Bacterial infection from medical devices is a major problem and accounts for an increasing number of deaths as well as high medical costs. Many different strategies have been developed to decrease the incidence of medical device related infection. One way to prevent infection is by modifying the surface of the devices in such a way that no bacterial adhesion can occur. This requires modification of the complete surface with, mostly, hydrophilic polymeric surface coatings. These materials are designed to be non-fouling, meaning that protein adsorption and subsequent microbial adhesion are minimized. Incorporation of antimicrobial agents in the bulk material or as a surface coating has been considered a viable alternative for systemic application of antibiotics. However, the manifestation of more and more multi-drug resistant bacterial strains restrains the use of antibiotics in a preventive strategy. The application of silver nanoparticles on the surface of medical devices has been used to prevent bacterial adhesion and subsequent biofilm formation. The nanoparticles are either deposited directly on the device surface, or applied in a polymeric surface coating. The silver is slowly released from the surface, thereby killing the bacteria present near the surface. In the last decade there has been a surplus of studies applying the concept of silver nanoparticles as an antimicrobial agent on a range of different medical devices. The main problem however is that the exact antimicrobial mechanism of silver remains unclear. Additionally, the antimicrobial efficacy of silver on

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New Strategies in the Development of Antimicrobial Coatings: The Example of Increasing Usage of Silver and Silver Nanoparticles

Implant-associated infection is a major source of morbidity in orthopaedic surgery. There has been extensive research into the development of materials that prevent biofilm formation, and hence, reduce the risk of infection. Silver nanoparticle technology is receiving much interest in the field of orthopaedics for its antimicrobial properties, and the results of studies to date are encouraging. Antimicrobial effects have been seen when silver nanoparticles are used in trauma implants, tumour prostheses, bone cement, and also when combined with hydroxyapatite coatings. Although there are promising results with in vitro and in vivo studies, the number of clinical studies remains small. Future studies will be required to explore further the possible side effects associated with silver nanoparticles, to ensure their use in an effective and biocompatible manner. Here we present a review of the current literature relating to the production of nanosilver for medical use, and its orthopaedic applications.

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Silver nanoparticles and their orthopaedic applications

Bacteria and superbugs have become more resistant to several antibiotics. Continuous and overuse of such antibiotics led to outbreaks of superbugs in both hospitals and communities. In recent decades, silver was used in medical treatment such as burns, wounds and bacterial infections. Silver metallic, silver nitrate and silver sulfadiazine were utilized for this treatment. Nowadays, silver nanoparticles and silver ions are effectively used as antibacterial agents in the medical field in the form of nanoparticles and ions, where silver ions proved an effective antimicrobial against active bacteria, viruses, and fungi than silver nanoparticles Ag NPs. However, modified or functionalized silver NPs are extremely active to kill bacteria than pure Ag NPs. Silver nanoparticle's size, shape, and concentration play an important role in their antimicrobial activities.

https://link.springer.com/content/pdf/10.1007/s10904-020-01744-x.pdf

Silver Nanoparticles and Silver Ions as Potential Antibacterial Agents

Supramolecular medicinal chemistry field has been a quite rapidly developing, increasingly active and newly rising interdiscipline which is the new expansion of supramolecular chemistry in pharmaceutical sciences, and is gradually becoming a relatively independent scientific area. Supramolecular drugs could be defined as medicinal supermolecules formed by two or more molecules through non-covalent bonds. So far a lot of supermolecules as chemical drugs have been widely used in clinics. Supermolecules as chemical drugs, i.e. supramolecular chemical drugs or supramolecular drugs, which might have the excellences of lower cost, shorter period, higher potential as clinical drugs for their successful research and development, may possess higher bioavailability, better biocompatibility and drug-targeting, fewer multidrug-resistances, lower toxicity, less adverse effect, and better curative effects as well as safety, and therefore exhibit wide potential application. These overwhelming advantages have drawn enormous special attention. This paper gives the definition of supramolecular drugs, proposes the concept of supramolecular chemical drugs, and systematically reviews the recent advances in the research and development of supermolecules, including organic and inorganic complex ones as chemical drugs in the area of antitumor, anti-inflammatory, analgesic, antimalarial, antibacterial, antifungal, antivirus, anti-epileptic, cardiovascular agents and magnetic resonance imaging agents and so on. The perspectives of the foreseeable future and potential application of supramolecules as chemical drugs are also presented.

