Silver nanoparticle-based antimicrobials can promote a long lasting bactericidal effect without detrimental toxic side effects. However, there is not a clear and complete protocol to define and relate the properties of the particles (size, shape, surface charge, ionic content) with their specific activity. In this paper, we propose an effective multi-step approach for the identification of a ‘purpose-specific active applicability window’ to maximize the antimicrobial activity of medical devices containing silver nanoparticles (Ag NPs) (such as surface coaters), minimizing any consequent risk for human health (safety by design strategy). The antimicrobial activity and the cellular toxicity of four types of Ag NPs, differing in their coating composition and concentration have been quantified. Through the implementation of flow-field flow fractionation, Ag NPs have been characterized in terms of metal release, size and shape. The particles are fractionated in the process while being left unmodified, allowing for the identification of biological particle-specific contribution. Toxicity and inflammatory response in vitro have been assessed on human skin models, while antimicrobial activity has been monitored with both non-pathogenic and pathogenic Escherichia coli . The main benefit associated with such approach is the comprehensive assessment of the maximal effectiveness of candidate nanomaterials, while simultaneously indexing their properties against their safety.

Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment. Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C x T protocol). The dose is expressed as 6 hour-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3 and 13.2 mg/m³ CuO NPs, with a primary particle size of 10 9.2-14 nm and an MMAD of 1.5 µm. Twenty four hours after a 5-day exposure, dose-dependent lung inflammation and cytotoxicity was observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium and emphysema in the lung starting at 2.4 mg/m³. After a recovery period of 22 days, limited inflammation was still observed, but only at the highest dose of 13.2 mg/m³. The olfactory epithelium in the nose degenerated twenty four hours after exposure to 6.3 and 13.2 mg/m³, but this was restored after 22 days. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver. In conclusion, a 5-day, 6-hour/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period.