Review on Silver Nanoparticles.

Komal Bhau Patil *, Momin Abrarul Haque, Bhaminee Madhukar Patil, Sanika Naresh Gaikwad, Tanmayi Bharat Shinde, Mohd. Salman.

M. S. College of Pharmacy, Gaurapur-Kudus Rd, Dist. Palghar, Maharashtra 421312.

Abstract: Nanoparticles are small, non-biodegradable polymers with a diameter of 1 nm to 1000 nm. They have a large surface area and high surface-to-mass ratio, making them suitable for binding, adsorption, and carrying drugs, probes, and proteins. Nanoparticle carrier systems allow for entrapment or encapsulation of the body over a specified treatment period. There are two main classes: soluble carrier systems, where the drug is conjugated to the carrier, and particular carrier systems, where the drug is surface-bound or entrapped within the carrier..   Keywords: Anticancer, Antibacterial activity, Bacterial resistance, Cancer therapy, Silver nanoparticles.

Corresponding Author: Komal Bhau Patil Email ID: komalpatil0611@gmail.com

Article History Received:        24/10/2023 Revised:          04/11/2023 Accepted:        05/10/2023 Published:       06/11/2023

 

 

 

 

 

 

 

 

 

 

INTRODUCTION

Nanoparticles are small colloidal particles made up of non-biodegradable and biodegradable polymers whose diameter is around 1 nm to 1000 nm. Nanoparticles possess larger surface area and their surface-to-mass ratio is extremely high compared to other particles. The nanoparticles can bind. Adsorb and carry other compounds such as drugs, probes, and proteins due to large surface area. The nanoparticle carrier system permits entrapment/encapsulation of the body over a specified treatment period.  To reach a desired target, drugs can be chemically modified using a pro-drugs approach or a use a carrier system. There are two types of carrier systems: soluble carrier systems and insoluble carrier systems. (The medication is conjugated to the carrier in these systems.) b. Specific carrier system (In this case, the medicine is either surface-bound or entrapped within the carrier, which can include liposomes, microspheres, and nanoparticles.) To encapsulate pharmaceuticals into the solid core, both metallic and polymeric Nanoparticles are utilized.[i]^,[ii]

 

 

 

HISTORY:

Silver has a long history of its usage in different forms and for different purposes. For centuries, the anti-bacterial properties of silver have been used to fumigate potable water with strong silver containers. Anecdotal information suggests that Nanosilver was used in ancient Egypt and Rome. The Macedonia’s used silver plates to improve wound healing and Hippocrates used silver in the treatment of ulcers. In 1520, Paracelsus utilized silver orally and silver nitrate as a caustic to cure wounds, a procedure that is still practiced today. In 1614, Angelo Sala administered silver nitrate internally as a counterirritant, as a purgative, and for the treatment of brain infection. C.F.S.  Crede is credited with the first scientific publication to describe the medical use of slivers in the late nineteenth century.  Crede used eye drops containing 1% silver nitrate solution to treat eye infections in newborns. Colloidal Nano silver is used in the United i.e. suspension of silver particles in a liquid, which was registered in 1954 as a biocidal material and has been used in medication for nearly one hundred years. The use of silver for antimicrobial properties is not a recent development.[iii]

 

PROPERTIES OF SILVER NANOPARTICLES:

They have definite physicochemical properties such as optical properties. Magnetic property, catalytic property, and antimicrobial property at the Nono stage which characteristics consequences in superior chemical reactivity, biological activities, and catalysis behavior compared to larger particles of identical chemical composition. [iv]

·         Morphologies and size:

The morphologies and size of AgNPs depend greatly on the concentration of the solution.176 For instance, their distribution and size vary with the concentration of both the polysaccharides and the precursor metal salts.

·         Toxicity property:

The unique chemical properties of AgNPs can be well exploited in several applications. Studies have proven that AgNPs are very effective as antimicrobials against bacteria, viruses, and eukaryotic microorganisms. Since silver nanoparticles AgNPs are known to exist in several commercial products such as contraception devices and feminine hygiene products, they may have adverse effects on the human reproduction system.

·         Optical properties:

Several studies have shown that AgNPs absorb electromagnetic radiation in the visible region from 380 to 450 nm using a phenomenon known as the excitation of Localized Surface Plasmon Resonance LSPR. The spherical shape of AgNP synthesis by glucose reduction was found to have surface Plasmon Resonance at 400 nm. In the same shape of AgNPs obtained from NaOH reduction, their study found that the Nanoparticles absorbed the maximum electromagnetic radiation at 420 nm.

