A review on green synthesis of silver nanoparticles and their applications

Abstract

Development of reliable and eco-accommodating methods for the synthesis of nanoparticles is a vital step in the field of nanotechnology. Silver nanoparticles are important because of their exceptional chemical, physical, and biological properties, and hence applications. In the last decade, numerous efforts were made to develop green methods of synthesis to avoid the hazardous byproducts. This review describes the methods of green synthesis for Ag-NPs and their numerous applications. It also describes the comparison of efficient synthesis methods via green routes over physical and chemical methods, which provide strong evidence for the selection of suitable method for the synthesis of Ag-NPs.

Keywords:

• Green synthesis
• silver nanoparticles
• plant extracts
• extracellular synthesis
• intracellular synthesis
• applications

Introduction

Nanotechnology is referred to the term for manufacture, portrayal, manipulation, and application of structures by controlling shape and size at nanoscale (Sarsar et al. 2013). The field of nanotechnology is the most dynamic region of research in material sciences and the synthesis of nanoparticles (NPs) is picking up significantly throughout the world. NPs show totally novel or enhanced properties taking into account particular characteristics, i.e., size (1–100 nm), shape, and structure (Jahn 1999; Slawson et al. 1992; Nalwa 1999). NPs can be categorized broadly as inorganic and organic NPs. Inorganic NPs incorporate semi-conductor NPs (like ZnO, ZnS, CdS), metallic NPs (like Au, Ag, Cu, Al), and magnetic NPs (like Co, Fe, Ni), while organic NPs incorporate carbon NPs (like fullerenes, quantum dots, carbon nanotubes). There is a growing enthusiasm for Gold and Ag (noble metal) NPs as they furnish superior characteristics with useful flexibility (Vadlapudi and Kaladhar 2014). Ag-NPs have a substantial surface zone which results into noteworthy biochemical reactivity, catalytic activity, and atomic behavior compared with bigger particles having same chemical composition (Xu et al. 2006).

The formation of Ag-NPs has received significant interest because of their potential applications in catalysis (Kamat 2002), plasmonics (Maier et al. 2001), optoelectronics (Boncheva et al. 2002), biological sensors (Mirkin et al. 1996; Han et al. 2001), antimicrobial activities (Savithramma et al. 2011; Rai et al. 2009), DNA sequencing (Cao et al. 2001), Surface-Enhanced Raman Scattering (SERS) (Matejka et al. 1992), climate change and contamination control (Shan et al. 2009), clean water technology (Savage and Diallo 2005), energy generation (Zäch et al. 2006), information storage (Caruthers et al. 2007), and biomedical applications (Hullmann 2007). The formation of NPs has provided us remarkable developments in the field of nanotechnology by demonstrating its potential from the last decade (Samberg et al. 2010).

“Top-down” and “Bottom-up” are the two approaches for synthesis of NPs as shown in Table 1. In top-down approach, suitable bulk material splits into fine particles by size reduction with different techniques i.e., Pulse laser ablation, evaporation–condensation, ball milling, pulse wire discharge method etc. In bottom-up approach, NPs can be synthesized using chemical and biological methods by self-assembly phenomenon of atoms to new nuclei which grow into a particle of nanoscale. In top-down approach, evaporation–condensation is the most general method for synthesis of metal NPs (Daniel and Astruc 2004; Swihart 2003). In this technique the foundation material, inside a boat, is placed at centered in furnace and is vaporized into a carrier gas. Fullerene, PbS, Au and Ag NPs have already been synthesized by using evaporation-condensation technique. The tube furnace used in this method has various drawbacks as it occupies a substantial space and munches a lot of energy while raising temperature around the source material, and it similarly entails a lot of time to succeed thermal stability (Hurst et al. 2006; Elghanian et al. 1997). In addition, an average tube furnace requires pre-heating time of several minutes to achieve steady working temperature as well as power more than several kilowatts. One of the greatest limitations in this technique is the defects in the surface structure of the product where as physical properties of NPs are dependent on the structure of surface. In general, whatever the technique is followed, it is by and large presumed that physical methods are being used as a calibration tool and NP generator for long-term experiments for inward breath toxicity studies (Tran and Le 2013).

Table 1. Flow chart describing the techniques for synthesis of Ag-NPs.

Synthesis of nanoparticles
Bottom-up approach		Top-down approach
Green methods	Chemical methods	Physical methods
• Using bacteria• Using fungi• Using plant and their extracts• Using yeast• Using enzymes and biomolecules• Using microorganism	• Chemical reduction• Sonochemical• Microemulsion• Photochemical• Electrochemical• Pyrolysis• Microwave• Solvothermal• Coprecipition	• Pulsed laser ablation• Evaporation–condensation• Arc discharge• Spray Pyrolysis• Ball milling• Vapour and gas phase• Pulse wire discharge• Lithography
Non-toxic	Toxic

In bottom-up approach, chemical reduction is the most general method for the synthesis of Ag-NPs (Chitsazi et al. 2016; Wang et al. 2005; Guzmán et al. 2009). Various organic and inorganic reducing agents in aqueous or non-aqueous solutions are used for the reduction of Ag ions, for example, poly-ethylene glycol block copolymers, sodium citrate, Tollen’s reagent, Ascorbate, essential hydrogen, N,N-dimethyl formamide (DMF), and sodium borohydride (NaBH₄) (Tran and Le 2013; Guzmán et al. 2009; Chou and Ren 2000). Capping agents are additionally used for size stabilization of the NPs. One of the greatest advantages of this method is that a substantial amount of NPs can be synthesized in a short period of time. During this sort of synthesis, chemicals used are toxic and prompted non-ecofriendly byproducts. This is the reason that leads to biosynthesis of NPs by means of green route that does not use toxic chemicals, and henceforth demonstrating to turn into a developing wanton need to develop environment friendly process. Therefore, the development of green synthesis of Ag-NPs is advancing as a key branch of nanotechnology where the use of biological entities like plant extract or plant biomass, microorganisms for the generation of NPs could be an alternative to chemical and physical methods in an eco-friendly way (Reddy et al. 2012). The advancement of green synthesis over physical and chemical methods are environment friendly, cost-effective, and easily scaled up for vast scale synthesis of NPs, while high-temperature, energy, pressure, and harmful chemicals are not required for green synthesis (Ahmed et al. 2016b). Hence, this review describes the green-inspired synthesis of Ag-NPs that can provide advantage over the physical and chemical methods.

Green synthesis

The conventional methods for the production of NPs are expensive, toxic, and non-environment friendly. To overcome these problems, researchers have found the precise green routes, i.e., the naturally occurring sources and their products that can be used for the synthesis of NPs. Green synthesis can be categorized as: (a) utilization of microorganisms like fungi, yeasts (eukaryotes), bacteria, and actinomycetes (prokaryotes), (b) use of plants and plant extracts (c) use of templates like membranes, viruses DNA, and diatoms. The green synthesis via bacteria, fungi, plants, and plant extracts are described in the further sections.

Synthesis of Ag-NPs by using bacteria

Inorganic materials are produced by bacteria either extra or intracellular. This makes them potential biofactories for the formulation of noble metal NPs like Gold and Ag, as shown in Figure 1. Ag-NPs are known to be biocompatible but some bacteria are known to be Ag resistant (Slawson et al. 1992). Therefore, these bacteria can aggregate Ag on the cell walls, hence recommending their utilization in industrial recovery of Ag from ore materials (Pooley 1982). Initially, Klaus et al. (1999) reported that, Ag-NPs were synthesized by using Ag resistant bacterial strains Pseudomonas stutzeri AG259. These cells accumulate Ag-NPs in large amounts upto 200 nm. Ag-NPs were synthesized by Shivaji et al. (2011) using culture supernatants of psychrophilic bacteria. Kalimuthu et al. (2008) illustrated the synthesis of Ag-NPs by Bacillus licheniformis, where the aqueous solution of AgNO₃ added to the biomass of B. licheniformis, the color change from whitish-yellow to brown indicates the formation of Ag-NPs with the size range of 50 nm and were stabilized by enzyme nitrate. Ag-NPs were also synthesized by Nanda and Saravanan (2009) using culture supernatants of Staphylococcus aureus. However, for quick synthesis of Ag-NPs, the culture supernatants of various bacteria from Enterobacteriaceae can be used.

