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International Journal of Pharmacognosy and Chinese Medicine
ISSN: 2576-4772
The Scope of Nano-Silver in Medicine: A Systematic Review Int J Pharmacogn Chinese Med
The Scope of Nano-Silver in Medicine: A Systematic Review
Deep Inder1* and Pawan Kumar2
1Department of Pharmacology, Jamia Millia Islamia University, India
2Additional Director, DGHS, Karkardooma, India
*Corresponding author: Deep Inder, Associate Professor, Department of Pharmacology,
Jamia Millia Islamia University, India, Email: drdeep73@gmail.com
Abstract
Nano-silver has already been clinically explored in ancient medicine i.e ayurveda in the form of Raupya bhasma/rajat
bhasma. The resurgence of nano-silver has revolutionized not only as upcoming drug against anti-microbial drug
resistant nosocomial infections , but has also evolved in diagnostics, targeted drug delivery, nano-implants, nano-fillers in
dentistry, nano-cement in bones and as antiseptic and dis-infectants. Several clinical trials have demonstrated their
promise in bio-medical field for above mentioned areas. The only limitation observed in studies is its cumulative
potential resulting in toxicity of silver known as argyria i.e grey black discolouration of skin. Moreover few studies have
proved the presence of small quantities of heavy metals e.g mercury, arsenic, lead etc in ayurvedic formulations.
Therefore, more toxicity studies are required to establish the safety and efficacy of nano-silver. Once toxic profile of nano-
silver is established, it would be easy to apply uses of nano-silver firmly in various clinical aspects in medicine.
Keywords: Nano-silver; Antimicrobial resistance; Toxicity of silver
Introduction
Nano-silver has long been recognized as a medicinal
metal in ancient system of medicine i.e., ayurveda in India.
In golden period of ayurveda the fine metals, minerals and
their ores e.g. gold, silver, antimony, sand, gems etc were in
use for medicinal purpose [1]. No exact pharmacological
studies are evident so far claiming their authenticity. Very
limited numbers of reverse pharmacological studies have
been conducted so far to ascertain their safety and efficacy.
Traditionally, nano-silver is also known as ash of
silver/Raupya bhasma/Rajat bhasma [2]. Silver has long
been recognized as antibacterial drug from the time of
Hippocrates. The primary ore of silver is apparently the
sulphide and argentite, obtained from argentiferous galena
found in the zone of secondary enrichment of earth. Silver
is available as fluorides, chlorides, bromides, iodides,
hydrides, oxides, sulphides, nitrites and nitrates. Once the
metal has been obtained from its naturally occurring ore
by reduction process, it may contain foreign elements that
may alter or reduce the pharmacological properties of
metal [3].
In ayurveda, Rasa-shastra is the branch of medicine
dealing with processing and therapeutics of metals and
minerals drugs [4]. It lays down the various processes
used for the conversion of metal and minerals into organo-
metallic biocompatible form which can be easily absorbed,
distributed, metabolized and excreted by human body [5].
Organo-metallic preparations are processed using
physical, chemical and biological methods to make them
biocompatible [6]. The ashes of metals thus obtained are
actually the nano sized particles known as Bhasmas in
Review Article
Volume 2 Issue 2
Received Date: March 12, 2018
Published Date: April 03, 2018
International Journal of Pharmacognosy and Chinese Medicine
Deep Inder and Pawan Kumar. The Scope of Nano-Silver in Medicine: A
Systematic Review. Int J Pharmacogn Chinese Med 2018, 2(2): 000134.
Copyright© Deep Inder and Pawan Kumar.
2
ayurveda. Bhasmas have been reported to contain high
concentration of heavy metals [7]. But ayurvedic experts
claim bhasmas to be safe for human use. According to
Rasashastra these nano sized bhasmas/ashes undergo
various processes e.g. purification of metal/mineral
followed by levigation using some herbal extracts and
repeated calcinations till the loss of impurities in final
formulation [8]. Since ayurveda caters to about 80% of the
population in developing countries as per the estimate of
World Health Organization (WHO) [2]. Therefore, now
ayurvedic formulations are being evaluated for their safety
and efficacy by reverse pharmacological approaches to
prove their safety. Europe has banned almost all ayurvedic
products due to lack of adequate studies on safety data of
such products [9].
