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Campylobacter is a virulent Gram-negative bacterial genus mainly found in the intestines of poultry. The indiscriminate use of traditional antibiotics has led to drug resistance in these pathogens, necessitating the development of more efficient and less toxic therapies. Despite their complex biologically active structures, the clinical applications of essential oils (EOs) remain limited. Therefore, this study aimed to increase the bioavailability, stability, and biocompatibility and decrease the photodegradation and toxicity of EO using nanotechnology. The diffusion disk test revealed the potent anti-Campylobacter activity of cinnamon, lemongrass, clove, geranium, and oregano EOs (>50 mm). These were subsequently used to prepare nanostructured lipid carriers (NLCs). Formulations containing these EOs inhibited Campylobacter spp. growth at low concentrations (0.2 mg/mL). The particle size, polydispersity index, and zeta potential of these systems were monitored, confirming its physicochemical stability for 210 days at 25 °C. FTIR-ATR and DSC analyses confirmed excellent miscibility among the excipients, and FE-SEM elucidated a spherical shape with well-delimited contours of nanoparticles. The best NLCs were tested regarding nanotoxicity in a chicken embryo model. These results indicate that the NLC-based geranium EO is the most promising and safe system for the control and treatment of multidrug-resistant strains of Campylobacter spp.

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Superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention in biomedical research due to their potential applications. However, little is known about their impact and toxicity on testicular cells. To address this issue, we conducted an in vitro study using primary mouse testicular cells, testis fragments, and sperm to investigate the cytotoxic effects of sodium citrate-coated SPIONs (Cit_SPIONs). Herein, we synthesized and physiochemically characterized the Cit_SPIONs and observed that the sodium citrate diminished the size and improved the stability of nanoparticles in solution during the experimental time. The sodium citrate (measured by thermogravimetry) was biocompatible with testicular cells at the used concentration (3%). Despite these favorable physicochemical properties, the in vitro experiments demonstrated the cytotoxicity of Cit_SPIONs, particularly towards testicular somatic cells and sperm cells. Transmission electron microscopy analysis confirmed that Leydig cells preferentially internalized Cit_SPIONs in the organotypic culture system, which resulted in alterations in their cytoplasmic size. Additionally, we found that Cit_SPIONs exposure had detrimental effects on various parameters of sperm cells, including motility, viability, DNA integrity, mitochondrial activity, lipid peroxidation (LPO), and ROS production. Our findings suggest that testicular somatic cells and sperm cells are highly sensitive and vulnerable to Cit_SPIONs and induced oxidative stress. This study emphasizes the potential toxicity of SPIONs, indicating significant threats to the male reproductive system. Our findings highlight the need for detailed development of iron oxide nanoparticles to enhance reproductive nanosafety.

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Polyethylene terephthalate (PET) is a commonly used thermoplastic in industry due to its excellent malleability and thermal stability, making it extensively employed in packaging manufacturing. Inadequate disposal of PET packaging in the environment and natural physical-chemical processes leads to the formation of smaller particles known as PET micro and nanoplastics (MNPs). The reduced dimensions enhance particle bioavailability and, subsequently, their reactivity. This study involved chemical degradation of PET using trifluoroacetic acid to assess the impact of exposure to varying concentrations of PET MNPs (0.5, 1, 5, 10, and 20 mg/L) on morphological, functional, behavioral, and biochemical parameters during the early developmental stages of zebrafish (Danio rerio). Characterization of the degraded PET revealed the generated microplastics (MPs) ranged in size from 1305 to 2032 µm, and that the generated nanoplastics (NPs) ranged from 68.06 to 955 nm. These particles were then used for animal exposure. After a six-day exposure period, our findings indicate that PET MNPs can diminish spontaneous tail coiling (STC), elevate the heart rate, accumulate on the chorion surface, and reduce interocular distance. These results suggest that PET exposure induces primary toxic effects on zebrafish embryo-larval stage of development.

