Microchemical Journal 196 (2024) 109615

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Microchemical Journal
journal homepage: www.elsevier.com/locate/microc

Review Article

A comprehensive review on silver nanoparticles: Synthesis approaches,

characterization techniques, and recent pharmaceutical, environmental,
and antimicrobial applications
Galal Magdy a, *, Eman Aboelkassim a, Shymaa M. Abd Elhaleem b, Fathalla Belal b
a
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, P.O. Box 33511, Egypt
b
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, P.O. Box 35516, Egypt

A R T I C L E I N F O A B S T R A C T

Keywords: Recently, there has been a growing interest in metal nanoparticles, particularly silver nanoparticles (Ag-NPs),
Silver nanoparticles due to their distinct physicochemical, biological, and antimicrobial characteristics, making them a novel cate­
Fluorescent nanosensors gory of luminescence-based nanomaterials. Consequently, Ag-NPs have been proposed for various applications as
Synthesis
optical and electrochemical sensors for the quantification of different analytes in diverse matrices, including
Characterization
environmental, pharmaceutical, and food products. Additionally, there were reports of applications pertaining to
Applications
antimicrobial properties. The extensive utilization of Ag-NPs can be mostly attributed to their exceptional
luminescent properties, straightforward synthesis methods, cost-effective starting materials, heightened sensi­
tivity, ease of measurement, and remarkable chemical stability. Consequently, it is crucial to thoroughly examine
the associated impacts and potential applications of Ag-NPs. The novelty of this review pertains to its compre­
hensive coverage of diverse synthetic approaches employed for the production of Ag-NPs, as well as the char­
acterization techniques employed to analyze their properties. Furthermore, the review encompasses an
exploration of the applications of Ag-NPs in different fields, including pharmaceutical, environmental, and
antimicrobial, over the last five years (2018–2022). Finally, current challenges and future trends are also dis­
cussed, providing proof for distinct and substantial possibilities for new approaches focusing on Ag-NPs and
recommending the need for less toxic, economic, and rapid synthetic approaches. This review serves as a
comprehensive resource that can effectively support and propel future investigations and advancements in the
discipline, specifically pertaining to the utilization of comparable nanomaterials.

1. Introduction are permanently attractive to society,

unlike their macro-scaled counterparts. The variation in the physi­
Metallic nanoparticles (NPs) are a kind of nanomaterial with a size ochemical features of NPs can be attributed to the surface-to-volume
range of 1–100 nm and versatile forms based on variations in starting ratio [1].
materials and synthetic methods. Compared with all known NPs to date, Size and size distribution control is a significant task that often
metallic NPs (especially silver nanoparticles (Ag-NPs)) with remarkable happens due to a change in the synthesis methods, reducing agents, and
features involving surface plasmon resonance, thermal and electrical stabilizers. So far, several stabilizing and capping agents have been re­
conductivity, size-dependent optical properties, and catalytic activities ported for the surface-functionalization of Ag-NPs. In general, the

Abbreviations: Ag-NPs, Silver nanoparticles; FT-IR, Fourier Transform Infrared spectroscopy; ATR, Attenuated total reflection; XRD, X-ray Diffraction; XPS, X-ray
Photoelectron Spectroscopy; ESCA, Electron spectroscopy for chemical analysis; DLS, Dynamic Light Scattering; EM, Electron microscopy; TEM, Transmission
Electron Microscopy; SEM, Scanning Electron Microscopy; AFM, Atomic Force Microscopy; ELS, Electrophoretic light scattering; NSOM, Near-field scanning optical
microscopy; STM, Scanning tunneling microscopy; FCS, Fluorescence correlation spectroscopy; RS, Raman scattering; CD, Circular dichroism; NMR, Nuclear
magnetic resonance; SAXS, Small-angle X-ray scattering; FS, Fluorescence spectroscopy; SPR, Surface plasmon resonance; LSPR, Localized surface plasmon reso­
nance phenomenon; CL, Chemiluminescence; ECL, Electrochemiluminescence; GCE, Glassy carbon electrode; CV, Cyclic voltammetry; SERS, Surface-enhance­
d Raman scattering; SDS, Sodium dodecyl sulfate; β-CD, β-cyclodextrin; RLS, Resonance light scattering.
* Corresponding author.
E-mail address: [email protected] (G. Magdy).