Nanosilver (NS)/ash of silver, is constituted by
aggregates of silver atoms ranging in diameter from 1 to
100 nm. Nanosilver Is the broad term used for
nanospheres or colloidal NPs, nanocrystals [10,11]. The
fruit extract of Emblica officinalis and leaf extract of
Achlypha indica, azadirachta indica, coriandrum sativum
etc are used as reducing agents to synthesize nano-silver
in laboratory. Latter bear excellent antimicrobial activity
against E. coli and V. cholera [12-14].
Scope of Nano-Silver
Nano silver is gaining popularity owing to its
antibacterial, antifungal, anti-inflammatory and analgesic
properties [15]. Scope of nano-silver is expanding day by
day and is emerging as a new area of research in medicine.
The use of nano-silver is highly commercialized in garment
industry where it is incorporated into fabrics for
neutralization of odor-forming bacteria [16]. Apart from
that, NS has been incorporated into food storage
containers for preventing food spoilage over long term
storage as preservative by inhibiting microorganism
growth [17]. The potential of nano-silver in infection
prophylaxis and treatment is now under consideration due
to emergence of antimicrobial drug resistance [18-20].
Silver has been used for gonococcal infections in
newborns since historical era. Silver sulfadiazine is the
golden remedy in the topical treatment of burn patients
[21,22]. Due to indiscriminate use of anti-microbial agents,
leading to resistant hospital acquired infections, there has
been seen a resurgence of interest in the area of nano-
silver [23].
The clinical use of nano-silver is limited due to its
toxicity profile as shown in many in-vitro studies. There is
a need to standardize the nano-silver formulations to
reduce toxic potential [24]. There is increasing interest in
nano-silver based diagnostic and therapeutic implications
in medical science. With nanotechnology, the particle size
of silver has been reduced to the nano scale with large
surface area-to-volume ratios leading to greater and easy
penetration of silver across membranes of microbes. This
further increases the efficacy against many bacteria and
few fungi. Anti-viral activity of nano-silver is still
questionable and research in this area is still in infancy
[24-26] (Table 1).
Sr. no
Modern nano-silver preparations
Traditional silver preparations (Raupya/rajat
bhasmas)
1.
Modern nano-silver particles are prepared by green
synthesis approaches using physical, chemical &
biological methods through nanotechnology [14].
Bhasma means an ash obtained through incineration,
repeated calcinations followed by purification which
involves incorporation of some other minerals and/or
herbal extracts. Bhasmas are actually synthesized using
physical and chemical methods [8].
2.
Particle size of silver produced ranges from 1-20nm
[12]
Bhasmas are generally with particle size of 10-15nm
and are prescribed with honey, ghee or some other
herbal medicines [2,6,8].
3.
Green synthesis approaches include polyethylene
glycol, glucose, starch as reducing agents. Biological
methods using some fungi, lactobacilli and lichens
which reduce silver to nanosilver. These methods
are eco-friendly and do not pose toxicity to living
systems and environment [14].
There is a lack of standardization of bhasmas may
lead to various toxicities in living systems [7,9].
Silver bhasmas can accumulate in skin and deeper
organs leading to toxicity known as argyria [2].
International Journal of Pharmacognosy and Chinese Medicine
Deep Inder and Pawan Kumar. The Scope of Nano-Silver in Medicine: A
Systematic Review. Int J Pharmacogn Chinese Med 2018, 2(2): 000134.
Copyright© Deep Inder and Pawan Kumar.
3
Nano-silver salt
(Modern)
Raupya bhasma
(Traditional)
Table 1: Comparative aspects of modern nano-silver and traditional silver preparations (Raupya/rajat bhasmas).
The present review is focused on emerging use of nano-
silver in the field of medicine especially in diagnosis and
therapeutics. We would also try to incorporate toxic
aspects of nano-silver.