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Since the discovery of the third allotropic carbon form, carbon-based one-dimensional nanomaterials (1D-CNMs) became an attractive and new technology with different applications that range from electronics to biomedical and environmental technologies. Despite their broad application, data on environmental risks remain limited. Fish are widely used in ecotoxicological studies and biomonitoring programs. Thus, the aim of the current study was to summarize and critically analyze the literature focused on investigating the bioaccumulation and ecotoxicological impacts of 1D-CNMs (carbon nanotubes and nanofibers) on different fish species. In total, 93 articles were summarized and analyzed by taking into consideration the following aspects: bioaccumulation, trophic transfer, genotoxicity, mutagenicity, organ-specific toxicity, oxidative stress, neurotoxicity and behavioral changes. Results have evidenced that the analyzed studies were mainly carried out with multi-walled carbon nanotubes, which were followed by single-walled nanotubes and nanofibers. Zebrafish (Danio rerio) was the main fish species used as model system. CNMs' ecotoxicity in fish depends on their physicochemical features, functionalization, experimental design (e.g. exposure time, concentration, exposure type), as well as on fish species and developmental stage. CNMs' action mechanism and toxicity in fish are associated with oxidative stress, genotoxicity, hepatotoxicity and cardiotoxicity. Overall, fish are a suitable model system to assess the ecotoxicity of, and the environmental risk posed by, CNMs.

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The exponential use of plastics has significantly increased environmental pollution by nanoplastics (NPs). In the aquatic environment, NPs interact and bioaccumulate in the biota, posing a potential ecotoxicological risk. The present study investigated the developmental toxicity, vasotoxicity, cytotoxicity, ROS induction, and behavioral impairments in zebrafish (Danio rerio) exposed to environmentally relevant polystyrene NPs (PS-NPs) concentrations (0.04, 34 ng L-1, and 34 µg L-1) for 144 h through multiple biomarkers response (mortality, frequency of spontaneous contractions, heart rate, and morphological changes). Furthermore, vasotoxicity (head, yolk sac, tail, and branchial vessels) was evaluated using the transgenic zebrafish tg(Fli1:eGFP). Results showed that PS-NPs interacted mainly with zebrafish chorion, gills, tail, and larvae head. PS-NPs at 34 ng L-1 and 34 µg L-1 induced neurotoxicity (decreased frequency of spontaneous contractions), cardiotoxicity (bradycardia), and morphological changes in the eyes and head, indicating that PS-NPs induce developmental impairments in zebrafish. In addition, cytotoxicity in the caudal region (34 ng L-1), ROS production, decreased mean swimming speed, and distance covered were observed in all tested concentrations. PS-NPs also induced vasotoxicity (yolk sac region) in transgenic zebrafish. Overall, the present study demonstrates the harmful effects of PS-NPs on the early developmental stages of freshwater fish, indicating their environmental risk.

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When silica nanoparticles (SiNP) reach the water bodies interact with the already existing pollutants in the environments. This study aimed to evaluate the ecotoxicity of SiNP under the presence/absence of Cu in mosquitofish (Gambusia holbrooki). Fish were exposed to 0, 10 and 100 mg SiNP L-1, alone or mixed with Cu (0.25 mg L-1). After 96 h, the amount of colony forming units (CFU) of bacteria living on the skin mucus was analysed, and oxidative stress, tissue damage enzymes, and neurotoxicity were evaluated. We observed a reduction in CFU when Cu was present in the media. The liver was the target organ, evidencing a decrease in tissue damage enzymatic activities, activation of the antioxidant system in all treatments, and lipid oxidative damage when the SiNP and Cu were mixed. Overall, SiNP ecotoxicity was proved, which could also be enhanced by the presence of ubiquitous elements such as metals.

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Nanomaterials such as titanium dioxide and magnetite are increasingly used in several fields, such as water remediation and agriculture. However, this has raised environmental concerns due to potential exposure to organisms like humans. Nanomaterials can cause adverse interactions depending on physicochemical characteristics, like size, morphology, and composition, when interacting with living beings. To ensure safe use and prevent the risk of exposure to nanomaterials, their biocompatibility must be assessed. In vitro cell cultures are beneficial for assessing nanomaterial-cell interactions due to their easy handling. The present study evaluated the biocompatibility of TiO2, Fe3O4, and TiO2/Fe3O4 nanomaterials thermally treated at 350 °C and 450 °C in erythrocytes and HepG2 cells. According to the hemolysis experiments, non-thermally treated NMs are toxic (>5% hemolysis), but their thermally treated counterparts do not present toxicity (<2%). This behavior indicates that the toxicity derives from some precursor (solvent or surfactant) used in the synthesis of the nanomaterials. All the thermally treated nanomaterials did not show hemolytic activity under different conditions, such as low-light exposure or the absence of blood plasma proteins. In contrast, non-thermally treated nanomaterials showed a high hemolytic behavior, which was reduced after the purification (washing and thermal treatment) of nanomaterials, indicating the presence of surfactant residue used during synthesis. An MTS cell viability assay shows that calcined nanomaterials do not reduce cell viability (>11%) during 24 h of exposure. On the other hand, a lactate dehydrogenase leakage assay resulted in a higher variability, indicating that several nanomaterials did not cause an increase in cell death as compared to the control. However, a holotomographic microscopy analysis reveals a high accumulation of nanomaterials in the cell structure at a low concentration (10 µg mL-1), altering cell morphology, which could lead to cell membrane damage and cell viability reduction.