https://link.springer.com/content/pdf/10.1007%2Fs11426-009-0103-2.pdf

Review on supermolecules as chemical drugs

The new series of silver(I) coordination polymers [Ag(N–N)(μ-PTA)]n(X)n (1, 2, 4–8, 10, 11) and discrete monomers [Ag(N–N)(PTA)2](X) (3, 9) {N–N = bpy (1–3), dtbpy (4), neocup (5, 6), phen (7–9), dione (10, 11); X = NO3 (1, 3, 5, 7, 9, 10), PF6 (2, 4, 6, 8, 11)} were generated by self-assembly reactions, in MeOH at ∼25 °C, of AgNO3 or AgPF6 with 1,3,5-triaza-7-phosphaadamantane (PTA) and the corresponding polypyridines, namely 2,2′-bipyridine (bpy), 4,4′-di-tert-butyl-2,2′-bipyridine (dtbpy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neocup) and 1,10-phenanthroline-5,6-dione (dione). The compounds were obtained as air and light stable solids and characterized by IR, 1H and 31P{1H} NMR spectroscopy, ESI+-MS and elemental analyses. The crystal structure of 1 was determined by single crystal X-ray diffraction analysis, revealing infinite one-dimensional (1D) linear chains driven by μ-PTA N,P-linkers. Apart from representing the first examples of the metal–PTA derivatives bearing polypyridine ligands, 1–11 also feature solubility in water (S25°C ≈ 4–18 mg mL−1). Selected compounds (1, 3, 5, 7, 9 and 10) were thus tested for their biological properties and found to exhibit significant antibacterial and antifungal activities, screened in vitro against the standard strains of Staphylococcus aureus, Staphylococcus pyogenes, Staphylococcus pneumoniae, Staphylococcus sanguinis, Staphylococcus mutans, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. Furthermore, the compounds 5, 7, 9 and 10 show a pronounced antiproliferative activity against human malignant melanoma (A375), and the effects on the inhibition of tumor cells in vitro are in agreement with the DNA-binding studies.

New water-soluble polypyridine silver(I) derivatives of 1,3,5-triaza-7-phosphaadamantane (PTA) with significant antimicrobial and antiproliferative activities

Synthesis, X-ray structure and antimycobacterial activity of silver complexes with α-hydroxycarboxylic acids

The present work describes the synthesis and antimycobacterial activity of three Ag(I)-complexes with the sweeteners aspartame, saccharin, and cyclamate as ligands, with the aim of finding new candidate substances for fighting tuberculosis and other mycobacterial infections. The minimal inhibitory concentration of these three complexes was investigated in order to determine their in-vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium malmoense, and Mycobacterium kansasii. The MIC values were determined using the Microplate Alamar Blue Assay. The best MIC values found for the complexes were 9.75 μM for Ag(I)-aspartame against M. kansasii and 15.7 μM for Ag(I)-cyclamate against M. tuberculosis.

Synthesis, characterization and antimycobacterial activity of Ag(I)-aspartame, Ag(I)-saccharin and Ag(I)-cyclamate complexes.

The history of Mycobacterium tuberculosis (MTB) as the main agent of tuberculosis (TB) goes back a very long time. Fragments of the spinal column of Egyptian mummies from 2400 BCE (Before Common Era) show definite pathological signs of tubercular decay (Tripathi, Tewari et al., 2005). From that time to the present day millions have died of the disease and only a few drugs are active against the bacilli. Current data show an ancient disease more prevalent in the world today than at any other time in human history (Koul, Arnoult et al., 2011). Annually, TB is responsible for the death of two to three million people worldwide and global economic losses around $ 12 billion (Ma, Lienhardt et al., 2010). Approximately a third of the world’s population is estimated to be infected with MTB, giving rise to 9.4 million new cases of active TB disease each year (Zwerling, Behr et al., 2011). In addition, the highly resistant Multi-Drug-resistant (MDR) and Extensively-Drug-Resistant (XDR) MTB organisms are virtually untreatable in immunocompetent patients. So when these bacteria enter into contact with highly immunocompromised HIV-infected populations, the mortality rate reaches 100% within a few weeks of infection (Gandhi, Nunn et al., 2010).

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Daisy N. Sato

Papers

Synthesis, X-ray structure and antimycobacterial activity of silver complexes with α-hydroxycarboxylic acids

Synthesis, characterization and antimycobacterial activity of Ag(I)-aspartame, Ag(I)-saccharin and Ag(I)-cyclamate complexes.

An Approach to the Search for New Drugs Against Tuberculosis