Applied Aspect of Nano-Silver in Diagnostics
and Therapeutics
Nano-silver is the upcoming drug which has a very
significant role in diagnosis and treatment of disease.
Role in diagnostics and targeted drug delivery: Studies
on new targeted nano-silver as contrast agents for imaging
have proved their role in early detection of atherosclerotic
plaque at molecular level. Thus in future it will be possible
to facilitate customized medicine by collaborating imaging
and targeted nano-silver delivery approach [27,28].
Nanosilver also has plasmonic properties (light scattering,
absorbance and coupling), which make it suitable as
Biosensors. Nanosilver biosensors can effectively biosense
a large number of proteins that normal biosensors hardly
detect. This unique propery of nanosilver can be used for
detecting various abnormalities and diseases in the human
body at molecular level, including cancers [29,30].
The advantage of nanosilver in imaging is that do not
undergo photobleaching in contrast to fluorescent dyes.
Nano-silver biosensors can effectively be used to monitor
cellular events over an extended period of time [29].
Targeted drug delivery using nano-silver is an
important area of research these days .The aims of using
nano-silver in drug delivery includes:
a) Specific cell targeting and drug delivery
b) To reduce the toxicity of other concomitant drugs e.g
cancer chemotherapy
c) To maintaining therapeutic effects
d) to enhance the safety and efficacy of drug
e) Provide platform for fast development of new safe
medicine [31].
The plasmonic nature of nanosilver can also be used to
destroy cancer cells. The cells can be conjugated to nano-
silver coated anti-cancer drugs, which then absorb light
and convert it to thermal energy. The resultant thermal
energy can lead destruction of targeted cancer cells [32-
34].
Role in prophylaxis and treatment of infections: Nano-
silver particles can easily cross cell membranes and
biological fluids within the human body [2]. Nano-silver in
the form of ash of silver has been in use as an antimicrobial
agent since time immemorial in the form of metallic silver,
silver nitrate, silver sulfadiazine for the treatment of
burns, wounds and several bacterial infections. All forms
of silver exhibit broad spectrum antibacterial activity
against both gram positive and gram negative bacteria. In
ancient Greece silver was used to purify drinking water
[35-37].
Moyer had introduced the use of silver nitrate (0.5%)
for the treatment of burns. According to him, silver possess
antibacterial activity against Pseudomonas areuginosa,
and Escherichia coli and Staphylococcus aureus [21,22].
Nano-silver has a potential to act as fungicide against
Aspergillus, Candida and Saccharomyces [38]. Ales
Panacek, et al. [25] has demonstrated effect of nano-silver
pathogenic strain of Candida species by determining the
minimum inhibitory concentration and minimum
fungicidal concentration. They concluded antifungal
activity against Candida spp. at the concentration of 1mg/l
of Ag [25].
Hippocrates, advocated the dusting of silver powder on
infected wounds and ulcers to expedite healing. Silver has
been used since World War I in wound dressings for faster
healing and alleviation of inflammation and pain [39,40].
Humberto H Lara, et al. [41] have given some evidences
regarding anti-viral activity of nano-silver [41]. Sun and
colleagues showed that nano-silver has cytoprotective
effect towards HIV-1-infected helper cells. Nanosilver may
interfere with the fusion of the viral membrane, thus
inhibits viral penetration into the host cell.
International Journal of Pharmacognosy and Chinese Medicine
Deep Inder and Pawan Kumar. The Scope of Nano-Silver in Medicine: A
Systematic Review. Int J Pharmacogn Chinese Med 2018, 2(2): 000134.
Copyright© Deep Inder and Pawan Kumar.
4
Nano-Silver Impregnated Surgical Dressing/
Meshes and Equipments
In the modern era of nanotechnology, there is a trend of
using of Nano-silver impregnated dressings with the base
of foam, hydrocolloid gel, gauze or film. U.S. Food and Drug
Administration (FDA) have cleared many of such nano-
silver impregnated dressings [42]. The nano-silver ladden
dressing change colour when the antibiotic is released.
