Thiazolide Prodrug Esters and Derived Peptides: Synthesis and Activity.

Amino acid ester prodrugs of the thiazolides, introduced to improve the pharmacokinetic parameters of the parent drugs, proved to be stable as their salts but were unstable at pH > 5. Although some of the instability was due to simple hydrolysis, we have found that the main end products of the degradation were peptides formed by rearrangement. These peptides were stable solids: they maintained significant antiviral activity, and in general, they showed improved pharmacokinetics (better solubility and reduced clearance) compared to the parent thiazolides. We describe the preparation and evaluation of these peptides.

Biologically produced nanosilver: current state and future perspectives.

Silver nanoparticles are one of the most commercialized nanomaterials. They are widely applied as biocides for their strong antimicrobial activity, but also their conductive, optic and catalytic properties make them wanted in many applications. The chemical and physical processes which are used to synthesize silver nanoparticles generally have many disadvantages and are not eco-friendly. In this review, we will discuss biological alternatives that have been developed using microorganisms or plants to produce biogenic silver. Until now, only their antimicrobial activity has been studied more into detail. In contrast, a wide range of practical applications as biocide, biosensor, and catalyst are still unexplored. The shape, size, and functionalization of the nanoparticles is defined by the biological system used to produce the nanoparticles, hence for every application a specific biological production process needs to be chosen. On the other hand, biogenic silver needs to compete with chemically produced nanosilver on the market. Large scale production generating inexpensive nanoparticles is needed. This can only be achieved when the biological production system is chosen in function of the yield. Hence, the true challenge for biogenic silver is finding the balance between scalability, price, and applicability.

The antibacterial activity of biogenic silver and its mode of action.

In a previous study, biogenic silver nanoparticles were produced by Lactobacillus fermentum which served as a matrix preventing aggregation. In this study the antibacterial activity of this biogenic silver was compared to ionic silver and chemically produced nanosilver. The minimal inhibitory concentration (MIC) was tested on Gram-positive and Gram-negative bacteria and was comparable for biogenic silver and ionic silver ranging from 12.5 to 50 mg/L. In contrast, chemically produced nanosilver had a much higher MIC of at least 500 mg/L, due to aggregation upon application. The minimal bactericidal concentration (MBC) in drinking water varied from 0.1 to 0.5 mg/L for biogenic silver and ionic silver, but for chemically produced nanosilver concentrations, up to 12.5 mg/L was needed. The presence of salts and organic matter decreased the antimicrobial activity of all types of silver resulting in a higher MBC and a slower inactivation of the bacteria. The mode of action of biogenic silver was mainly attributed to the release of silver ions due to the high concentration of free silver ions measured and the resemblance in performance between biogenic silver and ionic silver. Radical formation by biogenic silver and direct contact were found to contribute little to the antibacterial activity. In conclusion, biogenic nanosilver exhibited equal antimicrobial activity compared to ionic silver and can be a valuable alternative for chemically produced nanosilver.

Biogenic silver for disinfection of water contaminated with viruses.

The presence of enteric viruses in drinking water is a potential health risk. Growing interest has arisen in nanometals for water disinfection, in particular the use of silver-based nanotechnology. In this study, Lactobacillus fermentum served as a reducing agent and bacterial carrier matrix for zerovalent silver nanoparticles, referred to as biogenic Ag(0). The antiviral action of biogenic Ag(0) was examined in water spiked with an Enterobacter aerogenes-infecting bacteriophage (UZ1). Addition of 5.4 mg liter(-1) biogenic Ag(0) caused a 4.0-log decrease of the phage after 1 h, whereas the use of chemically produced silver nanoparticles (nAg(0)) showed no inactivation within the same time frame. A control experiment with 5.4 mg liter(-1) ionic Ag+ resulted in a similar inactivation after 5 h only. The antiviral properties of biogenic Ag(0) were also demonstrated on the murine norovirus 1 (MNV-1), a model organism for human noroviruses. Biogenic Ag(0) was applied to an electropositive cartridge filter (NanoCeram) to evaluate its capacity for continuous disinfection. Addition of 31.25 mg biogenic Ag(0) m(-2) on the filter (135 mg biogenic Ag(0) kg(-1) filter medium) caused a 3.8-log decline of the virus. In contrast, only a 1.5-log decrease could be obtained with the original filter. This is the first report to demonstrate the antiviral efficacy of extracellular biogenic Ag(0) and its promising opportunities for continuous water disinfection.

Lactic acid bacteria as reducing and capping agent for the fast and efficient production of silver nanoparticles.

There is a growing demand for silver-based biocides, including both ionic silver forms and metallic nanosilver. The use of metallic nanosilver, typically chemically produced, faces challenges including particle agglomeration, high costs, and upscaling difficulties . Additionally, there exists a need for the development of a more eco-friendly production of nanosilver. In this study, Gram-positive and Gram-negative bacteria were utilized in the non-enzymatic production of silver nanoparticles via the interaction of silver ions and organic compounds present on the bacterial cell. Only lactic acid bacteria, Lactobacillus spp., Pediococcus pentosaceus, Enterococcus faecium, and Lactococcus garvieae, were able to reduce silver. The nanoparticles of the five best producing Lactobacillus spp. were examined more into detail with transmission electron microscopy. Particle localization inside the cell, the mean particle size, and size distribution were species dependent, with Lactobacillus fermentum having the smallest mean particle size of 11.2 nm, the most narrow size distribution, and most nanoparticles associated with the outside of the cells. Furthermore, influence of pH on the reduction process was investigated. With increasing pH, silver recovery increased as well as the reduction rate as indicated by UV-VIS analyses. This study demonstrated that Lactobacillus spp. can be used for a rapid and efficient production of silver nanoparticles.