Figure 1. Schematic diagram for synthesis of Ag-NPs by using bacteria.

Samadi et al. (2009) studied that significant results were observed when Ag-NPs were synthesized by using bacteria Proteus mirabilis PTCC 1710. The extracellular and intracellular synthesis can be advanced through different kinds of broth used during incubation of bacteria. This selection of bacteria makes green synthesis flexible, reasonable, and a suitable method for large-scale synthesis. Photosynthesis is a kind of green synthesis in which we study the effect of various visible-light irradiations on the formation of Ag-NPs from Ag nitrate using the culture supernatant of Klebsiella pneumonia. Experimental results by Mokhtari et al. showed that liquid mixing process affects the Ag-NPs formation by visible light irradiation in size range of 1–6 nm. Shahverdi et al. (Lee 1996; Shehata and Marr 1971) studied that Ag-NPs were also produced by the reduction of aqueous Ag ions through various culture supernatants of bacteria, i.e., Enterobacter cloacae (Enterbacteriaceae), Escherichia coli and Klebsiella pneumonia. The synthesis rate is much faster, i.e., Ag-NPs were formed within 5 minutes of the Ag ions coming into contact with the cell filtrate (Shahverdi et al. 2007).

Besides the advantages, it is necessary to point out that bacteria kept on growing after the formation of Ag-NPs. Except this, the main disadvantage of utilizing bacteria as nanofactories is the slow synthesis rate and the limited number of sizes and shapes obtain as compare to conventional methods. Therefore, fungi based nanofactories and chemical reaction including plant and plant extracts based materials were investigated for Ag-NPs synthesis (Kharissova et al. 2013). Similarly, many other bacteria which can be used for the synthesis of Ag-NPs are shown in Table 2.

Table 2. Green synthesis of Ag-NPs using bacteria.

Bacteria	Precursor	Intracellular/extracellular	Size	Morphology	References
Cyanobacteria Spirulina platensis and actinobacteria Streptomyces spp. 211A	AgNO3	Extracellular	7–15	–	(Tsibakhashvil et al. 2010)
Aeromonas sp. THG-FG1.2	AgNO3		8–16	Face Centered Cubic (FCC), spherical	(Singh et al. 2016b)
Serratia nematodiphila	AgNO3	Extracellular	10–31	Crystalline and spherical	(Malarkodi et al. 2013)
Pseudomonas putida NCIM 2650	AgNO3	Extracellular	70	Spherical	(Thamilselvi and Radha 2013)
Escherichia coli DH5α	AgNO3	Extracellular	10–100	Spherical	(Ghorbani 2013)
Lactobacillus strains	AgNO3	–	15–500	Cluster triangular, hexagonal and crystalline	(Nair and Pradeep 2002)
Lactobacillus casei subsp. casei	AgNO3	–	25–50	Spherical	(Korbekandi et al. 2012)
Nocardiopsis sp.MBRC-1	AgNO3	–	45 ± 0.15	Spherical	(Manivasagan et al. 2013)
Pseudomonas stutzeri AG259	AgNO3	–	35–46 and upto 200	Crystalline, hexagonal and equilateral triangle	(Haefeli et al. 1984)
Shewanella oneidensis	AgNO3	Extracellular	4 ± 1.5	Spherical	(Suresh et al. 2010)
Penicillium glabrum (MTCC 1985)	AgNO3	Extracellular	26–32	Spherical	(Nanda and Majeed 2014)
Bacillus strain CS 11	AgNO3	Extracellular	45 ± 0.15	FCC, spherical	(Das et al. 2014)
Actinobacteria	AgNO3	Intracellular	5–50	Spherical	(Suman et al., 2014)
Bacillus sp.	AgNO3	Intracellular	5–15	Crystalline	(Pugazhenthiran et al. 2009)
Vibrio alginolyticus	AgNO3	Extra and Intracellular	50–100	Crystalline and spherical	(Rajeshkumar et al. 2013)
Marine Ochrobactrum sp.	AgNO3	Intracellular	38–85	Spherical	(Thomas et al. 2014)
Exiguobacterium mexicanum	Ag NO3	Extracellular	5–40	–	(Padman et al. 2014)
Endosymbiotic Bacterium	AgNO3	Extracellular	10–60	Cubic, spherical, hexagonal, crystalline, oval	(Syed et al. 2016)
Bacillus subtilis (MTCC441)	AgNO3	Extracellular	10–100	Spherical	(Venkatesan et al. 2013)
Lactobacillus spp.	AgNO3	Extra and intracellular	2–20	Spherical	(Ranganath et al. 2012)
Novosphingobium sp.HG-C3	AgNO3	Extracellular	8–25	Spherical and crystalline	(Du et al. 2016)
Kinneretia THG-SQ14	AgNO3	Extracellular	15–20	Mono-disperse, FCC, spherical	(Singh et al. 2016a)
Bacillus methylotrophicus		Extracellular	10–30	Spherical	(Wang et al. 2015)
S1–S10	AgNO3	Intra/Extracellular	25–30	–	(Nanda et al. 2011)
Rhodococcus spp.	AgNO3	Intracellular	5–50	Spherical	(Otari et al. 2015)

Synthesis of Ag-NPs by using fungi

Fungi have potential for the synthesis of metallic NPs due to metal bioaccumulation capacity and their tolerance, high binding capacity, and intracellular uptake like bacteria that are easy to handle in a research facility as compare to bacteria (Sastry et al. 2003). Fungi can be used through different methods for the synthesis of NPs, in which fungi secrete enormous enzymes which are utilized to reduce AgNO₃ solution (Mandal et al. 2006). A schematic representation is shown in Figure 2. The extracellular synthesis of Ag-NPs by utilizing F. oxysporum and its antibacterial effect on textile fabrics is studied by Durán et al. (2007). Vigneshwaran et al. (2007) reported that mono-disperse Ag-NPs can be synthesized by using fungus Aspergillus flavus and average size of the NPs observed in the range of 8.92 ± 1.61 is measured by Transmission Electron Microscopy (TEM). The extracellular synthesis of Ag-NPs using fungus Cladosporium cladosporioides is observed by Balaji et al. and the size of NPs is observed by TEM in the range of 10–100 nm (Balaji et al. 2009). In another method, Kathiresan et al. (2009) illustrated in vitro synthesis of Ag-NPs using AgNO₃ as a substrate and Penicillium fellutanum isolated from coastal mangrove sediment. Ahmad et al. (2003) studied that aqueous Ag ions when exposed to the Fusarium oxysporum are reduced in solution by an enzymatic process, prompting the formation of highly stable Ag hydrosol. The NPs are in the size range 5–15 nm and are stabilized in solution by protein-secreted fungus. The extracellular synthesis of mono-dispersed Ag-NPs is achieved by Bhainsa and D’Souza (2006) using Aspergillus fumigatus at quick synthesis rate. In another method, spherical Ag-NPs are synthesized by Li et al. (2011) using Aspergillus terreus with an average size of 1–20 nm.

Figure 2. Schematic diagram for synthesis of Ag-NPs by using fungi.

