Nanoparticles (NPs) assumed an important role in the area of drug delivery. Despite the number of studies including NPs are growing over the last years, their side effects on the immune system are often ignored or omitted. One of the most studied polymers in the nano based drug delivery system field is chitosan (Chit). In the scientific literature, although the physicochemical properties [molecular weight (MW) or deacetylation degree (DDA)] of the chitosan, endotoxin contamination and appropriate testing controls are rarely reported, they can strongly influence immunotoxicity results. The present work aimed to study the immunotoxicity of NPs produced with different DDA and MW Chit polymers and to benchmark it against the polymer itself. Chit NPs were prepared based on the ionic gelation of Chit with sodium tripolyphosphate (TPP). This method allowed the production of two different NPs: Chit 80% NPs (80% DDA) and Chit 93% NPs (93% DDA). In general, we found greater reduction in cell viability induced by Chit NPs than the respective Chit polymers when tested in vitro using human peripheral blood monocytes (PBMCs) or RAW 264.7 cell line. In addition, Chit 80% NPs were more cytotoxic for PBMCs, increased reactive oxygen species (ROS) production (above 156 µg/mL) in the RAW 264.7 cell line and interfered with the intrinsic pathway of coagulation (at 1 mg/mL) when compared to Chit 93% NPs. On the other hand, only Chit 93% NPs induced platelet aggregation (at 2 mg/mL). Although Chit NPs and Chit polymers did not stimulate the nitric oxide (NO) production in RAW 264.7 cells, they induced a decrease in lipopolysaccharide (LPS)-induced NO production at all tested concentrations. None of Chit NPs and polymers caused hemolysis, nor induced PBMCs to secrete TNF-α and IL-6 cytokines. From the obtained results we concluded that the DDA of the Chit polymer and the size of Chit NPs influence the in vitro immunotoxicity results. As the NPs are more cytotoxic than the corresponding polymers, one should be careful in the extrapolation of trends from the polymer to the NPs, and in the comparisons among delivery systems prepared with different DDA chitosans.

With the COVID-19 pandemic, wearing facemasks became common. Many initiatives arose to develop new types of reusable textile masks in order to overcome a shortage of surgical masks for the health care personnel and for the civil society. Having such high demand of facemasks raises the question about what factors define their environmental sustainability. This paper presents a first simplified Life-Cycle-Assessment (LCA) comparing surgical masks and 2-layered cotton masks. The aim of the paper is to identify and understand the relevant ecological factors in order to support decision making on how textile masks could be designed in a more sustainable manner. The results of our simplified LCA show that the cotton masks were performing better than the surgical masks and vice versa depending on the environmental impact that was looked at. It was also found that the lifespan and the weight of the cotton masks are two variables having a great importance for their overall environmental performance.

The physicochemical properties of nanobiomaterials, such as their small size and high surface area ratio, make them attractive, novel drug-carriers, with increased cellular interaction and increased permeation through several biological barriers. However, these same properties hinder any extrapolation of knowledge from the toxicity of their raw material. Though, as suggested by the Safe-by-Design (SbD) concept, the hazard assessment should be the starting point for the formulation development. This may enable us to select the most promising candidates of polymeric nanobiomaterials for safe drug-delivery in an early phase of innovation. Nowadays the majority of reports on polymeric nanomaterials are focused in optimizing the nanocarrier features, such as size, physical stability and drug loading efficacy, and in performing preliminary cytocompatibility testing and proving effectiveness of the drug loaded formulation, using the most diverse cell lines. Toxicological studies exploring the biological effects of the polymeric nanomaterials, particularly regarding immune system interaction are often disregarded. The objective of this review is to illustrate what is known about the biological effects of polymeric nanomaterials and to see if trends in toxicity and general links between physicochemical properties of nanobiomaterials and their effects may be derived. For that, data on chitosan, polylactic acid (PLA), polyhydroxyalkanoate (PHA), poly(lactic-co-glycolic acid) (PLGA) and policaprolactone (PCL) nanomaterials will be evaluated regarding acute and repeated dose toxicity, inflammation, oxidative stress, genotoxicity, toxicity on reproduction and hemocompatibility. We further intend to identify the analytical and biological tests described in the literature used to assess polymeric nanomaterials toxicity, to evaluate and interpret the available results and to expose the obstacles and challenges related to the nanomaterial testing. At the present time, considering all the information collected, the hazard assessment and thus also the SbD of polymeric nanomaterials is still dependent on a case-by-case evaluation. The identified obstacles prevent the identification of toxicity trends and the generation of an assertive toxicity database. In the future, in vitro and in vivo harmonized toxicity studies using unloaded polymeric nanomaterials, extensively characterized regarding their intrinsic and extrinsic properties should allow to generate such database. Such a database would enable us to apply the SbD approach more efficiently.

Injection of nanoparticles (NP) into the bloodstream leads to the formation of a so-called “nano–bio” interface where dynamic interactions between nanoparticle surfaces and blood components take place. A common consequence is the formation of the protein corona, that is, a network of adsorbed proteins that can strongly alter the surface properties of the nanoparticle. The protein corona and the resulting structural changes experienced by adsorbed proteins can lead to substantial deviations from the expected cellular uptake as well as biological responses such as NP aggregation and NP-induced protein fibrillation, NP interference with enzymatic activity, or the exposure of new antigenic epitopes. Achieving a detailed understanding of the nano–bio interface is still challenging due to the synergistic effects of several influencing factors like pH, ionic strength, and hydrophobic effects, to name just a few. Because of the multiscale complexity of the system, modeling approaches at a molecular level represent the ideal choice for a detailed understanding of the driving forces and, in particular, the early events at the nano–bio interface. This review aims at exploring and discussing the opportunities and perspectives offered by molecular modeling in this field through selected examples from literature.

This review aims to elucidate the current knowledge and future research needs regarding the hazard potential of nanocellulose to human health. Growing interest from research and industry alike has led to increasing likelihood of human contact to the material via various exposure routes. Although a number of comprehensive reviews on human health hazards of nanocellulose have been conducted, this paper brings new insights as it systematically analyzes and quantitatively assesses the results of in vivo and in vitro tests in terms of investigated endpoints, tested concentration ranges, physicochemical properties, surface modifications and source of the tested nanocellulose, exposure route, and cell lines used. The quality of the studies is further inspected based on various established criteria. Considering the rapid development of nanocellulose-based products and the novelty of the material, human health studies remain scarce. By assessing those that have been conducted, patterns and gaps were identified that will be helpful to guide future research. The results show that there are still significant uncertainties remaining, particularly regarding in vivo testing, with pulmonary exposure showing some cause for concern. Although a substantial number of in vitro studies have been undertaken, results are often conflicting. The detected effects could not be directly attributed to size of nanoparticles, cell lines, surface modifications or tested concentrations. This may also be linked to the varying quality of the studies. This review ends by identifying key gaps to help pave the way for future research and ensure the safe development and use of nanocellulose.