https://doi.org/10.1016/j.microc.2023.109615
Received 24 June 2023; Received in revised form 3 November 2023; Accepted 4 November 2023
Available online 10 November 2023
0026-265X/© 2023 Elsevier B.V. All rights reserved.
G. Magdy et al. Microchemical Journal 196 (2024) 109615

fabrication of Ag-NPs involves several physical and chemical procedures responsible for diagnosis and treatment in the pathological region [16].
that can usually be classified as “top to bottom” or “bottom to up” ap­ Additionally, Ag-NPs possess effective catalytic action in numerous
proaches [2]. Recently, green synthetic routes were developed and uti­ applications, starting from fuel cells, structural ceramics, and photo­
lized to obtain Ag-NPs and bypass the production of hazardous catalysis up to solar cells. It was proved that growing particles of Ag-NPs
substances [3]. play a vital role as a catalyst over stable particles. Ag-NPs also react with
Due to their unique and tunable merits, Ag-NPs are currently being some harmful and toxic gases, such as carbon monoxide and nitrogen
employed for numerous applications, including wastewater treatment, oxide, to prevent the environmental pollution resulting from burning
catalytic activity, targeted drug delivery, and antimicrobial activity [4]. gasoline and coal [17].
Of these, the most popular application of Ag-NPs is the colorimetric and Recent literature reviews have been conducted on the topic of Ag-
fluorescent nanosensors due to their convenience, rapid detection abil­ NPs. Several studies have been conducted on the green synthesis of
ities, easy-to-use nature, and fast “turn on/off” spectral differ­ Ag-NPs [18–21], while others have focused on exploring the antibac­
entiation before and after interaction with target compounds [5,6]. terial applications of Ag-NPs [19,22,23]. Several other studies have
Remarkably, the colorimetric sensing performance of Ag-NPs is espe­ explored the environmental applications of Ag-NPs [20,24–26]. Never­
cially related to the quantum effect of NPs, the surface charges, elec­ theless, the recent synthetic methodologies, characterization tech­
tronic structures, and the stabilizing and capping agents. In contrast, niques, and potential applications of Ag-NPs were not emphasized.
fluorescent NPs generally rely on the interaction of the metal and fluo­ Accordingly, the main objective of this review was to offer a complete
rophore, which are referred to as “metal-enhanced fluorescence” [7]. perspective on the diverse methods of synthesis and characterization
Ag-NPs based analyses have been widely utilized for the potential esti­ techniques, as well as the current pharmaceutical and environmental
mation of a variety of drugs [8], metal ions [6,9], water pollutants [10], applications and the antimicrobial properties of Ag-NPs. Finally, this
proteins [11], enzymes [12], and deoxyribonucleic acid (DNA) [13]. study addresses the challenges and future prospects associated with Ag-
Moreover, Ag-NPs have an essential and influential role in medicine NPs.
for biosensing and bioimaging, along with anticancer and antibacterial
therapies. The effectiveness of silver ions and silver-based compounds is 2. Synthesis of Ag-NPs
great against microorganisms, including several species of bacteria [14].
Regarding this aspect of nano-silver, it is considered an ideal and in- Synthesis of Ag-NPs was reported to be performed using one of the
demand choice for several roles in the medical field. The nitrate form following approaches, either the “top to down” or “bottom to top” ap­
of silver is often used to induce an antimicrobial effect. It has been hy­ proaches [27] (Fig. 1).
pothesized that Ag-NPs can lead to cell lysis or inhibition of cell trans­ The main difference between the two approaches is that the “Top to
duction via several mechanisms of growth inhibition and cell lysis. Ag- down” approach is a destructive method that depends on the size
NPs are also applied as diagnostic and therapeutic agents for diseases, reduction of bulk materials, where Ag-NPs’ synthesis could be per­
mainly cancer [15]. After systemic administration of Ag-NPs, they are formed by different physical methods. While the “Bottom to top”
directed to specific sites in the body through conjugation with a suitable method is a constructive technique that depends on building up atoms
ligand that has a distinguishable and certain binding activity to the into particles in the nanoscale, which is performed by chemical or green
target cells and, therefore, raises the concentration of agents that are processes [28].

Fig. 1. Schematic diagram for different synthetic approaches of Ag-NPs.

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G. Magdy et al. Microchemical Journal 196 (2024) 109615