Mukherjee et al. (2001) reported that mono-dispersed Ag-NPs are synthesized by utilizing fungus Verticillium by green approach. The exposure of the fungal biomass to aqueous solution of AgNO₃ resulted in the intracellular reduction of the metal ions; NPs are spherical in shape and size range up to 25 ± 12 nm. Ag-NPs are synthesized below the surface of the fungal cells as compared to bacteria with spherical, triangular to hexagonal shapes. The mechanism of NPs synthesis is, in fungi-based synthesis, NPs are formed on the surface of mycelia, not in solution. In first step, Ag + particles were adsorbed on the surface of the fungal cells due to the presence of electrostatic interaction between negatively charged carboxylate groups in enzymes and positively charged Ag ions. The Ag particles are reduced by the enzymes present in cell walls, prompting the development of Ag nuclei. The Ag-NPs were also synthesized by Vahabi et al. (2011) using fungus Trichoderma reesei and in the size range of 5–50 nm.

The shifting from bacteria to fungi for producing normal nanofactories offers the advantages of more straightforward downstream processing, treatment of the biomass and secrete much higher amounts of proteins, which tends to drastically increase the profitability of this synthetic approach as compared with bacteria. The extracellular formulation of Ag-NPs by using eukaryotic systems, i.e., fungi was studied by Ahmad et al. (2003) and also demonstrated that secreted enzymes are responsible in the reduction. Prior to this, all the fungi-based green syntheses are intracellular. Extracellular synthesis is useful as formulated NPs would not bind to biomass (Duran et al. 2007; Balaji et al. 2009). As compared with the other classes of microorganisms, their eco-friendliness and straightforwardness during taking care, lead to increase the utilization of fungi in green synthesis, i.e., fungus like white rot fungus is non-pathogenic which promote the large-scale synthesis of Ag-NPs (Vigneshwaran et al. 2006). Another supporting point using this method is the reaction rate. These investigations are clearly describing suitability and the potential of utilizing fungi for the large-scale synthesis of NPs as compare to bacteria. Recently, Naqvi et al. (2013) reported that Ag-NPs were synthesized using A. flavus fungi and to be combined with antibiotics to upgrade the biocidal effectiveness against multidrug-resistant bacteria. This study shows the efficiency of antibiotics combined with Ag-NPs. Other fungi which are used for synthesis are presented in Table 3.

Table 3. Green synthesis of Ag-NPs using fungi.

Fungi	Precursor	Intracellular/Extracellular	Size (nm)	Morphology	References
Humicola sp.	AgNO3	Extracellular	5–25	Spherical	(Syed et al. 2013)
Penicillium citrinum	AgNO3	Extracellular	109	Uniform spherical	(Honary et al. 2013)
Filamentous fungus Penicillium sp.	AgNO3	–	58.35 ± 17.88	–	(Hemath Naveen et al. 2010)
Endophytic fungus Penicillium sp.	AgNO3	Extracellular	25 and 30	Spherical	(Singh et al. 2014)
Endophytic bryophilous	AgNO3	Extracellular	25–50	Ellipsoidal	(Raudabaugh et al. 2013)
Aspergillus niger, Fusarium oxysporum and Alternaria solani	AgNO3	–	20	Spherical	(Ghazwani 2015)
Schizophyllum commune	AgNO3	Intracellular & Extracellular	51–93	Spherical	(Arun et al. 2014)
Trichoderma reesei	AgNO3	Extracellular	5–50	Random	(Vahabi et al. 2011)
Fusarium semitectum	AgNO3	Extracellular	1–50	Ellipsoid and polydispersed spherical	(Shelar and Chavan 2014)
Aspergillus niger	AgNO3	–	1–20	Polydispersed spherical	(Sagar and Ashok 2012)
Trichoderma harzianum	AgNO3	–	34.77	Ellipsoid and spherical	(Shelar and Chavan 2015)
Fusarium acuminatum	AgNO3	Extracellular	13	Spherical	(Ingle et al. 2008)
Penicillium fellutanum	AgNO3	Extracellular	5–25	Spherical	(Kathiresan et al. 2009)
Endophytic fungus Aspergillus clavatus	AgNO3	Extracellular	10–25	Hexagonal and polydispersed spherical	(Verma et al. 2010)
Pestalotia sp.	AgNO3	Extracellular	12.40	Polydispersed and spherical	(Raheman et al. 2011)
Alternaria alternata	AgNO3	Extracellular	32.5	Polydispersed and spherical	(Gajbhiye et al. 2009)
Fusarium semitectum	AgNO3	Extracellular	10–60	Crystalline and spherical	(Basavaraja et al. 2008)
Phoma glomerata	AgNO3	Extracellular	60–80	Spherical	(Birla et al. 2009)
Trichoderma viride	AgNO3	Extracellular	5–40	Spherical	(Fayaz et al. 2010)

Synthesis of ag-NPs by using plant and plant extracts

Gardea-Torresdey et al. (2003) illustrated that the first approach of using plants for the synthesis of metallic NPs was done by using Alfalfa sprouts, which was the first description about the synthesis of Ag-NPs using living plant system. Alfalfa roots have the ability to absorb Ag from agar medium and voyage them into shoots of plant in same oxidation state. In shoots, these Ag atoms arranged themselves to produce Ag-NPs. Ahmad and Sharma (2012) reported that Ag-NPs are synthesized by utilizing Ananas comosus (pineapple juice) as stabilizing as well as reducing agent and synthesized NPs were characterized by High Resolution Transmission Electron Microscopy (HRTEM), UV–Vis spectrometer, Energy Dispersive X-ray Spectroscopy (EDX), and Selected Area Diffraction (SAD). TEM micro-graphs represented the spherical NPs with an average diameter of 12 nm. Ag-NPs are synthesized by utilizing Argemone mexicana leaf extract as capping as well as reducing agent by adding to the aqueous solution of AgNO_3. The properties of NPs are analyzed by using UV–Vis spectrometer, X-Ray diffractometer (XRD), Scanning Electron Microscopy (SEM), and Fourier Transmission Infrared (FTIR) Spectrophotometer. Singh et al. (2010) showed that XRD and SEM revealed the average size of NPs as 30 nm. Gavhane et al. (2012) studied that Ag-NPs were synthesized by the reduction of aqueous AgNO₃ solution through the extract of Neem and Triphala and characteristics of NPs were analyzed by using EDX, nanoparticles tracking analysis (NTA), and TEM. NTA and TEM revealed the spherical particles size range of 43 nm and 59 nm.

Velmurugan et al. (2015) illustrated that Ag-NPs are synthesized by peanut shell extract and their characteristics and antifungal activity is compared with commercial Ag-NPs. UV–Vis spectra, XRD peaks, and FTIR confirmed that synthesized and commercial NPs are similar and HRTEM results indicate that NPs were mostly spherical and oval in shape with an average diameter up to 10–50 nm. In another method, spherical Ag-NPs were also synthesized by Roy et al. (2014) using the fruit extract of Malus domestica as capping agent with an average diameter of 20 nm. The formation of NPs is analyzed by UV–Vis spectroscopy, distinctive phases and morphology are confirmed by using XRD and TEM, and FTIR is used to identify the biomolecules which are responsible for reduction and stabilization of NPs. Kaviya et al. (2011) synthesized Ag-NPs by using Polyalthia longifolia leaf extract as reducing agent along with d-sorbital to enhance the stability of NPs. Ag-NPs were synthesized by Maqdoom et al. (2013) using the fruit extract of Papaya and are characterized by Absorption spectroscopy and FTIR. Rout et al. (2012) reported that spherical-shaped Ag-NPs were synthesized by using Ocimum sanctum leaf extract as stabilizing agent and characteristics of particles were studied by using UV–Vis spectrometer, SEM, and XRD. Awwad et al. (2013) studied that spherical Ag-NPs were also synthesized by using carbo leaf extract with an average particle size from 5 to 40 nm and characterized by using UV–Vis spectroscopy, atomic absorption spectroscopy (AAS), XRD, SEM, and FTIR. The UV–Vis spectra showed surface plasmon resonance (SPR) for Ag-NPs at 420 nm and XRD results demonstrated that Ag-NPs having face-centered cubic geometry and crystalline in shape.

