demerits are consumption of high energy [32]. Thus, biological synthesis of Ag NPs from herbal extract and/or microorganisms has appeared as an alternative approach as these routes have several advantages over the chemical and physical methods of synthesis. It is also a well-established fact that these routes are simple, cost-effective, eco-friendly and easily scaled up for high yields and or production [1,2,3]. Biosynthesis of metal and metal oxide nanoparticles using biological agents such as bacteria, fungi, yeast, plant and algal extracts has gained popularity in the area of nanotechnology [1,2,3, 5, 6, 10, 11].

Plants and their parts contain carbohydrates, fats, proteins, nucleic acids, pigments and several types of secondary metabolites which act as reducing agents to produce nanoparticles from metal salts without producing any toxic by-product. The details have been provided in Table 1. Similarly, biomolecules such as enzymes, proteins and bio-surfactants present in microorganisms serve as reducing agents. For instance, in many bacterial strains, bio-surfactants are used as capping and/or stabilizing agents (Table 2).

Table 1 Plant-mediated synthesis of silver nanoparticles

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Table 2 Bio-surfactants and or stabilizing agents used during synthesis of silver nanoparticles from various bacterial stains

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Extracellular synthesis of Ag NPs comprises of the trapping of metal ions on the outer surface of the cells and reducing them in the presence of enzymes or biomolecules, while intracellular synthesis occurs inside the microbial cells. It has been suggested that the extracellular synthesis of nanoparticles is cheap, favors large-scale production and requires simpler downstream processing. Thus, the extracellular method for the synthesis of nanoparticles is preferable [164] in comparison to the intracellular method. Ganesh Babu and Gunasekaran [165] and Kalimuthu et al. [166] have demonstrated that the intracellular synthesis requires additional steps for instance, ultrasound treatment or reactions with suitable detergents to release the synthesized silver nanoparticles. Further, the rate of biosynthesis of Ag NPs and their stability is a significant part in industrial production. Therefore, a proper monitoring of reaction conditions is also important (Fig. 1).

Fig. 1

Biosynthesis of silver nanoparticles and their optimization techniques

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From bacteria

In recent years, the potential of biosynthesis of Ag NPs using bacteria has been realized [15, 153, 156,157,158,159]. For instance, Pseudomonas stutzeri AG259&#;isolated from silver mine was used to produce Ag NPs inside the cells [167]. In addition, several bacterial strains (gram negative as well as gram positive) namely A. calcoaceticus, B. amyloliquefaciens, B. flexus, B. megaterium and S. aureus have been used for both extra- and intracellular biosynthesis of Ag NPs [168,169,170,171,172,173,174]. These Ag NPs are spherical, disk, cuboidal, hexagonal and triangular in shape. They have been fabricated using culture supernatant, aqueous cell-free extract or cells (Table 3). Saifuddin et al. [14] have demonstrated an extracellular biosynthesis of Ag NPs (&#; 5&#;50 nm) using a combination of culture supernatant of B. subtilis and microwave irradiation in water. Shahverdi et al. [15] have reported rapid biosynthesis of Ag NPs (within 5 min) using the culture supernatants of K. pneumonia, E. coli and Enterobacter cloacae. Saravanan et al. [172] have also reported an extracellular synthesis of Ag NPs using B. megaterium cultured supernatant, within minutes in presence of aqueous solutions of Ag+ ions.

Table 3 Bacteria-mediated synthesis of silver nanoparticles

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Rapid synthesis of Ag NPs has been achieved by the interaction of a bacterial strain S-27, belonging to Bacillus flexus group and 1 mM AgNO3 in aqueous medium [173]. The colourless supernatant solution turned yellow and finally brown. Its UV&#;vis spectrum exhibited a sharp peak at 420 nm due to the surface plasmon resonance (SPR) of silver nanoparticles. Anisotropic nanoparticles of 12 and 65 nm size were stable in the dark for 5 months at room temperature although their slow degradation cannot be prevented. They were crystalline with a face centered cubic structure. These nanoparticles were found to be effective against multidrug resistant gram positive and gram negative bacteria. The colour intensity and rate of interaction depend on the concentration of the reacting components.

Das et al. [174] have reported extracellular biosynthesis of Ag NPs from the Bacillus strain (CS11). The interaction of 1 mM AgNO3 with the bacteria at room temperature yielded nanoparticles within 24 h which showed a peak at 450 nm in UV&#;vis spectrum. Their size from TEM analysis was found to range between 42 and 92 nm (Table 3).

From fungi

Biosynthesis of Ag NPs from both pathogenic and nonpathogenic fungi has been investigated extensively [10, 164, 213,214,215] (Table 4). It has been reported that silver ions are reduced extracellularly in the presence of fungi to generate stable Ag NPs in water [214, 216].