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Titanium dioxide is a type of nanoparticle that is composed of one titanium atom and two oxygen atoms. One of its physicochemical activities is photolysis, which produces different reactive oxygen species (ROS). Atya lanipes shrimp affect detrital processing and illustrate the potential importance of diversity and nutrient availability to the rest of the food web. It is essential in removing sediments, which have an important role in preventing eutrophication. This study aimed to determine the toxic effect of changes in behavior and levels of oxidative stress due to exposure to titanium dioxide nanoparticles in Atya lanipes and to determine the effective concentration (EC50) for behavioral variables. The concentrations of TiO2 NPs tested were 0.0, 0.50, 1.0, 2.0, and 3.0 mg/L with the positive controls given 100 µg/L of titanium and 3.0 mg/L of TiO2 NPs ± 100 µg/L of titanium. After 24 h of exposure, significant hypoactivity was documented. The EC50 was determined to be a concentration of 0.14 mg/L. After the exposure to 10 mg/L of TiO2 NPs, oxidative stress in gastrointestinal and nervous tissues was documented. The toxic effects of this emerging aquatic pollutant in acute exposure conditions were characterized by sublethal effects such as behavior changes and oxidative stress.

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Nanotechnology-based strategies have played a pivotal role in innovative products in different technological fields, including medicine, agriculture, and engineering. The redesign of the nanometric scale has improved drug targeting and delivery, diagnosis, water treatment, and analytical methods. Although efficiency brings benefits, toxicity in organisms and the environment is a concern, particularly in light of global climate change and plastic disposal in the environment. Therefore, to measure such effects, alternative models enable the assessment of impacts on both functional properties and toxicity. Caenorhabditis elegans is a nematode model that poses valuable advantages such as transparency, sensibility in responding to exogenous compounds, fast response to perturbations besides the possibility to replicate human disease through transgenics. Herein, we discuss the applications of C. elegans to nanomaterial safety and efficacy evaluations from one health perspective. We also highlight the directions for developing appropriate techniques to safely adopt magnetic and organic nanoparticles, and carbon nanosystems. A description was given of the specifics of targeting and treatment, especially for health purposes. Finally, we discuss C. elegans potential for studying the impacts caused by nanopesticides and nanoplastics as emerging contaminants, pointing out gaps in environmental studies related to toxicity, analytical methods, and future directions.

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Nanocarriers can deliver drugs to specific organs or cells, potentially bridging the gap between a drug's function and its interaction with biological systems such as human physiology. The untapped potential of nanotechnology stems from its ability to manipulate materials, allowing control over physical and chemical properties and overcoming drug-related problems, e.g., poor solubility or poor bioavailability. For example, most protein drugs are administered parenterally, each with challenges and peculiarities. Some problems faced by bioengineered macromolecule drugs leading to poor bioavailability are short biological half-life, large size and high molecular weight, low permeability through biological membranes, and structural instability. Nanotechnology emerges as a promising strategy to overcome these problems. Nevertheless, the delivery system should be carefully chosen considering loading efficiency, physicochemical properties, production conditions, toxicity, and regulations. Moving from the bench to the bedside is still one of the major bottlenecks in nanomedicine, and toxicological issues are the greatest challenges to overcome. This review provides an overview of biotech drug delivery approaches, associated nanotechnology novelty, toxicological issues, and regulations.