Bar et al. (2009) represented that Ag-NPs were synthesized by reduction of aqueous AgNO₃ solution using latex of Jatropha curcas as capping agent. Udayasoorian et al. (2011) illustrated that Ag-NPs were also synthesized by using the leaf extract of Cassia auriculata as reducing as well as capping agent. Kasthuri et al. (2009) synthesized Ag-NPs by reduction of aqueous Ag + ions through leaf extract of Apiin as capping and reducing agent and TEM results showed average diameter of particles to be 21–39 nm. Shankar et al. (2003) represented the extracellular synthesis of Ag-NPs by Geranium leaf extract where AgNO₃ is added to it and the quick reduction of the Ag ions leaded to production of crystalline, stable Ag-NPs with size 40 nm. Stable and spherical Ag-NPs are synthesized by using Ficus benghalensis leaf extract with an average particle size 10–50 nm. The characteristics of synthesized NPs were studied by FTIR, SEM, Thermal Gravimetric Analysis (TGA), and XRD by Saware et al. (2014).

Nakkala et al. (2014) studied that Acorus calamus extract can be used as capping agent for the synthesis of Ag-NPs to evaluate its oxidation state, anticancer, and antibacterial effect. Kumar et al. (2014) reported that Ag-NPs are synthesized using the extracts of Boerhaavia diffusa, XRD and TEM results showed an average size 25 nm having face-centered cubic geometry with spherical shape. These NPs were used for antibacterial action against three fish bacteria, namely Pseudomonas fluorescens, Aeromonas hydrophila, and Flavobacterium. Krishnaraj et al. (2010) synthesized Ag-NPs by using the leaf extract of Acalypha indica. Dwivedi and Gopal (2010) reported that spherical Ag-NPs are synthesized by using obnoxious weed Chenopodium album with size range 10–30 nm as measured by TEM. In another method, synthesis of Ag-NPs is reported by Aldebasi et al. (2015) using an aqueous mixture of Ficus carica leaf extract. Ag-NPs are synthesized by Awwad et al. (2012) using the extract of Olea europaea and characterized by using SEM, XRD, and FTIR. The spherical Ag-NPs have been synthesized using the extract of Abutilon indicum and also studied their high antimicrobial activity against S. typhi, E. coli, S. aureus, and B. subtilis microorganism by Ashokkumar et al. (2015).

Awwad and Salem (2012) reported that mono-dispersed and spherical Ag-NPs were synthesized by using Mulberry leaves extract with average particle size of 20 nm. The characteristics of synthesized Ag-NPs are analyzed by UV–Vis spectroscopy, XRD and SEM as well as revealed their effective antibacterial activity towards Staphylococcus aureus and Shigella sp. Khalil et al. (2014) studied that Ag-NPs are synthesized by the reduction of AgNO₃ solution through olive leaf extract and these particles showed effective antibacterial activity against drug-resistant bacteria isolates. The characteristics of NPs are studied by using UV–Vis spectroscopy, XRD, TGA, and SEM, and results showed that NPs are mostly spherical with an average diameter of 20–25 nm. Alternanthera dentate leaf extract is used as a capping agent for green synthesis of Ag-NPs by Kumar et al. (2014). Thus, the use of plant extract in green synthesis has stimulated various investigations and studied till now. It was demonstrated that the formation of metal NPs using plant extract could be finished in the metal salt solution within short duration at room temperature depending upon the nature of plant extract. After the selection of the plant extract, the main affecting parameters are the concentration of the extract, temperature, metal salt, pH, and contact time (Mittal et al. 2013). In addition to the formation parameters, the principal issue is the selection of the plant from which the extract could be used. The benefits of using plants for the formation of NPs are that plants are easily accessible and safe to handle and have a large range of active agents that can advance the reduction of Ag ion. Mainly the plant parts like roots, latex, stem, seeds, and leaves are being used for NPs synthesis (Kharissova et al. 2013). The interesting point is the active agent presents in these parts, which makes the stabilization and reduction possible and plant extracts incorporate biomolecules which act both as reducing and stabilizing agent that produce stable and shape-controlled NPs. Main compounds which influence the reduction and capping of the NPs are biomolecules, i.e., terpenoids, polysaccharides, phenolics, alkaloids, flavones, amino acids, alcoholic compounds enzymes, and proteins. Similarly, chlorophyll pigments and quinal, methyl chavicol, linalool, caffeine, eugenol, ascorbic acid, theophylline, and other vitamins have also been investigated (Sharma et al. 2009; Bindhu and Umadevi 2013). Murugan et al. (2014) reported that Ag-NPs are synthesized by using Acacia leucophloea extract in size range upto 38–72 nm. Arokiyaraj et al. (2014) reported that, Ag-NPs were synthesized using Chrysanthemum indicum. L. and NPs within the size range 17–29 nm. Kumar et al. (Ashok 2012; Kumar et al. 2013) have shown that, Ag-NPs were synthesized by using the leaf extract of Parthenium hysterophorus, Premna herbacea, and added to the aqueous solution of AgNO₃. Recently, Rodríguez-León et al. (2013) reported that Ag-NPs are also synthesized using the Rumex hymenosepalus extract. The other plant and plant extracts used for the synthesis of Ag-NPs are given in Table 4.

Table 4. Green synthesis of Ag-NPs using plant and plant extracts.