Table 4 Fungus-mediated synthesis of silver nanoparticles

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Syed et al. [224] have also reported the extracellular synthesis of Ag NPs from thermophilic fungus Humicola sp. All manipulations were done in aqueous medium at room temperature. Mycelia were suspended in 100 mL of 1 mM AgNO3 solution in an Erlenmeyer flask at 50 °C and the mixture was left in a shaker for 96 h at pH 9 and monitored for any change in colour. The solution showed a change in colour from yellow to brown due to the formation of Ag NPs [222]. It is a simple process for the extracellular synthesis of Ag NPs from Humicola sp. TEM micrograph showed nicely dispersed nanoparticles mainly of spherical shape ranging between 5 and 25 nm. They are crystalline with a face centered cubic structure [236]. IR spectrum of Ag NPs in the suspension showed peaks at and  cm&#;1 assigned to amide I and amide II bands of protein corresponding to &#;C=O and N&#;H stretches. Owaid et al. [237] have reported the biosynthesis of Ag NPs from yellow exotic oysters mushroom, Pleurotus cornucopiae var. citrinopileatus. The dried basidiocarps were powdered, boiled in water and the supernatant was freeze dried. Different concentrations of hot water extract of this lyophilized powder were mixed with 1 mM AgNO3 at 25 °C and incubated for 24, 48 and 72 h. Change in colour from yellow to yellowish brown exhibited an absorption peak at 420 and 450 nm in UV&#;vis region which is the characteristic of spherical silver nanoparticles. The width of the absorption peak suggests the polydispersed nature of nanoparticles [221]. IR spectrum of Ag NPs exhibited absorption peaks at , , , , , , and 611 cm&#;1 for different groups. Although, authors have indicated the presence of polysaccharide and protein in the mushroom they have ignored their stretching frequencies in the IR spectrum. However, the peak at has been assigned to υ (OH) of carboxylic acid and those at and  cm&#;1 have been attributed to unsaturated aldehydes. The other peaks below  cm&#;1 are due to unsaturated alkaloids. The field emission scanning electron and high-resolution transmission electron micrograph suggested that the Ag NPs are spherical with average size ranging between 20 and 30 nm.

Very recently, Al-Bahrani et al. [230] reported biogenic synthesis of Ag NPs from tree oyster mushroom Pleurotus ostreatus. Dried aqueous extract of mushroom (1&#;6 mg/mL) and 1 mM AgNO3 were mixed and incubated in the dark for 6&#;40 h. The colour change from pale yellow to dark brownish yellow indicated the formation of silver nanoparticles. The UV&#;vis spectrum showed a sharp and broad absorption band at 420 nm. They are polydispersed nanoparticles of 10&#;40 nm with an average size of 28 nm. Several fungi namely, Aspergillus flavus, A. fumigates, Fusarium oxysporum, Fusarium acuminatum, F. culmorum, F. solani, Metarhizium anisopliae, Phoma glomerate, Phytophthora infestans, Trichoderma viride, Verticillium sp. have been used for both extra- and intracellular biosynthesis of Ag NPs [10, 164, 216,217,218,219, 222]. These nanoparticles are of various sizes and shapes (Table 4).

