Historically silver salts have been used for infections such as syphilis and gonorrhea (3) and nowadays the use of silver has extended to treat a range of other microorganism including human pathogens. Recently, due to the advancement of nanotechnology, size-controlled silver nanoparticles have been produced in a large scale at industrial sites or laboratories, which has leads to the wide application of silver nanoparticles as broad spectrum antimicrobial agents. Contrary to the effects of ionic silver, the antimicrobial activity of silver particles is determined by the dimensions of the particles. Small particles have greater antimicrobial effect than large particles. One recent paper shows that the minimum inhibitory concentration (MIC) of silver nanoparticles (mean diameter of 9 nm) against Gram positive S. aureus and Gram negative Escherichia coli were 180 µg/ml and 15 µg/ml, respectively (4). When compared, silver sulfadiazine silver nanoparticles were more effective with a significantly lower risk for percutaneous absorption of silver ions (5). The other report shows that the MIC of smaller silver nanoparticles (mean diameter of 9~14 nm) have lower MIC (14~28 µg/ml) to E. coli, Pseudomonas aeruginosa and S. aureus than those of larger particles (mean diameter of 24~30 nm), which are 215~258 µg/ml (6). But the assay methods also influence the bactericidal activities. When the same 10 nm silver nanoparticles were used, E. coli was more sensitive than Bacillus subtilis in the growth inhibition and colony forming unit (CFU) assays, whereas B. subtilis was more sensitive than E. coli in the liquid-to-plate assay (7).

The exact mechanisms of antimicrobial or toxicity activities by silver nanoparticles are still in investigation. The positive charge on the Ag ion is suggested crucial for antimicrobial activity. Some literature shows that the electrostatic attraction between negatively charged bacterial cells and positively charged nanoparticles is responsible (8). These nanoparticles have been shown to accumulate inside the membrane and can subsequently penetrate into the cells causing damage of cell wall or cell membranes (9). Other mechanisms involving interaction of silver molecules with biological macromolecules such as enzymes and DNA through an electron-release mechanism (10) or free radical production (11) have been proposed. Some literatures suggest inhibition of cell wall synthesis as well as protein synthesis has been shown to be induced by silver nanoparticles with the proteomic data showing evidence of accumulation of envelope protein precursor or destabilization of outer membrane, which finally leads to ATP leaking (12).

During the past decade, the application of silver nanoparticles in wound dressing has dramatically increased as a preferred treatment for infected wounds, including burn wounds (13, 14). Silver infused wound dressing shows efficient bactericidal activities against routine isolates from burn wounds. Forty-nine antibiotic-resistant bacteria including vancomycin-resistant Enterococcus faecium, methicillin-resistant S. aureus, multidrug-resistant (MDR) P. aeruginosa, MDR Vibrio spp., extended-spectrum β-lactamase producing Salmonella spp., ESBL producing Klebsiella pneumoniae, ESBL producing Proteus mirabilis, ESBL producing E. coli and MDR Acinetobacter baumannii show susceptibility to the antimicrobial activities over all pH ranges although all of which are more susceptible in instances of higher pH acidity levels (15). Some dressings have been modified to work more efficiently. A biological dressing containing silver-impregnated polyelectrolyte multilayers was revealed to reduce bacterial burdens significantly in murine skin wounds (16). Dressings with chitosan-based composite sponge containing silver nanoparticles have also proven to possess bacteriostatic and bactericidal properties against S. aureus, E. coli and P. aeruginosa (17). Furthermore biocomposite films composed of chitosan sago starch and silver nanoparticles showed faster healing patterns compared to the untreated control, which suggests that this film may be applicable not only as a dressing material for wound healing but also for bactericidal purpose (18). These wound healing results are supported by our report that silver nanoparticles induce angiogenesis with induction of vascular endothelial growth factor and nitric oxide in the animal model (19). Some silver nanoparticles are more effectively modified when prepared in thermosensitive gel (20) or in a disc carrier (21) to improve their medical applications.

In addition to their antibacterial activities, silver nanoparticles are also reported to have antiviral properties. Silver nanoparticles are known to bind envelope protein gp120 of human immunodeficiency virus to interfere viral binding to CD4⁺ T cells (22). Silver nanoparticles also bind extracellular virions of hepatitis B viruses or inhibit RNA synthesis of these viruses (23). The inhibitory effect of silver nanoparticles for replication of influenza virus by inhibiting fusion of viral membranes (24) and inhibition of early phase replication of Tacaribe virus (25) have also been reported.

In conclusion, the importance of silver nanoparticles is clearly demonstrated by their broad-spectrum antimicrobial activity; their wide application as a topical agent applied to cervical tissues or to mucous membrane is also promising.