Plants/plant extracts	Precursor	Reducing and capping agent	Size (nm)	Structure/shape	References
Helicteres isora	AgNO3	Root extract	30–40	Crystalline and spherical	(Bhakya et al. 2015)
C. olitorus Linn and I.batatas Lam	AgNO3	Leaves extract	37.9 & 67.3	Crystalline	(Meva et al. 2016)
Rheum palmatum	AgNO3	Root extract	121 ± 2	Cubic, spherical and hexagonal	(Arokiyaraj et al. 2016)
Excoecaria agallocha	AgNO3	Leaves extract	20	Crystalline, hexagonal and spherical	(Bhuvaneswari et al. 2016)
Banana	AgNO3	Peel extract	23.7	Crystalline and spherical	(Ibrahim 2015)
Eucalyptus globulus	AgNO3	Leaves extract	1.9–4.3 and 5–25	Spherical	(Ali et al. 2015)
Oranges and pineapples	AgNO3	Fruit extract	Depends upon fruit extract	Depends upon fruit extract	(Hyllested et al. 2015)
Solanum nigrum andclitoria ternatea	AgNO3	Leaves extract	23	Spherical	(Jassal et al. 2016)
Cranberry	AgNO3	Powder extract	2.8 ± 2.1, 1.4 ± 0.8, 8.6 ± 2.5	Spherical	(Ashour et al. 2015)
Phyllanthus niruri	AgNO3	Leaves extract	30–60	Crystalline FCC and spherical	(Suresh et al. 2015)
Bryophyllum and Asiatic Pennywort	AgNO3	Leaves extract	18–21	Crystalline FCC and spherical	(Saikia et al. 2015)
Zingiber officinale rhizome	AgNO3	Broth extract	3.1	Crystalline and spherical	(Shalaby et al. 2015)
Tagetes erecta	AgNO3	Flower broth	10–90	Irregular, hexagonal and spherical	(Padalia et al. 2015)
Orange	AgNO3	Peel extract	91	Spherical	(Awad et al. 2014)
Piper betle	AgNO3	Leaves extract	–	–	(Prabha et al. 2014)
Justica adhatoda	AgNO3	Leaves extract	11–20	Smooth and spherical	(Kudle et al. 2014)
Eucalyptus leucoxylon	AgNO3	Leaves extract	50	FCC and spherical	(Rahimi-Nasrabadi et al. 2014)
Oak	AgNO3	Fruit extract	40	Cubic and spherical	(Heydari and Rashidipour 2015)
Chrysanthemum indicum L	AgNO3	Flower extract	37.71–71.99	Crystalline FCC and spherical	(Arokiyaraj et al. 2014)
Asclepias curassavica	AgNO3	Leaves extract	75–95	Spherical	(G.S.O.S.N. 2014)
Dextran	AgNO3	Dextran solution	50–70	Spherical	(Hussain et al. 2014)
Alstonia scholaris	AgNO3	Bark extract	50	Spherical	(Shetty et al. 2014)
Piper nigrum	AgNO3	Leaves extract	7–50 and 9–30	Crystalline and spherical	(Paulkumar et al. 2014)
Achillea bieberstennii	AgNO3	Flower extract	12 ± 2	Hexagonal, pentagonal and spherical	(Baharara et al. 2014)
Ocimum tenuiforum, Azadirachta indica and Musa balbisiana	AgNO3	Leaves extract	Up to 200	Cubical, spherical and triangular	(Banerjee et al. 2014)
Vitex negundo	AgNO3	Leaves extract	60	Spherical	(Kathireswari et al. 2014)
Pithophora oedogonia	AgNO3	Algal extract	34.03	Hexagonal and cubical	(Sinha et al. 2015)
Sida acuta and Artemisia annua	AgNO3	Leaves extract	–	–	(Johnsona et al. 2014)
Datura metel	AgNO3	Leaves extract	5–50	Spherical	(Kumar Ojha et al. 2013)
Partheniumhysterophorus L.	AgNO3	Leaves extract	20–50	Roughly spherical	(Thombre et al. 2013)
Rumex hymenosepalus	AgNO3	Root extract and plant extract	2–40	Hexagonal and FCC	(Rodríguez-León et al. 2013)
Tecoma stans	AgNO3	Leaves extract	15	FCC and spherical	(Arunkumar et al. 2013)
Lens culinaris	AgNO3	Seed exudates	13	Crystalline and spherical	(Shams et al. 2013)
Citrus sinensis, Solanumtricobatum, Cuminiasiatica and Syzygium cumini	AgNO3	Plant powders	41, 42. 52 and 53	Crystalline and irregular	(Logeswari et al. 2013)
Dalbergia sissoo	AgNO3	Leaves extract	5-55	Crystalline and spherical	(Singh et al. 2012)
Nelumbo nucifera	AgNO3	Leaves extract	45	Decahedral, truncated triangles, spherical and triangle	(Santhoshkumar et al. 2011)
Macrotyloma uniflorum	AgNO3	Seed extract	12	Anisotropic, FCC and nearly spherical	(Vidhu et al. 2011)
Desmodium triflorum	AgNO3	Plant Broth	10	Spherical	(Ahmad et al. 2011)
Melia azedarach	AgNO3	Seed extract	–	–	(Shams et al. 2014)
Calliandra haematocephala	AgNO3	Leaves extract	70	Spherical and FCC	(Raja et al. 2015)
Trilobata	AgNO3	Leaves extract	–	–	(Billacura and Mimbesa 2015)
Pongam pinnata L. Pierre	AgNO3	Leaves biomass	38	Spherical	(Raut et al. 2010)
Achyranthes aspera L.	AgNO3	Leaves extract	1.0 ± 18.3	Spherical	(Gude et al. 2013)
Nerium oleander	AgNO3	Leaves extract	380–420	–	(Subbaiya et al. 2014)
Premna serratifolia L.	AgNO3	Leaves extract	22.97	Cubic	(Paul et al. 2015)
Catharanthus roseus	AgNO3	Root extract	35–55	Crystalline FCC and spherical	(Rajagopal et al. 2015)
Calotropis procera	AgNO3	Latex serum extract	12.33	Spherical	(Mohamed et al. 2014)
Aloe vera	AgNO3	Leaves extract	70	Spherical, rectangular, cubical and triangular	(Medda et al. 2015)
Allium cepa	AgNO3	Extract	33.6	Spherical	(Saxena et al. 2010)
Garlic	AgNO3	Extract	4–6	–	(Von White et al. 2012)
Prunus armeniaca	AgNO3	Fruit extract	Less than 20	Crystalline and spherical	(Dauthal and Mukhopadhyay 2013)
Peach gum	AgNO3	Peach gum powder	23.56 ± 7.87	FCC	(Yang et al. 2015)
Psidium guajava	AgNO3	Leaves extract	26 ± 5	Crystalline and spherical	(Raghunandan et al. 2011)
Solanum lycopersicum	AgNO3	Fruit extract	10	Spherical	(Umadevi et al. 2013)
Solanum tuberosum	AgNO3	Potato infusion	10–12	Crystalline, FCC and spherical	(Roy et al. 2015)
Juglans Regia L.	AgNO3	Leaves extract	10–50	Quasi spherical	(Korbekandi et al. 2013)
Citrus limon	AgNO3	Limon extract	Less than 50	Spheroidal and spherical	(Prathna et al. 2011)
Chenopodium album	AgNO3	Leaves extract	10–30	Quasi spherical	(Dwivedi and Gopal 2010)
Honey	AgNO3	Honey solution	4	Crystalline and spherical	(Philip 2010b)
Mentha piperita	AgNO3	Leaves extract	5–30	Spherical	(Parashar et al. 2009)
Henna	AgNO3	Leaves extract	50	Spherical	(Daniel et al. 2013)
Hibiscusrosa sinensis	AgNO3	Extract	14	Prism or spherical	(Philip 2010a)
Tea	AgNO3	Leaves extract	20	Prism or spherical	(Sun et al. 2014)
Albizia lebbeck	AgNO3	Plant extract	–	Roughly spherical	(Parvathy et al. 2014)
Syzygium cumini	AgNO3	Bark extract	20–60	Spherical	(Prasad and Swamy 2013)
Tribulus terrestris	AgNO3	Fruit extract	16–28	Spherical	(Gopinath et al. 2012)
Ziziphora tenuior	AgNO3	Leaves extract	8–40	Spherical	(Sadeghi and Gholamhoseinpoor 2015)
Melia dubia	AgNO3	Leaves extract	35	Spherical	(Kathiravan et al. 2014)
Thevetia peruviana	AgNO3	Latex extract	10–30	Spherical	(Rupiasih et al. 2015)
Vitex negundo	AgNO3	Leaves extract	5 and 10–30	FCC and spherical	(Zargar et al. 2011)
Brassica rapa	AgNO3	Leaves extract	16.4	–	(Narayanan and Park 2014)
Vitis vinifera	AgNO3	Fruit extract	30–40	–	(Gnanajobitha et al. 2013)
Musa paradisiacal	AgNO3	Peel extract	20	–	(Bankar et al. 2010)
Eclipta prostrate	AgNO3	Leaves extract	35–60	Hexagons, triangles and pentagons	(Rajakumar and Rahuman 2011)
Cuminum cyminum	AgNO3	Seeds powder	12	Smooth surface and spherical	(Kudle et al. 2012)
Securinega Leucopyrus	AgNO3	Leaves and fruit extract	11–20	Spherical, oval and smooth	(Donda et al. 2013)
Lantana camara	AgNO3	Fruit extract	12.55–12.99	Spherical	(Sivakumar et al. 2012)
Pistacia atlantica	AgNO3	Seeds extract	10–50	Spherical	(Sadeghi et al. 2015)
Carica papaya	AgNO3	Fruit extract	15	Hexagonal and cubic	(Jain et al. 2009)
Ficus carica	AgNO3	Leaves extract	13	–	(Geetha et al. 2014)
Memecylon edule	AgNO3	Leaves extract	20–50	Hexagonal, circular, triangular	(Elavazhagan and Arunachalam 2011)
Swietenia mahogany	AgNO3	Leaves extract	50	–	(Mondal et al. 2011)
Trachyspermum ammi	AgNO3	Seed extracts	87, 99.8	–	(Vijayaraghavan et al. 2012)
Olea europaea	AgNO3	Seed extracts	34	Crystalline	(Sadeghi 2014)
Prunus japonica (Rosaceae)	AgNO3	Leaves extract	26	Hexagonal, spherical, crystalline and irregular	(Saravanakumar et al. 2016)
Terminalia arjuna	AgNO3	Bark extract	2–100	Spherical	(Ahmed et al. 2016a)
Catharanthus roseus	AgNO3	Leaves extract	20	Crystalline, FCC and spherical	(Al-Shmgani et al. 2016)
Turbinaria ornata (Turner)	AgNO3	Seaweed aqueous extract	20–32	Spherical and crystalline	(Deepak et al. 2016)
Althaea officinalis radix	AgNO3	Hydroalcoholic extract		Polydispersed and spherical	(Korbekandi et al. 2016)
Quercus brantii	AgNO3	Leaves hydroalcoholic extract	6	Polydispersed and spherical	(Korbekandi et al. 2015)