From plants

Plant related parts such as leaves, stems, roots, shoots, flowers, barks, seeds and their metabolites have been successfully used for the efficient biosynthesis [1, 238] of nanoparticles (Fig. 1). Very recently, Beg et al. [128] have reported green synthesis of Ag NPs from seed extract of Pongamia pinnata. The formation of nanoparticles was confirmed by an absorption max at 439 nm. The well dispersed nanoparticles with an average size of 16.4 nm had zeta potential equal to &#; 23.7 mV which supports dispersion and stability. Interaction of Ag NPs with human serum albumin was investigated and showed negligible change in α helics. In a very recent publication Karatoprak et al. [137] have reported green synthesis of Ag NPs from the medicinal plant extract Pelargonium endlicherianum. The plant containing gallic acid, apocyanin and quercetin act as reducing agents to produce silver nanoparticles. Phytomediated synthesis of spherical Ag NPs from Sambucus nigra fruit extract has been reported by Moldovan et al. [144]. XRD analysis showed them to be crystalline. The in vivo antioxidant activity was investigated against Wistar rats which showed promising activity. It suggests that functionalization of Ag NPs with natural phytochemicals may protect the cell proteins from ROS production. Ag NPs have also been synthesized from aqueous leaf extract of Artocapus altilis. They were moderately antimicrobial and antioxidant. Thalictrum foliolosum root extract mediated Ag NPs synthesis has been confirmed on the basis of the appearance of a sharp peak at 420 nm in UV&#;vis region of the spectrum [239]. The monodispersed spherical nanoparticle of 15&#;30 nm had face centered cubic geometry. Shape and size dependent controlled synthesis of Ag NPs from Aloe vera plant extract and their antimicrobial efficiency has been reported by Logaranjan et al. [35]. The UV&#;vis peak at 420 nm confirmed the formation of silver nanoparticles. After microwave irradiation of the sample, Ag NPs of 5&#;50 nm with octahedral geometry was obtained. Nearly two to fourfold antibacterial activity of Ag NPs was observed compared to commonly available antibiotic drugs. Biosynthesis of Ag NPs from the aqueous extract of Piper longum fruit extract has been also achieved [240]. The nanoparticles were spherical in shape with an average particle size of 46 nm determined by SEM and dynamic light scattering (DLS) analyser. The polyphenols present in the extract are believed to act as a stabilizer of silver nanoparticles. The fruit extract and the stabilized nanoparticles showed antioxidant properties in vitro. The nanoparticles were found to be more potent against pathogenic bacteria than the flower extract of P. longum. Ag NPs have been fabricated from leaf extract of Ceropegia thwaitesii and formation was confirmed from absorption of SPR at 430 nm. The nanoparticles of nearly 100 nm diameter were crystalline in nature [139]. Plant extract of Ocimum tenuiflorum, Solanum tricobatum, Syzygium cumini, Centella asiatica and Citrus sinensis have been used to synthesize Ag NPs of different sizes in colloidal form [249]. The size of all nanoparticles was found to be 22&#;65 nm. They were all stable and well dispersed in solution. Niraimathi and co-workers [140] have reported biosynthesis of Ag NPs from aqueous extract of Alternanthera sessilis and showed that the extract contains alkaloids, tannins, ascorbic acid, carbohydrates and proteins which serve as reducing as well as capping agents. Biomolecules in the extract also acted as stabilizers for silver nanoparticles. Ag NPs from seed powder extract of Artocarpus heterophyllus have been synthesized [138]. The morphology and crystalline phase of the nanoparticles were determined by SEM, TEM and SAED, EDAX and IR spectroscopy. They were found to be irregular in shape. The extract was found to contain amino acids, amides etc. which acted as reducing agents for AgNO3 to produce silver nanoparticles. The quantity of phenols, anthocyanins and benzoic acid were determined in the berry juices and were responsible for the transformation of silver ions to Ag NPs [241]. UV&#;vis spectra displayed an absorbance peak at 486 nm for lingonberry and 520 nm for cranberry containing silver nanoparticles. Since the two absorption peaks are different they cannot be assigned only to Ag NPs but also partly to different quantities of the reducing chemicals present in the juices. However, the spectra indicated the presence of polydispersed silver nanoparticles. Puiso et al. [241] have proposed that due to irradiation of water by UV rays, strong oxidants and reductants as photolysis products are formed. They reduce silver ions to Ag NPs or silver oxide. The photolysis products may produce oxidant and reductant but it depends upon the quantum of radiation and exposure time which may not be enough to produce a sufficient quantity of redox chemicals to reduce Ag+ to Ag NPs or Ag2O. This hypothesis is conceptually incorrect because Ag2O cannot be formed as it requires a very strong oxidizing agent. On the other hand, AgNO3 itself is slowly reduced in water, but in the presence of reducing agents the reaction proceeds at a rapid rate. The SPR is dependent on the size, shape and agglomeration of Ag NPs which is reflected from the UV&#;vis spectra [242]. Mock et al. [243] have found different scattered colors in hyperspectral microscopic images which are mainly due to the different shape and size of silver nanoparticle in the colloidal solution. The blue, green, yellow and red colors have been attributed to spherical, pentagonal, round-triangle and triangle shapes, respectively.

Zaheer and Rafiuddin [12] have reported the synthesis of Ag NPs using oxalic acid as reducing agent and mistook it as green synthesis. Formation of nanoparticles was confirmed by a change in color of the solution which showed an absorption peak at 425 nm (Fig. 2a) in the UV&#;visible region. It was also noted that a scattered silver film was formed on the wall of the container that shines and reflects light (Fig. 2b) which is the characteristic of monodispersed spherical Ag NPs [244, 245]. Since the size of nanoparticles varies between 7 and 19 nm the silver film is not uniform. It is different from regular silver mirror due to irregular shape and size of nanoparticles (Fig. 2c). Actually, very small size nanoparticles can be obtained when AgNO3 is exposed to a reducing agent for a longer duration of time [246]. The kinetics and mechanism proposed for the formation of Ag NPs by oxalic acid is not convincing [12] because oxalic acid in no case can produce CO2 unless it reacts with any carbonate salt or heated at a very high temperature. The authors [12] have proposed following reactions to prove that the colour of Ag NPs in solution is due to Ag 2+4 formation that absorbs at 425 nm (Scheme 1). The formation of Ag 2+4 is highly improbable even if the above reaction is kinetically very fast. Also, the stabilization of Ag 2+4 is questionable (Scheme 1). This hypothesis of Ag 2+4 formation is beyond imagination and does not carry any experimental evidence in its support. Absorbance of Ag NPs in solution varies between 400 and 445 nm depending on the nature of reducing agent used for their fabrication. The SPR band in UV&#;vis spectrum is due to electron oscillation around the surface of nanoparticles. The reduction process is instantaneous and no further spectral change occurs after 60 min. Indicating the completion of redox process. Ag NPs are circular, triangular, hexagonal and polydispersed at 70 °C. The EDAX and XRD spectra support each other.