This dressing has great potential in treating burn patients
who are susceptible to toxic shock syndrome. With the
advent of such system, there can be a reduction in
antibiotic resistance. Silver nanoparticles impregnated
ointment healed the wound in 3 days in contrast to any
normal ointment (control), that took 7 days to heal [39,42].
Nano-silver is used in bone cements that are used as
artificial joint replacements. Nano-silver coated
polypropylene mesh is said to have good antimicrobial
activity and can be an ideal candidate for surgical meshes
[43,44]. Due to broad spectrum of antimicrobial activity of
nano-silver nanoparticles, it is used in disinfectants and
hand washes [45]. Nano-silver coated intravenous
catheters, endotracheal tubes, bone cements,
contraceptive devices, wound dressings and dental fillings
are being used these days to prevent microbial infections
[46-51].
Mode of anti-microbial action of Nano-silver
The proposed mechanisms of antimicrobial property till
date are:
a) Uptake of free nano-silver in microbial (bacteria, fungi)
machinery followed by disruption of ATP production,
DNA replication and inhibiting bacterial/fungal
functional proteins [52].
b) Generation of Reactive oxygen species (ROS) and free
radicles, which cause direct damage to cell membranes
[53].
There are certain reports regarding mode of action of
nano-silver against viral infections, where nano-silver
inhibits fusion of virus with host cell. The positive charge
on the Ag+ ion is critical for its antimicrobial activity. Ag+
being positively charged has high affinity to bind to
negatively charged microbial cell membrane. Limitation of
nano-silver is that excess of nano-silver gets deposited in
host cells leading to its toxicity, known as argyria [54,55].
Sondi, et al. [52] reported that concentration of nano-silver
is the deciding factor for its anti-microbial potential. Once
nano-silver in adequate concentration enters microbial cell
wall , it results in formation of pits in the cell wall of
bacteria; consequently disturbing the membrane
permeability, progressive release of lipopolysaccharide
molecules and membrane proteins resulting in cell death
[52-55].
Figure 1: Diagram showing the effect of nano-silver on
bacterial cell.
Role of Nano-Silver in Dentistry
In dentistry, dental nano-silver robots are gaining
attention, which may be utilized for treating
hypersensitive teeth, in the identification and destruction
of pathogenic bacteria residing in plaque. The technology
can also be helpful to design nanocomposites with
nanofillers for enhanced durability of aesthetics and
impressions material with nanofillers for precise tissue
detail [56-58].
Discussion and Conclusion
The medical properties of silver have been known for
over 2,000 years. The unique properties of nano-silver are
attributed to the physical and chemical processes it
undergoes during its synthesis. Nano-silver thus obtained
imparts excellent antimicrobial properties. Several studies
on nano-silver have demonstrated anti-bacterial,
antifungal, antiviral, anti-inflammatory and analgesic
properties. Owing to these beneficial effects, nano-silver
has emerged as a new drug in the field of medicine for
various medical applications e.g. Anti-microbial drug,
targeted drug delivery in cancer chemotherapy,
intravenous nano-silver coated catheters, in dentistry and
many more. Still extensive research is required to fully
understand their exact mechanism of action, synthesis,
characterization, and possible risk of toxicity. As we know
that in vitro conditions are very much different from in
vivo conditions, the results obtained in in vitro studies
cannot be completely applicable to living systems.
Therefore, long-term toxicity studies of nano-silver must
be conducted to establish the quantum of risk associated
with toxicity. This would facilitate prescribers regarding
the dose limit to be used in human for an indication. Thus
International Journal of Pharmacognosy and Chinese Medicine
Deep Inder and Pawan Kumar. The Scope of Nano-Silver in Medicine: A
Systematic Review. Int J Pharmacogn Chinese Med 2018, 2(2): 000134.
Copyright© Deep Inder and Pawan Kumar.
5
it can be concluded that nano-silver may be the excellent
choice especially against anti-microbial drug resistance
and hospital acquired infections, if used with precaution
keeping in mind the toxic aspects.
Conflict of interest: The authors declare that there is
no conflict of interest regarding this study.
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