It is investigated that green synthesis using plant and plant extracts appears to be faster than other microorganisms, such as bacteria and fungi. The use of plant and plant extracts in green synthesis has drawn attention because of its rapid growth, providing single step technique, economical protocol, non-pathogenic, and eco-friendly for NPs synthesis. The schematic diagram for the green synthesis of Ag-NPs using plant or plant extract is shown in Figure 3.

Figure 3. Schematic diagram for synthesis of Ag-NPs by using plan/plant extracts.

Applications of Ag-NPs

Ag-NPs have numerous antimicrobial and antifungal applications. Ag-NPs have been broadly used as antibacterial coat in therapeutic applications, such as cardiovascular implants, wound dressings, catheters, orthopedic implants, dental composites, nano-biosensing, and agriculture engineering (He et al. 2016). The detailed description of the number of applications is described further.

Cardiovascular implants

First cardiovascular device coated with Ag element was prosthetic silicone heart valve to diminish the occurrence of endocarditic (Grunkemeier et al. 2006). This utilization of Ag was proposed to avoid bacterial contamination on the silicone valve and reduce the inflammation reaction of heart. It is found that Ag causes allergic reaction, inhibits normal fibroblast function and leads to paravalvular outflow in patient during Ag heart valve testing in clinical trials. Consequently, efforts transformed into incorporating Ag-NPs into medical device as a potential for giving safe, non-toxic, and antibacterial coating. Another advancement of nanocomposites with Ag-NPs and diamond-like carbon as a surface coating for heart valves and stents showed antithrombogenic and antibacterial properties (Andara et al. 2006). The incorporation of nanostructure materials into backbone of polymers in polymeric heart valves enhances biocompatibility, resistance to calcification, and toughness (Ghanbari et al. 2009).

Catheters

Catheters used in the hospital setting have a high penchant for contamination, which can lead to undesirable complications. However, Ag-NPs have been used for decreasing biofilm development on catheters. Polyurethane catheters have been modified with a coat of Ag-NPs to make powerful antibacterial catheters. Ag-NPs coated catheters can productively reduce bacteria up to 72 h in animal models, and these are non-toxic (Roe et al. 2008; Hussain et al. 2006; Chou et al. 2008). Clinical pilot study reporting the avoidance of Catheter-Associated Ventriculitis (CAV) found no frequency of CAV, and all cerebrospinal fluid cultures were negative in 19 patients who have received Ag-NP-coated catheter (Lackner et al. 2008).

Wound dressings

Ag injury dressings have been used to clinically treat different injuries, such as burns, chronic ulcers, pemphigus, and toxic epidermal necrolysis (Chaloupka et al. 2010). Ag-NPs used in wound dressing appreciably diminished injury therapeutic time by a standard of 3.35 days while growing bacterial clearance from contaminated injuries with no unfriendly impacts as compare to standard Ag Sulfadiazine and gauze dressing (Huang et al. 2007). Compared with conventional 1% Ag sulfadiazine cream or plain petrolatum gauze, Ag-NPs used in wound dressings can enhance therapeutic in superficial burn wounds and made no difference in therapeutic profound burn wounds, quicken re-epithelialization although, no new tissue formation, i.e., angiogenesis and expansion (Chen et al. 2006). Chitosan-Ag-NPs used in wound dressing exhibited essentially enhanced injury therapeutic compared with 1% Ag sulfadiazine alongside the deposition of less Ag, which may worse the occurrence of argyria or skin staining (Lu et al. 2008). Chitin-Ag-NPs used in wound dressings had an antibacterial potential for wound therapeutic applications (Singh and Singh 2014; Madhumathi et al. 2010).

Orthopedic and orthodontic implants and fixations

Implant associated and joint substitution bacterial contaminations are high at 1.0–4.0% and are the most genuine complexities in orthopedic surgery in light of the fact that they are hard to treat and results in increased morbidity and drastically worse results (Alt et al. 2004; Zheng et al. 2010; Belt et al. 2001; Liu et al. 2012). Ag-NPs have been incorporated into plain poly bone reinforce, utilized for safe connection of joint prostheses hip and knee substitution surgery, as an approach to decrease bacterial resistance.

Dentistry

Ag-NPs have been used in dental instruments and bandages. Incorporation of Ag-NPs into orthodontic adhesive can increase or maintain the shear bond strength of an orthodontic adhesive while expanding its resistance to bacteria (Akhavan et al. 2013). Ag-NPs into dental composites could decrease the microbial colonization of coating materials, improving antifungal proficiency (Magalhães et al. 2012). Ag-NPs joined into endodontic fillings showed an prolonged antibacterial impact against Streptococcus milleri, Staphylococcus aureus and Enterococcus faecalis (Lee et al. 2007).

Nanoparticles impregnated fabrics for clinical clothing

Ag-NPs could show high sturdiness to treated fabrics that lead to an increment in the strength of material capacities due to their high surface area to volume ratio and high surface energy. Ag-NPs have been used to produce towels, furniture materials, kitchen fabrics, self-cleaning, bed lines or reusable surgical gloves, veils, patient dresses and antibacterial injury dressings, defensive face covers, suits against biohazards, restorative items, ultrahydrophobic fabrics, sportswear and potential applications in the generation of profoundly water-repulsive materials. Beside this, the effect of Ag impregnation of surgical scour suits on surface bacterial pollution in veterinary clinic lowered bacterial colony counts as compare to polyester/cotton cleans. The outcomes demonstrated that Ag impregnation gave an impression of being successful in decreasing bacterial contamination of scours in veterinary healing facility (Freeman et al. 2012; Van Duyne et al. 2003).

Nano-biosensors

NPs are exceptional characters for biosensors as they can be detected by various methods, i.e., optic absorption fluorescence and electric conductivity. By utilizing SPR, the Ag-NPs attain very high sensitivity and measurements (Doria et al. 2012). The novel physicochemical properties of metals at nanoscale have prompted improvement of wide variety of biosensors, i.e., nanobiosensors for the purpose of disease diagnosis, monitoring malady pathogenesis or therapy monitoring, cell tracking, and nanoprobes in vivo detecting/imaging, and other nanotechnology-based gadget (Marchiol 2012).