The synthesis of Ag-NPs could also be classified into three methods, fumigatus [76], and algae such as Gelidiella acerosa [77].
including physical, chemical, and green methods (Fig. 1). Plants have many constituents that could be used as reducing agents,
for example, flavonoids, alkaloids, saponins, phenolics, and tannins
2.1. Physical synthesis [78]. Many plants have been employed in the production of nano­
particles, such as cinnamon, aloe vera, and many other plants [79].
The synthesis of Ag-NPs could be performed by different physical Plants have numerous advantages that make them a better option for Ag-
methods, including mainly the evaporation–condensation technique and NPs’ synthesis than other methods, as they are less toxic, safer, and
laser ablation method [29]. available [15]. For instance, Magdy et al. [80] synthesized Ag-NPs using
In the evaporation–condensation technique, Ag-NPs are synthesized piper cubeba seed extract as a green reducing agent and used them as a
by converting the material of interest into a gas using a tube furnace, and fluorescent probe for the spectrofluorimetric determination of two
then the vapor is condensed, forming nuclei that grow readily into antimicrobial drugs: ornidazole and miconazole nitrate (Fig. 3).
nanoparticles [30,31]. The change in this process parameters has been Another example of green methods is irradiation-assisted synthesis,
found to have a significant effect on the size [32], concentration [33], which includes many techniques, such as microwave-mediated synthesis
and hence the yield of nanoparticles [34]. For example, the Ag-NPs and gamma radiation. For instance, well- crystallized Ag-NPs have been
synthesized by a small and flat plate heater accompanied by a local developed by microwave using glycerol and corn starch. The developed
heating area resulted in pure, spherical, and stable nanoparticles with Ag-NPs were highly stable and had diameters of 2.9–44 nm (Fig. 4) [81].
high concentration [35].
In the laser ablation method, pure Ag-NPs are synthesized in air or 3. Identification and characterization of Ag-NPs
solution without using any further reagents [36,37]. The properties of
Ag-NPs produced by laser ablation techniques are affected by many Investigation of the nature, size, shape, morphology, surface chem­
conditions, including laser wavelength, laser fluency, duration of irra­ istry, composition, stability, and dispersity of Ag-NPs is achieved using
diation, and finally, the liquid medium nature [38–42]. For instance, various analytical techniques to confirm and evaluate their formation.
Rafique et al. [43] developed spherical and crystalline Ag-NPs using Brief descriptions of basic techniques commonly performed for Ag-
laser ablation in deionized water, which confirmed that the nature of the NPs’ characterization and investigation are addressed and covered
laser could affect the properties of nanoparticles (Fig. 2). below.

3.1. Uv–vis spectroscopy

2.2. Chemical synthesis

UV–Vis spectroscopy is an extremely valuable and consistent

There are various approaches for the chemical synthesis of Ag-NPs,
approach for the initial characterization of the prepared Ag-NPs, which
such as chemical reduction [44–46], reverse micelle [47–49], electro­
is also used to display their synthesis and stability. It is considered the
chemical [50–52], and chemical vapor deposition [53–55]. The most
simplest way to confirm proficiency in the formation of nanoparticles.
commonly used method for producing Ag-NPs is chemical reduction
The spherical and smaller Ag-NPs are differentiated by narrow peaks at
[56], which is performed by the reduction of a silver precursor using
about 400 nm, whereas larger Ag-NPs are characterized by broad peaks
chemicals such as sodium borohydride and N,N-dimethyl formamide
at a longer wavelength. Finally, UV–Vis spectroscopy is regarded as
[57,58]. Although the yield of the chemical method is large and pro­
simple, fast, time-saving, sensitive, and selective for various types of NPs
duced in a short time, green methods are preferred since they are less
[82]. Al Masoud et al. [83] reported on Ag-NPs’ fabrication using Ginger
toxic, eco-friendly, and more economical [59].
extract. The UV–Vis spectrum demonstrated a significant absorption
band at 434 nm, which confirmed the formation of Ag-NPs (Fig. 5).
2.3. Green synthesis
3.2. Fourier Transform infrared (FT-IR) spectroscopy
In the last years, the synthesis of Ag-NPs using green methods has
dramatically increased because of their advantages like availability,
FT-IR is an approach established to measure the absorption of elec­
cost-effectiveness, energy efficiency, eco-friendliness, and low toxicity
tromagnetic radiation at wavelengths within the mid-infrared region
[21,59]. Such green methods include the use of microorganisms
(4000–400 cm− 1). The recorded spectra give information regarding the
[60–64], plants [65,66], and irradiation-assisted methods [67–72].
interactions and molecular structures as they determine the positions of
Nanoparticles have been synthesized using a variety of microor­
peaks according to the nature and strength of bonds and specific func­
ganisms, including bacteria such as Klebsiella pneumonia [73] and
tional groups [84]. The FT-IR spectral analysis indicates the presence of
Escherichia coli [74], fungi such as Aspergillus flavus [75] and Aspergillus
several functional groups involving amide (–CO-NH2), carbonyl (–CO),
and hydroxyl (–OH), which are responsible for the capping, reduction,
and stability of Ag-NPs [85]. Recently, attenuated total reflection (ATR)-
FTIR spectroscopy has been developed to investigate the chemical fea­
tures on the polymer surface. Magdy et al. reported [80] on the spec­
trofluorimetric determination of ornidazole and miconazole nitrate
based on their quantitative quenching of Ag-NPs native fluorescence.
Ag-NPs were synthesized using Piper cubeba seed extract as a reducing
agent. FT-IR spectra of Ag-NPs were measured in the range of 4000–500
cm− 1, showing different functional groups including N–H (3448 cm− 1),
C–H (2924 cm− 1), C = O (1705 cm− 1), C = C (1622 cm− 1), C–N (1384
cm− 1), and C–O (1022 cm− 1) as demonstrated in Fig. 6.