Fig. 2

a UV&#;visible spectra of yellow color silver solution. b and c SEM images of the self-assembled silver nanoparticle mirror like illumination on the walls of the glass. Reaction conditions: [Ag+] = 20.0 × 10&#;4 mol dm&#;3; [oxalic acid] = 4.0 × 10&#;4 mol dm&#;3; [CTAB] = 10.0 × 10&#;4 mol dm&#;3; temperature = 30 °C [12]

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Scheme 1

Reduction of Ag+ ions by oxalic acid [12]

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Synthesis of Ag NPs from aqueous extract of Cleistanthus collinus and their characterization by UV&#;vis, FTIR, SEM, TEM and XRD has been reported by Kanipandian et al. [247]. The crystalline Ag NPs of 20&#;40 nm showed significant free radical scavenging capacity. Tippayawat et al. [27] have reported a green and facile synthesis of Ag NPs from Aloe vera plant extract. They were characterized by UV&#;vis, SEM, TEM and XRD. Fabrication of Ag NPs was confirmed on the basis of the appearance of a sharp peak at 420 nm in UV&#;vis region of the spectrum. In addition, they have reported that the reaction time and temperature markedly influence the fabrication of silver nanostructures. Ag NPs were spherical in shape and particle size ranged from 70.70 ± 22 to 192.02 ± 53 nm. Their size changes with time and temperature of the reaction mixture used during fabrication (Fig. 3).

Fig. 3

SEM images of silver nanoparticles were obtained at a 100 °C for 6 h, b 150 °C for 6 h, c 200 °C for 6 h, d 100 °C for 12 h, e 150 °C for 12 h and f 200 °C for 12 h [36]

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Green synthesis of Ag NPs from Boerhaavia diffusa plant extract has been reported by Vijay Kumar et al. [136] where the extract acted as both the reducing as well as capping agent. The colloidal solution of Ag NPs showed an absorption maximum at 418 nm in the UV&#;vis spectrum. The XRD and TEM analyses revealed a face centered cubic structure with an average particle size of 25 nm. Ag NPs of 5&#;60 nm have been synthesized from Dryopteris crassirhizoma rhizome extract in presence of sunlight/LED in 30 min [235]. XRD studies showed face centered cubic structure of silver nanoparticles.

Green synthesis of Ag NPs using 1 mM aqueous AgNO3 and the leaf extract of Musa balbisiana (banana), Azadirachta indica (neem) and Ocimum tenuiflorum (black tulsi) has been done [248]. They were characterized by UV&#;vis, SEM, TEM, DLS, EDS and FTIR spectroscopy. They were found to accelerate the germination rate of Vigna radiata (Moong Bean) and Cicer arietinum (Chickpea). It is therefore, believed that Ag NPs are not toxic to such crops at germination level. Stable and capped Ag NPs from aqueous fruit extract of Syzygium alternifolium of 5&#;68 nm have been synthesized [92]. Nearly 12.7% of silver was detected from EDAX. The polydispersed spherical nanoparticles were capped and stabilized by the phenols and proteins present in the fruit extract. Biosynthesis of Ag NPs from methanolic leaf extract of Leptadenia reticulate has been done [142]. They were crystalline, face centred and spherical particles of 50&#;70 nm. They exhibited antibacterial activity and radical scavenging activity. Purple sweet potato (Ipomoea batatas L.) root extract has been exploited to synthesize Ag NPs [143]. Organic components in the extract acted both as reducing and capping agents. Ag NPs have shown remarkable antibacterial activity against four clinical and four aquatic pathogens. Sweet potato root extract is known to contain glycoalkaloids, mucin, dioscin, choline, polyphenols and anthocyanins which function as antioxidant, free radical scavenger, antibacterial agent and reducing agents. In presence of Ag NPs these functions are further enhanced.

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