Agricultural engineering

Nanosized lignocellulosic materials are obtained from harvests and trees which had opened-up another market for innovative and worth nanosized materials and items. These can be used in foods and other packaging development and transportation vehicle body structures. Nanofertilizer, nanopesticides incorporating nanoherbicides, nanocoating, and brilliant delivery system for plant nutrients are being utilized widely as a part of agribusiness with numerous production industries which contain 100–250 nm Ag-NPs that are more soluble in water, thereby increasing their activity (Prasad et al. 2014). Nanofertilizers have the capacity to synchronize the release of nutrient with their plant uptake, along these lines keeping away from nutrient losses and decreasing the risks of groundwater contamination. Nanofertilizers ought to discharge the nutrient on interest while keeping them from permanent changing into chemical/gaseous forms that cannot be absorbed by plants. This can be accomplished by averting nutrient from interacting with microorganisms, water, and soil, and liberating nutrients when they can be directly internalized by the plant (Prasad et al. 2010; Chaudhry et al. 2008).

Other applications

Ag-NPs are also used in the expanded field of nanotechnology in several consumer byproducts, i.e., water filters and sanitization system, deodorants, soaps, socks, food preservation, and room sprays, which expand business sector of Ag-NPs (Manjumeena et al. 2014; Yang et al. 2009; Chen and Schluesener 2008; Saha et al. 2009). Ag-NPs and their composites have greater catalytic activities in the area of dye reduction and their removal (Sharma et al. 2015). Many other fields where Ag-NPs have potential applications are summarized in Table 5.

Table 5. Potential applications of Ag-NPs.

Medical applications	• Dental cements	(Magalhães et al. 2012)
	• Healing of burns and wound care	(Chaloupka et al. 2010, Huang et al. 2007)
	• Skin therapy and crucial in cosmetics	(Kokura et al. 2010, Silver 2003)
	• Reconstructive orthopedic surgery and bone cements	(Caplan 2005, Shi et al. 2006)
	• Medical devices and plastic catheters	(Roe et al. 2008, Monteiro et al. 2009)
	• Target drug delivery	(Ahamed et al. 2010)
	• Medical imaging, biolabeling and detection	(Loo et al. 2005, Houk et al. 2009) (Alivisatos 2004)
	• Cancer therapy	(Boca et al. 2011)
	• Coating of hospital textiles such as face mask surgical	(Lu et al. 2008, Van Duyne et al. 2003)
	• gowns, coating of breath mask patent and ultrasonic detection	(Tran and Le 2013, Morley et al. 2007)
	• Coating of implants for joint replacement	(Alt et al. 2004, Zheng et al. 2010,)
	• Orthodontic and orthopedic fixations and implants	(Belt et al. 2001, Liu et al. 2012)
Environmental applications	• Air disinfection	(Yoon et al. 2008)
	• Drinking water purification	(Zhang 2013)
	• Biological wastewater and ground water disinfection	(Sheng and Liu 2011, Mpenyana-Monyatsi et al. 2012)
	• Surface disinfection	(Kumar et al. 2008)
	• Wastewater treatment	(Benn and Westerhoff 2008)
Consumer goods and personal care products	• Textiles, paints and sunscreen cosmetics. Toys and humidifiers, filters, kitchen utensilstoothpaste, washers systems, shampoo, Bedding, deodorants, and fabrics.	(Ahamed et al. 2010, Baker et al. 2005)
Food	• Nutraceutical, food safety and food packaging	(Ramos et al. 2014, Morones et al. 2005, Duncan 2011)
	• Biosensors for food analysis	(Pérez-López and Merkoçi 2011)
Electronic components and transportation	• Sensors, electrodes and integrated circuits	(Kotthaus et al. 1997, Hau et al. 2009, Fukuda et al. 2012)
	• Nano wires and high energy batteries.	(Jana et al. 2001, Jasinski et al. 1967)
Antibacterial activity	• Ag-NPs exhibits inhibitory activity against Gram positive, Gram negative, Pseudomonasaeruginoss, Bacillus cereus, Escherichia hermanii, Bacillus subtilis, Klebsiella pneumonia,agricultural plant pathogens, and antibiotic resistant bacteria.	(Prabha et al. 2014, Paulkumar et al. 2014, Sinha et al. 2015, Bhakya et al. 2015, Meva et al. 2016, Shalaby et al. 2015, Kumar Ojha et al. 2013, Saxena et al. 2012, Govarthanan et al. 2016)
Antimicrobial activity	• Ag-NPs have antimicrobial activity against S. epidermidis, P. fluorescens, Klebsiella Pneumonia, Pseudomonas aeruginosa, Pseudomonous sp., Gram positive, Gram negative, Salmonella typhi, R. arrhizus, and Proteus vulgaris, and multidrug resistant bacteria.	(Govarthanan et al. 2016, Hussain et al. 2014, Kumar Ojha et al. 2013, Logeswari et al. 2013, Shalaby et al. 2015, Shetty et al. 2014, Singh et al. 2016b)
Antiviral activity	• Ag-NPs exhibits antiviral activity against human immunodeficiency virus-1, Influenza virus,(HIV-1), Herpes simplex virus, HSV-2, Monkey pox virus, hepatitis B, HSV-1, and Respiratory syncytial virus.	(Ahmed et al. 2015, Baram-Pinto et al. 2009, Elechiguerra et al. 2005, Lara et al. 2010, Lu et al. 2008, Rogers et al. 2008, Sun et al. 2008)
Antifungal activity	• Ag-NPs have fungicidal and antifungal activity against Candida albicans, Candida krusei, Candida species, Candida glabrata, Trichophyton mentagrophytes, and Candida tropicalis.	(Coker et al. 2011, Gajbhiye et al. 2009, Kim et al. 2008, 2009, Manjumeen et al. 2014)

Toxicological limitations of silver nanoparticles

Silver nanoparticles are quickly developing their utilization in an extensive range of commercial products throughout the world. Ag-NPs are widely used in many applications, especially medical and biological applications. The living organisms are directly or indirectly exposed to NPs where question is raised about their toxicity. Therefore, there is always need to define the conditions for safe use of NPs in biological and clinical applications. But, still there is lack of authenticated information regarding exposure of ecological, animals and human to Ag-NPs and the potential risks concerning their short and long haul harmfulness toxic effects. An overview of the toxic effects of Ag-NPs is shown in Tables 6 and Kamat 2002.

Table 6. In-vitro toxicity effects of Ag-NPs.

