Design strategies supporting the development of antiviral nano-Ag-based materials under a SSbD approach

Safe and sustainable by design (SSbD) is an approach to materials and products design that should match functionality, safety and overall sustainability criteria throughout their lifecycle. To achieve the goal two main areas of expertise are involved: on one side, design strategies, methodologies and techniques, inspired by green chemistry and eco-design principles, and on the other side a robust framework to assess the SSbD performance attributes, in a life-cycle perspective. This challenge is particularly tricky when the materials are nanometric and designed to be bio-active, like the case of antimicrobial solutions, which should be selective for their intended targets (microorganisms) but have minimal effects on off-target human cells or ecosystems. To compare design solutions and get a quick idea of their potential efficacy, drug-discovery research provides us an indicator, the selectivity index, defined as the ratio of the concentration of a drug required to produce toxicity in 50% of cells (CC50) to the concentration of the drug required to produce a desired pharmacological effect in 50% of cells (EC50). Silver nanoparticles (nano-Ag) have been known for their antimicrobial properties for a long time, but the COVID-19 pandemic has generated renewed interest in their potential applications as well as new concerns for their use in some biocidal products. Unfortunately, this interest has also led to the proliferation of fraudulent and uncertified products in the market, which may be unsafe for use. So developing design solutions and guiding principles [1] that match SSbD criteria is of technological and methodological extreme importance. In this work, we present some Ag-based design alternatives developed to promote their SSbD use in antiviral applications. In agreement with eco-design and green chemistry principles, AgNPs were nucleated in water, at room temperature, using biogenic reducing/capping agents (curcumin, sodium surfactin, hydroxyethylcellulose). To explore the design space and identify the best SSbD solutions, we modified the main synthesis parameters and the type of capping agent in line with a design of experiment (DoE) approach. A widespread characterization was performed (DLS/ELS, TEM, XRD, UV-VIS, XPS) to assess the physicochemical properties (design variables space) affecting technical and functional performances (design performance attributes), to make some mechanistic hypothesis and derive SSbD driving principles applicable to AgNPs synthesis. The calculation of the selectivity index by assessing the cytotoxicity (Vero cells) and antiviral properties (SARs CoV 2 virus) allowed us to make a first screening for the selection of materials most promising under an SSbD approach. The results pointed out an actual enhanced risk/benefit profile of the proposed Ag-based solutions, particularly for curcumin-capped AgNPs, with respect to commercial alternatives or even with respect to antiviral drugs considered at the beginning of Covid pandemia such as chloroquine.