·         Thermal properties:

Thermal behavior is an important aspect that is considered in detail in the production or application of a material. A remarkable property of metal nanoparticles is their low melting temperature due to the Thermodynamic size effect. It was widely applicable for several purposes.

·         Electrical property:

AgNPs with their unique electrical properties can be utilized in electronic devices. The electrical conductance of AgNPs varying in size from 4 to 12 nm that were grown in glass-ceramic was examined.211 The DC electrical resistance of AgNP films was measured in the temperature range 80- 300 K. It was found that the surface resistivity increases linearly with temperature rising from 120 to 300K.

·         Catalytic property:

AgNPs have been utilized as an effective catalytic agent for the reduction of various dyes such as methylene blue, yellow 12, 4 nitrophenol, Rose Bengal, eosin, and methyl orange. 215- 219 AgNPs synthesized using the peach kernel shell method were found to have the capability as a catalyst for the reduction of 4- nitrophenol to 4- aminophenol.215 The reduction process could take 200 min without the catalyst.[v]

·         Biological properties:

Currently, the unique antimicrobial properties of AgNPs have led to their application in areas such as clothing manufacturers, food preservation, and water purification more importantly, AgNPs are being increasingly utilized in the medical industry due to their antibacterial, antifungal, antiviral, anti-inflammatory, and osteo inductive effects as well as their ability to enhance wound healing.

·         Antibacterial properties:

The antibacterial effects of silver nanoparticles have been used to control bacteria growth in a variety of applications, including dental work, surgery applications, wounds, and burns treatment devices. It is well known that silver ions and silver-based compounds are highly toxic to microorganisms. The introduction of silver nanoparticles into bacteria cells can induce a high degree of structural and morphological changes, which can lead to cell death. Scientists have demonstrated that the antibacterial effects of silver nanoparticles are mostly due to the sustained release of free silver from the Nanoparticles, which serve as a vehicle for silver ions.

·         Antiviral properties:

Various viruses, such as influenza, hepatitis, hepatitis, simplex virus (HSV), and human immunodeficiency virus (HIV), can be life-threatening. Although many vaccines have been developed against viruses, medicine has yet to develop a broad–spectrum antiviral vaccine. Furthermore, these viruses are developing antiviral resistance to current treatment and classical antiviral drugs, especially in immune-compromised patients. In light of this, there is a pressing need for the development of new antiviral agents against a broad spectrum of viruses. AgNPs act as a broad-spectrum agent against a variety of viral strains and are not prone to developing resistance.

·         Antifungal property:

Long–term, repetitive administration of standard antifungal drugs leads to increased fungal resistance, especially by the Candida species. Therefore, New antifungal agents are constantly being investigated. AgNPs have displayed many antifungal properties against common fungi and thus offer potential as an effective antifungal. [vi]^{,[vii],[viii],[ix]}

 

CHARACTERISTICS OF SILVER NANOPARTICLES:

Characteristics of nanoparticles are important to understand and control nanoparticle synthesis and application. Characteristics are performed using a variety of different techniques such as transmission and scanning electron microscopy (TEM. SEM), atomic force microscopy (AFM) dynamic light scattering (DLS) X rays’ photoelectric spectroscopy (XPS), powder X rays diffractometry (XRD), Fourier transforms infrared spectroscopy (FTIR), and UV Vis spectroscopy.  These techniques are used for the determination of different parameters such as particle size, shape, crystallinity, fractal dimension, pore size, and surface area. Moreover, orientation, intercalation, and dispersion of Nanoparticles and nanotubes in nanocomposite material could be determined by these techniques.[x]

 

APPROACHES SILVER NANOPARTICLES:

Biological Approaches 

The Biosynthesis of Ag NPs and their stability is a significant part of industrial production. Consequently, it's crucial to properly monitor the circumstances surrounding reactions.[xi]

·         From bacteria:

The possibility of utilizing microorganisms in the production of AgNPs has just come to light. For instance, Ag NPs were produced inside the cell using pseudomonas stutzeriAG259- isolated from a silver mine. A. Calcoaceticus, B. Amyloliquefaciens, B. Flexus, B. Megaterium, and S. Aureus are a few other gram-positive and gram-negative bacteria strains that have been employed for the extracellular and intracellular production of Ag NPs. These Ag NPs have the following shapes: disk, cuboidal, hexagonal, and triangular. They were created utilizing cells, aqueous cell-free extract, or culture supernatant.[xii]