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Rifampicin has broad-spectrum antimicrobial activity, but it can cause nephrotoxic and hepatotoxic damage because high doses are required. Nanosystems emerge as a perspective to improve the transport systems of this drug. In this work, iron oxide nanoparticles were synthesised, functionalized with lauric acid, and rifampicin was incorporated into the nanosystem. The samples were characterized by spectroscopic techniques: electronics in the visible ultraviolet region (UV-vis), vibrational absorption in the infrared region (IR), X-ray diffractometry (XRD), and dynamic light scattering (DSL). The toxicity of the nanocompounds and the antimicrobial activity against Staphylococcus aureus ATCC 25923 were studied by the Artemia salina lethality and disc diffusion techniques, respectively. As a result, IR analysis showed characteristic vibrations of laurate and rifampicin on the surface of the nanosystem. The presence of magnetic iron oxide was confirmed by XRD and the mean diameter of the crystallites was 8.37 nm. The hydrodynamic diameter of rifampicin associated with the nanosystem was 402 nm and that of the nanosystem without rifampicin was 57 nm. The compounds did not show toxicity to Artemia salina and the in vitro antimicrobial activity against Staphylococcus aureus was slightly decreased when rifampicin was associated with the nanosystem. In general terms, the results showed that iron oxide nanoparticles showed no toxicity and reduced the toxicity of rifampicin by 41.54% when carried compared to free rifampicin. Therefore, magnetic iron oxide nanoparticles may have the potential to act as a platform for associated drugs.

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In this work, the toxicity and biodistribution of graphene oxide (GO) and oxidized multi-walled carbon nanotubes (MWCNT) were investigated in Caenorhabditis elegans. Bovine serum albumin (BSA) was selected as a model protein to evaluate the influence of protein corona formation on materials physicochemical properties, colloidal stability, and toxicity. Biological assays were performed to assess the effects of bare and albumin corona coated materials on survival, oxidative stress, intestinal barrier permeability, growth, reproduction, and fertility. Critical alterations in topography, surface roughness and chemistry of GO and MWCNT were observed due to albumin corona formation. These modifications were associated with changes in colloidal stability of materials and prevention of their aggregation and sedimentation in nematode testing medium. Both GO and MWCNT caused damage to nematode survival, growth, reproduction, and fertility, as well as enhanced oxidative stress and permeability of the intestinal barrier. But GO was more toxic than MWCNT to C. elegans, especially at long-term assays. Albumin corona mitigated 100% of acute and chronic effects of MWCNT. In contrast, the negative effects of GO were not completely mitigated; GO inhibited 16.2% of nematode growth, 86.5% of reproduction, and 32.0% of fertility at the highest concentration evaluated (10 mg L-1), while corona coated GO mitigated 50% and 100% of fertility and growth, respectively. Confocal Raman spectroscopy imaging was crucial to point out that bare and albumin corona coated GO and MWCNT crossed the C. elegans intestinal barrier reaching its reproductive organs. However, BSA corona protected the nematodes targeted organs from negative effects from MWCNT and blocked its translocation to other tissues, while coated GO was translocated inside the nematode affecting the functionality of crucial organs. In addition, coated MWCNT was excreted after 2 h of food resumption, whereas coated GO still accumulated in the nematode intestine. Our results demonstrate that the materials different translocation and excretion patterns in C. elegans had a relation to the impaired physiological functions of primary and secondary organs. This work is a contribution towards a better understanding of the impacts of protein corona on the toxicity of graphene oxide and carbon nanotubes; essential information for biological applications and nanosafety.

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Green nanoparticles (GNPs), mainly green silver nanoparticles (Ag NPs), have been recommended as sustainable and eco-friendly technologies to control vectors and intermediate hosts. The aim of the current study is to carry out a historical and systematic literature review about the use of green plant-based Ag NPs (GP-Ag NPs) to control medically important mosquito, tick and gastropods. Data about the number of studies published per year, geographical distribution of studies (mailing address of the corresponding author), synthesis type (plant species, plant structure and extract types), physicochemical properties of GP-Ag NPs, experimental designs, developmental stages and the toxic effects on mosquitoes, ticks and gastropods were summarized and discussed. Revised data showed that GP-Ag NPs synthesis and toxicity in mosquitoes, ticks and snails depend on plant species, plant part, extract types, exposure condition and on the analyzed species. GP-Ag NPs induced mortality, tissue damage, biochemical and behavioral changes in mosquitoes and reduced their fecundity, oviposition, egg hatching and longevity. Ticks exposed to GP-Ag NPs presented increased mortality and reduced oviposition, while on snails, studies demonstrated mortality, oxidative stress, and DNA damage. Immune responses were also observed in snails after their exposure to GP-Ag NPs. GP-Ag NPs reduced the reproduction and population of several vectors and intermediate hosts. This finding confirms their potential to be used in gastropod control programs. Future studies about current gaps in knowledge are recommended.