Particles size (nm)	Dose	Concentration	Exposure time	Cell/organisms	Major outcomes	References
13.2 ± 4.72	0.5–8.0μg Ag/mL	0.5–8.0 μg Ag/mL	4–24 hours	Suspension cells (U937) and adhesive cells (HeLa)	• Cell death is dose dependent. • Ag-NPs exhibits significant toxicity toward the U937 and HeLa tumor cells.• Cytotoxicity was determined by change in cell viability.	(Kaba and Egorova 2015)
29.57	7.74 mg/l and1.16 mg/l	2.5–5 mg/l	48–72 hours	HaCat and HeLa cell lines	• Apoptotic cell population was significantly increase by increasing Concentration of Ag-NPs in HeLa and HaCat cell lines. • It is studied that Adenosine diphosphate (ADP):Adenosine triphosphate (ATP) ratios were increased than their associated controls.• At high concentration, huge variations inadenylate kinase (AK) activity was occurred.• Upon exposure of Ag-NPs HeLa cells exhibits higher sensitivity as compare to HeCaT cells.	(Mukherjee et al. 2012)
1.98–64.9	1.73 × 10^4/cm^3, 1.27 × 10^5/cm^3 1.32 × 10^6particles/cm^3	p < 0.1	4 hours	Sprague–Dawley rat	• Higher concentration of Ag-NPs decreased the cell viability and mitochondrial function as rising lactate dehydrogenase (LDH) leakage. • Due to exposure of Ag-Nps no significant organ weight was changed.• Doses of Ag-Nps caused no significant health effect.	(Ji et al. 2007)
10, 40, and 75	5–50 μg/mL	5–50 μg/mL	4 and 24 hours	In the lung cells of human	• Viability of human lung cells is effected byexposure of Ag-NPs. • Intracellular metal release due to the difference in intracellular localization and cellular uptake are explained by the difference in ecotoxicity.	(Gliga et al. 2014)
15 and 100	10–50μg/ml	10–50 μg/ml	24 hours	BRL 3A rat liver cells	• Ag-NPs indicate depletion of reduced glutathione (GSH), reduction of mitochondrial membrane potential and generation of reactive oxygenspecies (ROS). • At higher concentration of Ag-NPs membrane was damaged.	(Hussain et al. 2005)
61.2 ± 33.9	25–75 mg l^−1	25–75 mg l^−1	24 hours	Kidney cells of mammalian	• Ag-NPs induced genotoxicity in porcine kidney (PK15) cells.• Deoxyribonucleic acid (DNA) damage like DNA–DNA/DNA–protein cross links oxidatively, single and double strand becomes an cause of alkaline damages upon the exposure of Ag-Nps. • Dose dependent DNA damage.	(Milić et al. 2015)
22.18	1.91 × 107particles/cm^3	1.91 × 10^7	6 hours/day for 14 days	Male C57BL/6 mice	• Potential immunotoxicity and neurotoxicity	(Lee et al. 2010)
254 ± 27	10.7 μg/mL	0.0345–345 μg/mL	24 hours	In the range of Rainbow Trout cell Lines (RTG, RTL-W1, and RTH-149) also with primary Hepatocytes	• Ag-NPs exhibits toxic effect on fresh waterenvironments. • Specific effects of Ag-NPs were indicated by using lysosomal damage as an indicator.	(Connolly et al. 2015)
15	8.75 μg/ml or21.3 μg/ml	10 μg/ml and above	48 hours	Dependent Toxicity stem cell line Reduced (C 18-4) of Mouse spermatogonial	• Increased membrane leakage and reducedmitochondrial function.	(Braydich-Stolle et al. 2005)
18	1.73 × 104/cm^3–1.27 × 105/cm^3 1.32 × 106 particles/cm^3	1.323 × 10^6 particles/cm^3, 61 μg/m^3	6 hours/day during 90 days	Sprague–Dawley rat	• Enhanced liver inflammation and bile ducthyperplasia. Reduced the alveolar inflammation and tidal volume.	(Sung et al. 2008)
20	278 ng/cm^2	6μg/mL	24 hours	Lung cells	• No significant induction of proinflammatorymediators and cytotoxicity was observed by applying realistic dose of Ag-NPs.	(Herzog et al. 2013)

Table 7. In-vivo toxicity effects of Ag-NPs.

Particles size (nm)	Dose	Concentration	Exposure time	Cell/organisms	Major outcomes	References
2.5–150	0.7 × 10^6, 1.4 × 10^6 and 2.9 × 10^6	32 × 10^6 particles/cm^3, 61 μg/m^3	90 days	Bone marrow of male and female rat	• No significant organ weight change and bone marrow cytotoxicity was indicated in male and female rats. • Dose dependent MNPECs number was increased in male rat and no detection was found treatment related to enhanced number of MNPCEs in female rats	(Kim et al. 2011)
100	2.8 μg/ml	20–4000 μg/ml	7 days	Rat ear and BALB/c3T3 cell lines	• In the permeability of biological barrierssignificant changes was occurred.	(Zou et al. 2014)
35 and ≤100	0.625, 1.25, 2.5, 5, 7.5, 10, 15, 20, and 25 mg/L	50 μg/ml	24–72 hours	Fathead minnow	• In embryos morphological abnormalities and high mortality are mostly edema	(Scown et al. 2010)
˜180	0, 50, 100, 250, 500, and 1000 mg/kg/day	5.50, 3.56, 2.87, 2.10, 11.28 μg/g wet weight	2 weeks	Rat hepatic cytochrome P450(CYP)	• To inhibit CYP enzymes activities.Loss of drug efficacy for patients due to unwanted changes in plasma drug levels.	(Kulthong et al. 2012)
81	25–84 μg L^−1	>72 μg L^−1	48 hours	Zebrafish (Danio rerio)	• At higher concentration all fishes were dead.	(Bilberg et al. 2012)
10	50 and 100 μg/ml	p < 0.05	2 times/day for 10 minutes during 5 days	Fruit fly (Drosophila melanogaster)	• Apoptosis in the larvae, heat shock protein 70, induction of oxidative stress and DNA damage markers.	(Siddique et al. 2009)
20, 25, 35, 50, and 80	0.34–1.7 μgml^−1	1.7–0.000544 μg/mL	14 days	Porcine skin	• After 14 days intercellular and intra consecutive cellular epidermal days edema.	(Samberg et al. 2010)
18–19	0.63 × 10^6 particles/cm^3, 49 mg/m^3, 1.43 × 10^6 particles/cm^3, 133 mg/m^3 and 3.03 × 10^6 particles/cm^3, 515 mg/m^3	1.32 × 10^6 particles/cm^3, 61 μg/m^3	For 13 weeks 6 hours/day, 5 days/week.	Lungs and liver in Sprague–Dawley rats.	• Dose dependent bile-duct hyperplasia was increased in the liver of female and male rat.• In the lungs of female and male macrophage accumulation, chronic alveolar inflammation was reported.	(Sung et al. 2009)
243.8 ± 176.7	121.1 ± 7.6 pg/mL, 47.4 ± 1.8 pg/mL and 32.2 ± 2.8 pg/mL, 8.2 ± 1.9 pg/mL, and 2.2 ± 0.4 pg/mL	125 μg/kg, 250 μg/kg, and 500 μg/kg	7–28 days	Male mice	• Adverse effects of Ag-NPs on mice and due to disturbance in homeostasis of body may cause many inflammatory diseases such as mesothelioma, pneumo coniosis, and emphysema.	(Park et al. 2011)
25	100, 500, and 1000 mg/kg	100, 500, and 1000 mg/kg	24 hours	Adult-male C57BL/6N mice	• Generate neurotoxicity by producing free radical induced oxidative stress and also by changing gene expression generate neurotoxicity and apoptosis.	(Rahman et al. 2009)

Conclusions

In summary, it is concluded that during the last decade many efforts have been made for the development of green synthesis. Green synthesis gives headway over chemical and physical methods as it is cost-effective, eco-accommodating and effectively scaled up for large-scale synthesis. Nature has exquisite and inventive methods for making the most competent miniaturized functional materials. An increasing awareness towards green chemistry and utilization of green route for production of metal NPs, especially Ag-NPs led a desire to develop eco-friendly methods. Organisms ranging from straightforward bacteria to highly complex eukaryotes can be utilized for the synthesis of NPs with desired size and shape. However, the development of the micro-organisms and vast scale formulation residue are tricky compared with others. The low synthesis rate and limited number of size and shape distributions produced, oriented the study towards utilization of plants. For the production of Ag-NPs using plants can be advantages over other biological entities which can overcome the slow route of using microorganisms and sustain their culture which can lose their potential towards the production of NPs. Other advantages of synthesis from plant extracts are provision of hygienic working environment, health and environment shielding, lesser wastages and most stable products. Ag-NPs synthesized by green route have important aspects of nanotechnology through numerous applications. Ag-NPs have emerged in present and future era, with a variety of applications incorporating cardiovascular implants, dentistry, medicine, therapeutics, biosensors, agriculture, and many more.