Therapeutical Uses of Silver Nanoparticles

Aspects of a review by Carolina Santos and Marcelo Seckler of the Department of Chemical Engineering, University of Sao Paulo, Brazil. This review discusses Silver Nanoparticles (AgNPs) in biomedicine.

Antiviral Activity

The antimicrobial efficacy of AgNPs have been widely analyzed and demonstrated during the last decade, but demonstration of their activity against viruses as a potential weapon is recent. As a result of common antivirals being prone to the development of drug resistance, AgNPs are emerging as one of the easiest options for the control of viral diseases because of their remarkable antiviral activity and the possibility of offering a unique broad spectrum treatment option. In fact, AgNPs are active on a broad range of viruses, regardless of each single specific virus characteristic, and present a lower possibility of developing resistance compared with conventional antivirals. Nanoparticles have strong antiviral potential and because of their multiple interactions with glycoprotein receptor and/or viral envelope. They can inhibit the viral multiplication inside the host cell by preventing the replication or blocking the entry of virus particles inside the host cell. Depending on the interaction and virucidal effect, they have huge potential not only to face the challenge posed by viral infections but also enhance the quality of existing antiviral therapies.

Many successful attempts have been made to study the antiviral role of AgNPs without capping agent on the growth inhibition of viruses, such as, influenza virus, Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2). Also coxsackievirus tacaribe virus (TCRV), Vaccinia virus (VACV), human parainfluenza virus type 3 (HPIV-3), hepatitis B virus (HBV), and monkeypox virus (MPV). It was reported that smaller the size of AgNPs the more the inhibition efficacy.

Antibacterial Activity

Silver has been widely used since antiquity as a therapeutic agent for many diseases. Before the beginning of antibiotics therapy, silver was used for its antiseptic activity, specifically for the treatment of open wounds and burns. The potent antimicrobial activity against gram-positive and gram-negative bacteria, the low toxicity to mammalian cells at low concentrations, and the possibility of developing new generation antibiotics make AgNPs an attractive alternative to overcome the drug resistance problem. AgNPs have a high potential to solve the problem of multidrug-resistant bacteria because microorganisms are unlikely to develop resistance against silver as compared with antibiotics; in fact, silver attacks a broad range of targets in the microbes.

Many studies reported the direct damage of cell membranes as a principal mechanism of action of AgNPs; in fact, their adherence on the microbial cell wall may cause structural changes in the cell membrane and increase cell permeability leading to a powerful toxic effect that is related to the uncontrolled transport across cytoplasmic membrane. Electrostatic interactions are possibly implicated in the binding between negatively charged bacterial cell membranes and nanoparticles, but these interactions and the effect on the membrane integrity are directly dependent on size, shape and concentration of AgNPs.

It has been shown that the concentration of AgNPs that prevents bacterial growth is different for each type of bacterium. Pseudomonas aeruginosa and Vibrio cholerae were found to be more resistant than E. coli and Salmonella typhi. However, at concentrations above 75 µg/mL, bacterial growth was almost completely abolished for all of them. The antimicrobial activity of AgNPs against E. coli and Staphylococcus aureushsas been studied, and it was demonstrated that E. coli was inhibited at low concentration, whereas the growth inhibitory effects on S. aureus were less profound. Also reported is the antibacterial activity of different sizes of AgNPs against gram-positive (S. aureus) and gram-negative bacteria (Salmonella typhimurium). It has also been shown that the antibacterial activities of AgNPs can be modified by controlling the size of nanoparticles; in fact, the activity of AgNPs decreases with the increase in the particle size.

A different mechanism of antibacterial action of AgNPs postulated the generation of ROS (Reactive Oxygen Species) and the formation of free radicals, which induce membrane damage and have potent bactericidal activity. But of paramount importance is the ability of AgNPs to interfere with the bacterial replication process by adhering to their DNA or RNA. Ag+ interacts strongly with thiol groups in vital enzymes and with the phosphorus-containing bases of the DNA The interaction with the DNA bases may prevent cell division and DNA replication, leading to cell death.

Antifungal Activity

Apart from the antibacterial activity, antifungal activity of AgNPs was also extensively studied and these nanoparticles were found to be equally effective against wide range of plants as well human pathogenic fungi. Many reports are available in the literature but the present study was focused on some recent and significant studies. For example, it has been shown that the antifungal potential of biosynthesized AgNPs against some common fungal pathogens such as Phoma glomerata, P. herbarum, Fusarium semitectum, Trichoderma sp., and C. albicans. AgNPs were found to be effective against all these test fungi. Another study has shown effects against plant pathogenic fungi, in the activity of AgNPs against Aspergillus niger, A. foetidus, A. flavus, A. oryzae, A. parasiticus, and F. oxysporum. Furthermore, Candida species are highly pathogenic and involved in various infections including most important urinary tract infection. In addition, many species have been reported to be resistant to many commonly used antifungal agents. AgNPs can be the appropriate agents for the control of three Candida species, namely, C. albicans, C. tropicalis,
and C. krusei.

Parasitic Infections

Apart from the the therapeutical uses of AgNPs in cancer, bacterial, and viral diseases, AgNPs have also showed an important role against parasitic diseases. The parasitic diseases such as malaria, leishmaniasis, and trypanosomiasis are life threatening diseases and represent a significant global burden. The control and management of these diseases represent a challenge for scientists working in the field of drug discovery because of their devious nature and the ineffectiveness of available drug therapies. One study looked at the antileishmanial activity of AgNPs against Leishmania tropica parasites. Leishmaniasis is increasing rapidly worldwide, and unfortunately antileishmanial drugs have several disadvantages. Therefore, AgNPs could be the alternative to treat leishmaniasis.

References

Santos, A. Seckler, M. Ingle, A. Gupta, I. Galdiero, S. Galdiero, M. Gade, A. and Rai, M. 2014. Silver Nanoparticles: Therapeutical Uses, Toxicity, and Safety Issues. Journal of Pharmaceutical Sciences 103(7), pp.1931-1944.

Journal of Pharmaceutical Sciences antiviral and antibiotic studies of nanosilver particles
Volume 103, Issue 7, July 2014

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