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The production and use of titanium dioxide (TiO2) nanoparticles are increasing worldwide. The release of this substance into the environment can induce toxic effects in aquatic invertebrates and vertebrates, although the exact nature of its impacts on Neotropical amphibians is still poorly understood. In this context, the present study evaluated the toxicity of TiO2 nanoparticles and their counterpart-dissolved titanium dioxide (TiO2)-in the tadpoles of Dendropsophus minutus. The biometric parameters, DNA damage, and behavioral changes were verified in tadpoles exposed to three different concentrations (0.1 mg·L-1, 1.0 mg·L-1, and 10 mg·L-1) of TiO2 nanoparticles and dissolved TiO2 for 7 days. We verified significant DNA damage in the D. minutus tadpoles exposed to both forms of Ti, in comparison with the control group. We also identified a reduction in total size, body length, and width, and the height of the musculature of the tail of the tadpoles exposed to all concentrations of both substances in comparison with the control. In the behavioral test, the tadpoles exposed to nanoparticles and dissolved TiO2 presented reduced mobility and a tendency to be less aggregated than normal. Here, the simultaneous use of multiple biomarkers was fundamental for the reliable assessment of the adverse effects of nanomaterials on anuran amphibians and the establishment of a systematic approach to the biomonitoring of aquatic ecosystems. The present study expands our understanding of the genotoxic, morphological, and behavioral effects of TiO2 nanoparticles and dissolved TiO2 on anuran amphibians, and contributes to the establishment of further research for the more systematic assessment of the environmental risk of nanomaterials.

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Cellulose nanofibers (CNFs) are natural polymers with physical-chemical properties that make them very attractive for modulating stem cell differentiation, a crucial step in tissue engineering and regenerative medicine. Although cellulose is cytocompatible, when materials are in nanoscale, they become more reactive, needing to evaluate its potential toxic effect to ensure safe application. This study aimed to investigate the cytocompatibility of cotton CNF and its differentiation capacity induction on stem cells from human exfoliated deciduous teeth. First, the cotton CNF was characterized. Then, the cytocompatibility and the osteogenic differentiation induced by cotton CNF were examined. The results revealed that cotton CNFs have about 6-18 nm diameters, and the zeta potential was -10 mV. Despite gene expression alteration, the cotton CNF shows good cytocompatibility. The cotton CNF induced an increase in phosphatase alkaline activity and extracellular matrix mineralization. The results indicate that cotton CNF has good cytocompatibility and can promote cell differentiation without using chemical inducers, showing great potential as a new differentiation inductor for tissue engineering and regenerative medicine applications.

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The titanium dioxide nanoparticles (NPs) have been applied to biomedical, pharmaceutical, and food additive fields. However, the effect on health and the environment are conflicting; thus, it has been reviewing several times. In this context, establishing standard robust protocols for detecting cytotoxicity and genotoxicity of nanomaterials became essential for nanotechnology development. The cell type and the intrinsic characteristics of titanium dioxide NPs can influence nanotoxicity. In this work, the cyto- and genotoxicity effects of standard reference material titanium dioxide NPs in primary bovine fibroblasts and immortalized Chinese hamster ovary epithelial (CHO) cells were determined and compared for the first time. Titanium dioxide NPs exposure revealed no cytotoxicity for primary bovine fibroblasts, while only higher concentrations tested (10 µg/ml) induce genotoxic effects in this cell model. In contrast, the lower concentrations of the titanium dioxide NPs cause the cyto- and genotoxic effects in CHO cells. Therefore, our finding indicates that the CHO line was more sensitive toward the effects of titanium dioxide NPs than the primary bovine fibroblast, which should be valuable for their environmental risk assessment.

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Graphene oxide (GO) is a promising and strategic carbon-based nanomaterial for innovative and disruptive technologies. It is therefore essential to address its environmental health and safety aspects. In this work, we evaluated the chemical degradation of graphene oxide by sodium hypochlorite (NaClO, bleach water) and its consequences over toxicity, on the nematode Caenorhabditis elegans. The morphological, chemical, and structural properties of GO and its degraded product, termed NaClO-GO, were characterized, exploring an integrated approach. After the chemical degradation of GO at room temperature, its flake size was reduced from 156 to 29 nm, while NaClO-GO showed changes in UV-vis absorption, and an increase in the amount of oxygenated surface groups, which dramatically improved its colloidal stability in moderately hard reconstituted water (EPA medium). Acute and chronic exposure endpoints (survival, growth, fertility, and reproduction) were monitored to evaluate material toxicities. NaClO-GO presented lower toxicity at all endpoints. For example, an increase of over 100% in nematode survival was verified for the degraded material when compared to GO at 10 mg L-1. Additionally, enhanced dark-field hyperspectral microscopy confirmed the oral uptake of both materials by C. elegans. Finally, this work represents a new contribution toward a better understanding of the links between the transformation of graphene-based materials and nanotoxicity effects (mitigation), which is mandatory for the safety improvements that are required to maximize nanotechnological benefits to society.

