Are Silver Nanoparticles in Anti-bacterials Harmful to Humans?

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Are silver nanoparticles in anti-bacterials harmful to humans?

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Silver nanoparticles are effective antibacterial agents with broad applications in medicine and healthcare. However, their potential cytotoxic effects on human cells cannot be overlooked. Further research is needed to develop safer formulations and mitigate the risks associated with AgNPs. By understanding the balance between their antibacterial efficacy and cytotoxicity, we can harness the benefits of silver nanoparticles while minimizing their harmful effects on human health.

Silver nanoparticles (AgNPs) have garnered significant attention for their potent antibacterial properties. They are widely used in medical and healthcare products to treat and prevent infections. However, the increasing use of AgNPs has raised concerns about their potential cytotoxic effects on human health. This article explores the antibacterial efficacy of silver nanoparticles and examines their potential harmful effects on humans.

Antibacterial Efficacy of Silver Nanoparticles

Silver nanoparticles exhibit a broad spectrum of antibacterial, antifungal, and antiviral properties. They can penetrate bacterial cell walls, disrupt cell membranes, and induce cell death by releasing silver ions. These mechanisms make AgNPs effective against both Gram-negative and Gram-positive bacteria, including multidrug-resistant strains  . Studies have shown that AgNPs can increase the permeability of bacterial cell membranes, produce reactive oxygen species, and interrupt DNA replication, leading to bacterial cell death .

Applications in Medicine and Healthcare

AgNPs are incorporated into various medical and healthcare products, such as wound dressings, antimicrobial textiles, and dental materials. They are used in prosthetic treatments, restorative treatments, endodontic treatments, orthodontic treatments, periodontal treatments, and dental implants. The combination of AgNPs with antibiotics has shown a synergistic effect, reducing the dosage needed and preventing secondary effects associated with both .

Potential Harmful Effects on Humans

Despite their antibacterial efficacy, silver nanoparticles pose potential risks to human health. In vitro studies have reported that AgNPs are toxic to several human cell lines, including bronchial epithelial cells, umbilical vein endothelial cells, red blood cells, and liver cells. The cytotoxicity of AgNPs is dose-, size-, and time-dependent, with smaller particles (≤10 nm) being particularly harmful. AgNPs can cross the blood-brain barrier and accumulate in organs such as the liver, spleen, kidney, and brain, raising concerns about their long-term effects.

Mitigating Cytotoxicity

To reduce the cytotoxicity of AgNPs while maintaining their antibacterial efficacy, researchers have developed novel nanocomposites. For instance, AgNPs decorated with carboxyl betaine groups exhibit pH-responsive surface charge switchable properties. These nanoparticles are compatible with mammalian cells at neutral pH but strongly adhere to bacterial surfaces at acidic pH, enhancing their antibacterial and antibiofilm efficiency. Additionally, polysaccharide-capped AgNPs have shown reduced cytotoxicity towards mammalian cells while effectively inhibiting bacterial growth and biofilm formation.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

David W Grainger has answered Uncertain

An expert from University of Utah in Nanotechnology, Biological Materials, Drug Use, Biomedical Engineering, Medical Biotechnology, Pharmaceutics

One can find any answer one wishes to find in the current literature published on this topic.  This might be expected since pharmacology and toxicology claims for any substance in the human body depend on so many variables, and very few studies are conducted on humans to date.  While amount (dose) is certainly central to such determinations, the ancient Paracelsus doctrine that “the dose determines the toxicity” is only part of the silver story.  The route of dosing (e.g., oral, nasal, inhaled, transdermal, subcutaneous, intravenous) is critical to determining any substance’s safety or adverse effects in the body.  Additionally, the substance’s bioavailability – how much of that substance gains access to the bloodstream from a given dose and certain route of administration – is also an essential attribute for determining pharmacology and toxicology. Bioavailability is complex, drug-specific, and different for each person, depending on their health status, disease, physiological factors, diet, genetics, and other variables.   How silver nanoparticles are transformed in the body into soluble silver ions determines much subsequent possibilities for a variety of possible effects that can range from no effect to toxicity. Despite enormous published literature on the topic, little validated scientific consensus exists in humans to date for silver exposures.

Therefore, given these variables, a general answer to this question of nano-silver safety in human use is highly uncertain from data currently published, the preponderance of mouse studies that may not reflect the human condition, and the highly variable, unknown and unvalidated quality of nano-silver compounds used both in published studies and available over the counter for unregulated human use).  