·         From fungi: 

The Biosynthesis of Ag NPs from both pathogenic and nonpathogenic fungi has been investigated extensively. It has been reported that silver ions are reduced extracellularly in the presence of fungi to generate Ag NPs in water.[xiii]

 

·         From plants:

Plant-related plants such as leaves, stems, roots, shoot, flowers, barks, seeds, and their metabolites have been successfully used for the efficient biosynthesis of nanoparticle.[xiv]

Physical Approaches:

The physical synthesis of AgNPs includes the evaporation–condensation approach and the laser ablation technique. Both methods may produce huge amounts of highly pure AgNPs without the use of chemicals that release hazardous substances and endanger human health and the environment. However, agglomeration is frequently difficult since capping agents are not applied. Furthermore, both processes consume more electricity, have a longer synthesis time, and require more complex equipment, all of which raises their operational costs.[xv]

Chemical Approaches:

·         Chemical reduction:

Chemical reduction is the most common approach for the Synthesis of AgNPs using organic and inorganic reduction agents. This is done by continuing through a single process to generate a colored silver solution, this is due to the surface of a metal being free of charge in the conduction band and positively charged nuclei. Then, the formation of a long–lived cluster of silver is formed and confirms the Synthesis of AgNPs. In general, the one-pot method of reduction of AgNO₃ using a different reducing agent such as sodium citrate, ascorbate, sodium borohydride (NaBH4), elements hydrogen, polyol process, N, N dimethylformamide (DMF), Ascorbic acid, poly (ethylene glycol)- block copolymers, hydrazine, and ammonium format is applied for reduction of silver ions (Ag) in the aqueous or no aqueous solution.[xvi]

·         Microemulsion techniques:

·         Microemulsion techniques have various applications in the chemical and biological field due to their exceptional properties such as ultralow interfacial tension, huge interfacial area, Thermodynamic constancy, and the capability to solubility immiscible liquid. The microemulsion method assures to be one of the flexible preparation techniques that allows to Organize the particle properties such as the mechanism of particle size control, geometry, morphology, homogeneity, and surface area.[xvii]

·         Microwave-assisted synthesis:

·         In contrast to the traditional heating method, microwave synthesis uses variable rate microwave radiation to reduce silver nanoparticles. The technique gives up a more rapid reaction and gives a higher concentration of silver nanoparticles with the same temperature and exposure.[xviii]^,[xix]

·         Photochemical Approach:

In the photochemical techniques mainly two different methodologies are implemented for the Synthesis of AgNPs: (a) Photophysical and (b) photochemical techniques. In the photochemical techniques Ag- NPs are synthesized by Photoreduction of precursor or Ag ions using photochemical activated intermediates such as radical. In one of the methods Ag- NPs were synthesized using UV radiation and an aqueous solution containing Triton ×100 which acted as stabilizing agents.[xx]

 

FACTORY AFFECTING ON SILVER NANOPARTICLES:

·         Factory affecting particles Size:

The factory affecting the size of AgNPs was also investigated. Various studies were performed where the dispersants, reducing agents, and amine as well as their amounts were varied. Furthermore, the influence of temperature on the size was also investigated.

·         The size of AgNPs:

The size of AgNPs was obtained by TEM, and the diameter distribution of AgNPs was measured with zeta size Nono series (Malvern Instrument). The distribution ranges of AgNPs – A are approximately from 7 nm to 40 nm. Although a few larger particles (about 0.8%) exist, the diameter of the majority of particles (99.2%) is less than 10 nm. This indicates that the synthesized AgNPs -A have a narrow distribution of diameters and an average diameter of approximately 10 nm.

·         The Influence of Dispersants:

                    Polyvinyl pyrrolidone (PVP) plays an important role as a surfactant in the formation of AgNPs. PVP used as a dispersant can protect Nanoparticles in AgNP preparation because it covers the surface of Nanoparticles to form stable colloids, which is useful for industrial manufacturing. The amount of (PVP) as a dispersant influences the size of AgNPs. When only a small amount of PVP is used, agglomeration takes place as a result of incomplete covering of AgNPs with PVP. An appropriate weight ratio of PVP/AgNO3 should be optimum to produce small-sized AgNPs. In this case, the entire surface of AgNPs is coated with PVP.  Consequently, the agglomeration is prevented by PVP keeping the silver particles separate. However, the size of the metal nanoparticles increases when excess PVP is added. This indicates that excess PVP does not further reduce the size of the colloid.