3.3 . X-Ray diffraction (XRD)

XRD is an extensively applied technique for assessing the crystalline

size, lattice distortion, and shape by long-range order, but it is restricted
Fig. 2. Scheme of the set up for synthesis of Ag-NPs using laser ablation [43]. to non-uniform materials. At the atomic level, XRD is also performed for

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G. Magdy et al. Microchemical Journal 196 (2024) 109615

Fig. 3. Scheme for the Synthesis of Ag-NPs and application for determination of ONZ and MIZ [80].

Fig. 4. Schematic representation for the syntheses of Ag-NPs using a microwave, where the solvent is (a) pure glycerol and (b) glycerol/water mixtures. MW:
microwave [81].

the determination of the material structure. Typically, the XRD 3.4 . Dynamic light scattering (DLS)
approach has several limitations because of obtaining results only from a
single conformation/binding state of the sample, the difficulty in DLS can be utilized to explore the particle size distribution in solu­
growing crystals, and the low intensity [86,87]. Shameli et al. [88] used tion or suspension utilizing a monochromatic light source, e.g., a laser.
the XRD technique to clearly illustrate the crystalline nature of Ag-NPs, The DLS principle is based on observing the temporal fluctuation of
which were synthesized from Curcuma longa. Peaks at 2θ of 38.18◦ , light’s elastic scattering intensity [89].
44.25◦ , 64.72◦ , and 77.40◦ also indicated the 111, 200, 220, and 311 DLS is characterized by its non-invasive manner, short experiment
crystallographic planes of the face-centered cubic silver crystals, duration, accuracy in the determination of the hydrodynamic size of
respectively (Fig. 7). mono-disperse samples, low device costs, analysis of samples in a wide
range of concentrations, measuring diluted samples, as well as sensing of
higher molecular weight species but in small quantities. Nevertheless,

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G. Magdy et al. Microchemical Journal 196 (2024) 109615

dispersion of nanomaterials, crystallographic information, and compo­

sition at the nanometer scale [73]. On the other hand, there are specific
defects of TEM measurements, where a thin sample section and high
vacuum are essential to ensure ideal electron-beam penetration. Finally,
TEM is a very expensive technique (maintenance and acquisition costs)
and requires highly experienced and trained personnel [90,92]. Rastogi
et al. [93] reported a study that used Ag-NPs as a colorimetric sensor for
Hg2+ detection in an aqueous system. In this method, Ag-NPs were
produced from gum kondagogu (GK), which behaved as both stabilizing
and reducing agents. Through TEM analysis, the morphology of the
synthesized GK-AgNPs was easily identified to be spherical in shape and
5.0 ± 2.8 nm in size. Abd Elhaleem et al. [8] prepared Ag-NPs by
chemical reduction method using sodium borohydride as a reducing
agent, and further stabilization occurred by polyvinylpyrrolidone. TEM
Fig. 5. Ultraviolet–visible absorption spectrum of synthesized Ag-NPs using images of the prepared ANPs indicate spherical Ag-NPs with a size range
ginger extract [83]. of 14 ± 2 nm (Fig. 9) [8].

DLS functions are affected by numerous drawbacks, including difficulty

3.6 . Scanning Electron microscopy (SEM)
in correlating size fractions with a certain composition when particular
amounts of aggregates exist, interference in the scattering intensity from
One of the most popular techniques for investigating nanomaterials
dust particles, and relatively small particle size (1 nm − 3 μm) [90].
in electron microscopy (EM) is the SEM technique, which is based on
Mariam et al. [91] reported a spectrofluorimetric methodology for
obtaining images of high resolution after analysis of Ag-NPs through
studying the interaction between Ag-NPs and bovine serum albumin.
scanning with a focused, high-energy electron beam. The size, size dis­
DLS was utilized to illustrate the distribution of Ag-NPs’ particle size,
tribution, surface morphology, topography, shape, and aggregation of
where the mean particle size was found to be 62 nm, as presented in
nanomaterials can be easily acquired by SEM [94].
Fig. 8.
SEM has an advantage over TEM due to its ability to morphologically
characterize “thick” (>100 nm) samples. Lastly, when comparing both
3.5 . Transmission Electron microscopy (TEM) TEM and SEM images, it should be kept in mind that TEM provides in­
formation regarding the sample structure as a result of interaction with
In this approach, TEM pictures are used to display the morphological the entire sample volume, while SEM only gives information on the
and structural features of nanomaterials at atomic resolution. surface structure of the sample [95]. Ajayi et al. [96] used the SEM
Generally, TEM can provide the degrees of aggregation and approach to characterize the LG-AgNPs synthesized from the alkalinized

Fig. 6. FT-IR spectra of Ag-NPs [80].