Emerging consensus seems to favor the idea that silver nanoparticles must dissolve to silver ions (through processes of metallic silver dissolution and oxidation to ionic silver) to enact significant antimicrobial activity.  Silver ion toxicity to human cells is well-reported, but evidence for distinct metallic silver nanoparticle toxicity to human cells and tissues is less convincing and likely highly dependent on test conditions.  Additionally, the quality, stability and chemistry of silver nanoparticles determines how easily oxidized they are and how readily they dissolve in human fluids and conditions.  No silver chemistry-specific product quality controls or mandated standards exist for any of the myriad silver-based consumer products mass-marketed with diverse unvalidated claims.  While total silver content might be reported for a silver product (e.g., ppm or mg/ml silver), the actual state of that silver, its chemical condition and its physical form are neither controlled or standardized.  This high variability of silver “condition” present in any formulation therefore is an intrinsic variable that confounds direct comparison of silver studies and silver products for possible human use.

A last safety consideration is the impact of oral silver on the human gut microbiome.  Antimicrobial properties known for silver ion are broad and general.  Oral ingestion of silver focuses this silver dosing directly on the gastrointestinal tract tissues before it might be absorbed for distribution via the bloodstream.  The high natural chloride ion content of the stomach (from ubiquitous strong stomach acid, HCl) produces some chemical confusion for how nano-silver administered orally might be transformed in the stomach to another compound, silver chloride, exhibiting limited solubility in water.  Both metallic silver nanoparticles and transformed silver chloride would then be passed from the stomach into the small intestine. There they would experience an enormous spectrum of different biochemical and physical stimuli as they transited the intestinal tract over the course of many hours, huge pH swings, and diverse tissue and mucosal exposures.  How metallic silver and silver chloride solids interact and dissolve in this environment depends on the subject’s intestinal physiology (rodent versus human differences), diet (fasted state? Western diet, vegan?) and possible local disease (i.e., abnormal stomach acid secretion, and intestinal oxidative conditions that influence silver’s chemistry and therefore bioavailability).  But it is precisely these local gastrointestinal conditions and subsequent conditioning of the oral silver dose that determine 1) how silver affects local intestinal health, and 2) how much oral silver dose might be absorbed systemically to enter the bloodstream.  Silver particle dissolution to silver ions, its absorption and biodistribution are not well understood in this environment.   Many possibilities are not verified, including the important effects of human diets and human physiological and microbiome differences on silver bioavailability.

Based on silver’s widely recognized antimicrobial properties, it would be anticipated that oral ingestion of silver ions (e.g., soluble silver compounds, silver salts, silver complexes, including some silver nanoparticles), would indiscriminately affect or kill microbial populations living symbiotically in the human gut.  These commensal microbial communities are essential for many aspects of human health and well-being.  Non-selective killing of these communities using many administered clinical antibiotics is now increasingly recognized as a general health risk.  Oral silver has also been scrutinized for such risks.  Orally administered silver is reported to produce diverse effects (spanning no effect to toxic effects) in rodent dosing models using several nano-silver compounds.  One limited nano-silver human oral dosing study showed no evidence for general overt human toxicity but did not look at human microbiome-specific markers (Nanomedicine: NBM 2014;10:1-9, http://dx.doi.org/10.1016/j.nano.2013.06.010).  

In summary, like so many drug exposure studies, published work on nanoparticulate silver human exposure to date has little consensus due to the highly variable nature of the study designs, unvalidated reagents, variable silver dosing and routes of administration, difficulty extrapolating dosing and effects from cell cultures to rodent to human subjects, food intake issues, and the varied responses observed.  More importantly, few studies are actually statistically powered to make confident human safety assessments.  Therefore, many silver nanoparticle answers are published that do not directly correlate to human conditions; many human conditions and doses are not compared or controlled; no real substantive health-based conclusions about nano-silver safety in humans is possible based on scientific evidence.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Jorge Padrão has answered Unlikely

An expert from University of Minho in Biotechnology

In my opinion, there is no linear black and white answer for this question. If we analyse the toxicity results of silver nanoparticles against mammalian cell lines, their cytotoxicity is undeniable. Nevertheless, some researchers decreased silver nanoparticles toxicity by applying some strategies, namely embedding them in a matrix.

Now, does this cytotoxicity imply a considerable and irreparable damage to the human body? If used sporadically or rarely, and as a topical or clinical application, my interpretation of the available data inclines me to answer no. However, a general and continuous application of silver nanoparticles may eventually lead to grievous health problems, due to the constant exposure to reactive oxygen species generated by the silver.

Finally, and more importantly, if an advanced antibacterial silver nanoparticle application is used to treat a severe infection of multidrug resistant bacteria, I must affirm that it will do more good than harm.