·         The Influence of Amines:

The amine plays an important role in the reduction of silver ions in aqueous solution. Na3Ct can be used not only as a dispersing agent but also as a reducing agent. However, it is a weak reluctance, and its reducing ability is dependent on the PH of the solution. When Na3Ct alone is used as a reducing agent, a higher temperature is usually required to promote reduction (100°C). In our study, however, the reactions occur rapidly at room temperature with the addition of DMAE. The reaction mechanism of AgNPs fabricated using a dispersing agent (DA) can be supposed as follows:

DMAE+ H20 =DMAE+OH-(1)

Ag++DA=Ag (DA)+(2)

Na3Ct(C-OH) +20H -=Na3Ct(C=O) +H2O+2e-(3)

Ag (DA)++e-=Ag (DA)+DMAE (4)

When the amine is dissolved in water, it withdraws a hydrogen ion and leaves a hydroxyl ion in solution. The hydroxyl ions oxidize the OH group in Na3Cl and an electron is released in the process. It is thought that the amine acts as a catalyst that can accelerate the reaction. Moreover, in this case of AgNPs -C using benzoic acid as a dispersing agent, it is clear that benzoic acid plays a role in not only reducing agent but Also stabilizing agent in this process. Other amines were also examined. It is found that smaller AgNPs-C can be obtained under relatively weak alkaline conditions.

·         The Effect of temperature

As described in our previous work, when the reaction was performed at 50°C, the reaction mixture quickly turned brown, and a black powder was collected as the final product. TEM image of AgNPs showed that large silver particles have formed and the particles are not spherical, appearing to be linked. This probably results from the coordinator among silver particles surface covered with PVP at high temperatures.  On the other hand, when the reaction was performed at 10°C, the rate of reaction was slow and the color of the solution began to change only after 3 h. [xxi]^,[xxii]

            

BIOMEDICAL APPLICATIONS OF SILVER NANOPARTICLES:

·         Antibacterial characteristics of silver nanoparticles:

Silver nanoparticles have piqued the interest of biomedical researchers due to their appealing and unique Nano-related properties, such as their high intrinsic antimicrobial efficiency and non-nature. Some critical aspects of AgNPs' specific antimicrobial properties imply their intrinsic physical and chemical properties, which include maintaining AgNPs' nanoscale size, improving their dispersion and stability, and avoiding aggregation. Many studies have been conducted to demonstrate that the anti-pathogenic activity of AgNPs is superior to that of silver ions.[xxiii]

The primary advantage of Nanosilver-based biomaterials designed for inconvenient antibacterial applications is that they exhibit intrinsic anti-pathogenic effects against both planktonic and biofilm-organized microorganisms. Silver cations, which can specifically bind to the thiol group of bacterial proteins, disrupt their physiological activity, and cause cell death, are responsible for AgNPs' bactericidal activity.[xxiv]^,[xxv]

·         Silver nanoparticles for Drug Delivery system:

In medicine, the pharmacokinetics and pharmacodynamics of drugs are as important as their intrinsic therapeutic effects. Since the specific and selective delivery and action of therapeutic agents have become one of the most researched topics for improving current human healthcare practice, nanoparticles have received a great deal of attention in the design and development of novel and improved drug delivery systems. In particular, AgNPs-based Nano systems were evaluated as suitable carriers of various therapeutic molecular, including anti-inflammatory, antioxidant, antimicrobial, and anti-cancer bio substances[xxvi]^,[xxvii]

·         Silver nanoparticles for Catheter Modification:

Central venous catheters (CVC) were first described by John E. Niederhuber in 1982; since then, these devices have become important therapeutic tools for diverse clinical conditions requiring malnutrition and replacement therapy (ex: renal disease and cancer.) CVCs are normally used to provide access to intravenous fluid administration, hemodynamic monitoring, drug delivery pathway, and nutritional support in critical I’ll patients. support in critical I’ll patients. Still, these medical devices are also a considerable source of a hospital–acquired infection and are considered a specific high-risk category of devices susceptible to microbially contamination and colonization phenomena.[xxviii]