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The use of silver nanoparticles (AgNPs) in commercial products has increased due to their antibacterial properties and their impacts on the environment must be investigated. This scenario has motivated the conduction of this study, which relates different factors that affect the toxicity of AgNPs to the aquatic plant Lemna minor such as size, accumulation, concentration, and dissolution of AgNPs. To this end, synthesized AgNPs measuring 30, 85, and 110 nm were added into the culture medium to observe toxicity for 30 days. The mapping by SEM showed that the smallest AgNPs can translocate from roots to leaves due to its mobility and internalization. As predicted by the Ostwald equation, the solubility for 30-nm AgNPs increased almost 3 times at the end of 30 days, while for 85 and 110 nm size nanoparticles, after 7 days, the solubility decreased due to "Ostwald ripening" process. Plant mortality was assessed and, after 1 month, the size of 30 nm was the most toxic with negative growth in all studied concentrations, with 60% mortality in the worst case. The concentration of 50 µg mL-1 was toxic in all sizes with negative growth in the period. Therefore, the investigation of AgNPs' toxicity needs to consider a different factor to better understand their effects on aquatic plants and the environment.

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The toxicity of zinc oxide (ZnO NPs) and polystyrene nanoplastics (PS NaPs) has been tested in different animal models; however, knowledge about their impact on mice remains incipient. The aim of the current study is to evaluate the effects of these nanomaterials on Swiss mice after their individual exposure to a binary combination of them. The goal was to investigate whether short exposure (three days) to an environmentally relevant dose (14.6 ng/kg, i.p.) of these pollutants would have neurotoxic, biochemical and genotoxic effects on the modelss. Data in the current study have shown that the individual exposure of these animals has led to cognitive impairment based on the object recognition test, although the exposure experiment did not cause locomotor and anxiogenic or anxiolitic-like behavioral changes in them. This outcome was associated with increased nitric oxide levels, thiobarbituric acid reactive species, reduction in acetylcholinesterase activity and with the accumulation of nanomaterials in their brains. Results recorded for the assessed parameters did not differ between the control group and the groups exposed to the binary combination of pollutants. However, both the individual and the combined exposures caused erythrocyte DNA damages associated with hypercholesterolemic and hypertriglyceridemic conditions due to the presence of nanomaterials. Based on the results, the toxicological potential of ZnO NPs and PS NaPs in the models was confirmed and it encouraged further in-depth investigations about factors explaining the lack of additive or synergistic effect caused by the combined exposure to the assessed pollutants.

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In recent years, advanced nanohybrid materials processed as pharmaceuticals have proved to be very advantageous. Triptans, such as the commercially available intranasal sumatriptan (SMT), are drugs employed in the treatment of painful migraine symptoms. However, SMT effectiveness by the intranasal route is limited by its high hydrophilicity and poor mucoadhesion. Therefore, we designed hybrid nanoemulsions (NE) composed of copaiba oil as the organic component plus biopolymers (xanthan, pectin, alginate) solubilized in the continuous aqueous phase, aiming at the intranasal release of SMT (2% w/v). Firstly, drug-biopolymer complexes were optimized in order to decrease the hydrophilicity of SMT. The resultant complexes were further encapsulated in copaiba oil-based nanoparticles, forming NE formulations. Characterization by FTIR-ATR, DSC, and TEM techniques exposed details of the molecular arrangement of the hybrid systems. Long-term stability of the hybrid NE at 25°C was confirmed over a year, regarding size (~ 120 nm), polydispersity (~ 0.2), zeta potential (~ -25 mV), and nanoparticle concentration (~ 2.1014 particles/mL). SMT encapsulation efficiency in the formulations ranged between 41-69%, extending the in vitro release time of SMT from 5 h (free drug) to more than 24 h. The alginate-based NE was selected as the most desirable system and its in vivo nanotoxicity was evaluated in a zebrafish model. Hybrid NE treatment did not affect spontaneous movement or induce morphological changes in zebrafish larvae, and there was no evidence of mortality or cardiotoxicity after 48 h of treatment. With these results, we propose alginate-based nanoemulsions as a potential treatment for migraine pain.