Therefore, considering that the silver nanoparticles would solely be used in clinical applications, my answer is unlikely.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Peng Zhang has answered Uncertain

An expert from University of Cincinnati in Nanotechnology, Materials Chemistry

It depends on the amount of silver nanoparticles.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Bo Peng has answered Likely

An expert from Oxford University in Materials Chemistry

Although Ag nanoparticles posse superior antibacterial activity, their cytotoxicity in human body has not fully investigated. Preliminary results show that they may permanently damage the function of normal cells in mammal, e.g. rat.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Qing-Hua Xu has answered Near Certain

An expert from National University of Singapore in Materials Chemistry

Silver metal itself is not toxic to human. Silver ions and silver nanoparticles can be used as anti-bacterial agents. They are toxic to bacteria. They can kill human cells due to the similar mechanism. Therefore they are also toxic to human cells to the similar extent.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Luigi Torre has answered Likely

An expert from University of Perugia in Materials Science

Rasouli, H. Devil’s hand conceals behind the obscure side of AgNPs: A letter to the editor (2019) International Journal of Biological Macromolecules, 125, pp. 510-513.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Krishan K Selwal has answered Near Certain

An expert from Deenbandhu Chhotu Ram University of Science and Technology in Biotechnology, Microbiology, Cell Biology

Well, silver Nanoparticles could be harmful for human beings. It will release silver ions in presence of fluids and silver ions have well documented adverse effects to certain types of cell. The effects includes cytotoxic, genetic damages and oxidative stress by silver ions.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Shuoqi Li has answered Uncertain

An expert from Shandong University of Science and Technology in Nanotechnology

Only the heavy metals in elemental forms would be harmful to humans. So for now, if the silver nanoparticles are coated with a more stable dispersant, a double layer will be formede and no elemental silver will be released during its contact with the human body. However, if the silver nanoparticles are only mechanically dispersed, it may cause irreversible damage to the secondary structure of the protein after use by the human body.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Abdelrahman M Abdelgawad has answered Near Certain

An expert from North Carolina State University in Materials Chemistry, Chemistry

Nanomaterials in general have very small sizes. strongly believe that the small size allows the particle to penetrate the outer cellular membrane of the living cells and accumulate there.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Ljubica Tasic has answered Unlikely

An expert from University of Campinas in Nanotechnology

Silver ions, silver(I) and silver(0) nanoparticles show excellent antimicrobial properties and have been used for centuries in day-a-day life. They might be toxic in high concentrations as all metallic ions, which are not micro elements, nevertheless, quantities used in anti-bacterials are low and unlikely to harm humans.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Selvankumar Thangaswamy has answered Uncertain

An expert from Mahendra Arts and Science College in Biotechnology

Any metal is in metal form is non toxic, if it is combined with any oxides and other metals or metal composites is toxic to cells.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

G Luna-Barcenas has answered Near Certain

An expert from Cinvestav Queretaro in Materials Chemistry

Silver was the most used bactericide agent during WWII with relatively good success; however, due to the “abuse” in its use it caused several health problems to humans. Silver nanoparticles exhibit different bactericidal effects than “just traditional silver” and its action against different bacteria has been proven effective; however, the correct assessment of its harm to humans is still a debate in the scientific community. Extremely low concentrations of silver nanoparticles (<0.001 wt%) exhibit good bactericide effect with minimal toxicity to humans.

 

Are silver nanoparticles in anti-bacterials harmful to humans?

Christopher Q Lan has answered Likely

An expert from University of Ottawa in Biotechnology, Nanotechnology

At least one study showed some toxicity (incompatibility) of bare AgNPs (Amit Kumar Bhunia et al 2015 J. Phys. D: Appl. Phys. 48 235305). Here is the abstract of the article: The interactions of human hemoglobin with protein capped silver nanoparticles and bare silver nanoparticles were studied to understand fundamental perspectives about the biocompatibility of protein capped silver nanoparticles compared with bare silver nanoparticles. Bare silver (Ag) nanoparticles (NPs) were prepared by the chemical reduction method. High resolution transmission electron microscopy (HRTEM) analysis along with absorption at ~390 nm indicated the formation of bare Ag NPs. Protein coated Ag NPs were prepared by a green synthesis method. Absorption at ~440 nm along with ~280 nm indicated the formation of protein coated Ag NPs. The biocompatibility of the above mentioned Ag NPs was studied by interaction with human hemoglobin (Hb) protein. In presence of bare Ag NPs, the Soret band of Hb was red shifted. This revealed the distortion of iron from the heme pockets of Hb. Also, the fluorescence peak of Hb was quenched and red shifted which indicated that Hb became unfolded in the presence of bare Ag NPs. No red shift of the absorption of Soret, along with no shift and quenching of the fluorescence peak of Hb were observed in the presence of protein coated Ag NPs. A hemolysis assay suggested that protein coated Ag NPs were more biocompatible than bare one.

The article did not discuss the nature or mechanism of the observed interactions between human hemoglobin with bare silver nanoparticles. One possible reason is that AgNG could be easily oxidized to Ag ions, which is much more reactive than Ag and may cause some detrimental effects such as metallic replacement of the ion in hemoglobin by silver ion. (This is my speculation. I have neither experimental nor literal data to support it).

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