·         Silver nanoparticles for Dental Applications:

Dental caries represents one of the most extensive oral cavity-related affections worldwide, being Also an economic burden. By enhancing the remuneration process and controlling biofilm development, nanotechnology-derived dental-related strategies aim to limit or even eliminate the clinical impact of caries. To prevent the pathogenic contamination of implants, proper tooth brushing techniques, prophylactic antibiotics, and antimicrobial mouthwashes are specifically recommended. Biofilms developed on dental implant surfaces may additionally cause inflammation lesions on the pair implant mucosa, thus increasing the risk of implant failure.[xxix]

·         Silver nanoparticles for Bone Healing:

Every year, millions of people worldwide are affected by distinctive and complex bone-related pathologies, including infectious diseases, degenerative and genetic conditions, cancer, and fractures. Unfortunately, the opportunistic contamination and colonization of orthopedic implants represent major concerns in osseous tissue replacement strategy, since they undergo regenerative and restorative processes through the intrinsic and complex bone remodeling mechanism. In terms of bone replacement procedures, AgNPs are normally used as doping material for synthetic and bio-inspired bone scaffolds, with relevant results being recently reported. [xxx]

·         Silver nanoparticles for Wound Healing:

Wound infection represents an important clinical challenge, with a major impact on patient morbidity and notable economic implications. Preventing wound dehiscence and surgical site infection is a challenging and essential aspect of current clinical practice. The skin is the most extensive and one of the most complex organs in the human body. But it can be easily affected by different harmful external factors. Physically or chemically induced cutaneous wounds may significantly disturb skin structural and functional integrity at different stages, leading to permanent disability or even death, depending on the severity of the injury. The wound healing process, as with any complex pathophysiological mechanism, includes different stages, such as coagulation, inflammation, cellular proliferation, and Matrix and tissue remodeling[xxxi]^,[xxxii]

 

TOXICITY:

AgNPs are amongst the most extensively used metal NPs and has played a crucial role in different field of biomedical and pharmaceutical application. The smaller size of the AgNPs makes it simple for them to pass through biological membranes and enter cells, where they can cause toxicity at different levels depending on the hyperactive microorganisms. AgNPs' toxicity is discovered to be related to characteristics like size, shape, quantity, accumulation, surface charge, and the synthesis techniques used.

Furthermore, the toxicity of AgNPs is dependent on the type of targeted microbe, which is related to the resistance mechanism of the microbe used to eliminate the unwanted complexes. Furthermore, the culture media to which the bacterial species are exposed has a significant impact on the bacterial response in toxicity assessments. Primarily, both the AgNPs and Ag+ ions released from the AgNPs are presumed to employ toxicity by stimulating membrane impairment, ROS generation, oxidation and denaturation of protein, dysfunction of mitochondria, damage of DNA, and obstruction of cell propagation.

AgNPs Produced from the green method are usually more toxic than those attained from the non-green methods. However, the development and application of AgNPs have ensued in public cognizance related to their toxicity and environmental impact. Interestingly, a contrasting fact has been observed related to the dose of AgNPs indorsing toxicity. In some studies, the AgNPs of particle size >50 nm reduced the sustainability in the tested human mesenchymal cells at a lower dose of 101 g/mL, however in a study no toxicity was reported even at a higher dose of 100 g/ml. Also, the stability of the samples has shown a significant role in an upsurge in toxicity by the stored AgNPs (water for 6 months) which is correlated with the release of Ag ions[xxxiii]^,[xxxiv]

 

CONCLUSION:

AgNPs are emerging as a next-generation application in numerous nanomedicines, and the potential benefits of AgNP as prominent nanomaterials in biomedical and industrial sectors have been widely acknowledged. The comprehensive research regarding silver nanomaterial has been explored in this review to understand the synthesis method and mechanism, characterization of physicochemical properties, and pharmacology. Among the various synthesis methods, biological green synthesis draws our attention as a promising alternative, due to its safety using natural agents and nontoxic chemicals. Diverse applications of AgNPs as plasmonic nanoantenna and biomedical and optoelectronic probes were also highlighted, Lastly, a better understanding of the cytotoxic mechanism of AgNPs merits future research to broaden their nanomedical application in diagnostics, therapeutics, and pharmaceutics.

 

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