In vitro skin toxicity of CuO and ZnO nanoparticles: Application in the safety assessment of antimicrobial coated textiles

In the context of nosocomial infections, there is an urgent need to develop efficient nanomaterials (NMs) with antibacterial properties for the prevention of infection diseases. Metal oxide nanoparticles (MeO-NPs) are promising candidates for the development of new antibacterial textiles. However, the direct exposure to MeO-NPs and MeO-coated NMs through skin contact could constitute a severe hazard for human health. In this work, the toxicity of copper and zinc oxide (CuO, ZnO) NPs antimicrobial-coated textiles was assessed on an in vitro reconstructed 3D model of epidermis. Thus, MeO-NPs and extracts from MeO-coated NMs were tested on EpiDerm™ skin model according to OECD TG 431 (Corrosion Test) and 439 (Irritation Test), respectively. Skin surface fluids composition is a crucial aspect to be considered in the development of NMs that have to encounter this tissue. So, for the irritation test, coated textiles were extracted in artificial sweat solutions at pH 4.7 and 6.5. Skin tissue viability, pro-inflammatory interleukin-8 secretion and morphological alteration of intermediate and actin filaments of keratinocytes were evaluated after 18 h exposure to extracts from CuO- and ZnO-coated textiles. Analysis of extracts at the two pH conditions indicated that released ions and not NPs are involved in promoting adverse effects on epidermis. Since Cu2+ and Zn2+ ions are known to penetrate epidermis, Balb/3 T3 cells were used as model of dermis. Fibroblasts viability was investigated after the exposure to trans-epidermis permeated ions, collected from EpiDerm™ basal supernatants, and to extracts, as representative of a direct interaction of ions with dermis cells by wounded skin. From our data we can conclude that: 1) skin surface fluids composition is a key parameter for the stability of NPs-coated textiles; 2) MeO ions released from coated textiles can deeply affect the epidermal tissue and the underlying dermal cells upon trans-epidermal permeation; 3) skin barrier integrity is a fundamental prerequisite that should be taken into account during the assessment of NMs safety by direct contact exposure.