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Emerging nanopesticides are gradually gaining widespread application in agriculture due to their excellent properties, but their potential risks to pollinating insects are not fully understood. In this study, lambda-cyhalothrin nanocapsules (LC-NCs) were constructed by electrostatic self-assembly method with iron mineralization optimization, and their effects on bee gut microbial communities and host immune-related factors were investigated. Microbiome sequencing revealed that LC-NCs increase the diversity of gut microbial communities and reduce the complexity of network features, disrupting the overall structure of the microbial communities. In addition, LC-NCs also had systemic effects on the immune response of bees, including increased activity of SOD and CAT enzymes and expression of their genes, as well as downregulation of Defensin1. Furthermore, we noticed that the immune system of the host was activated simultaneously with a rise in the abundance of beneficial bacteria in the gut. Our research emphasizes the importance of both the host and gut microbiota of holobiont in revealing the potential risks of LC-NCs to environmental indicators of honey bees, and provides references for exploring the interactions between host-microbiota systems under exogenous stress. At the same time, we hope that more research can focus on the potential impacts of nanopesticides on the ecological environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diazepam (DZP) is a sedative medication prescribed to treat anxiety and as a sleep inducer, although its residual effects are unfavorable to patients. Nanotechnology represents a tool to improve the pharmacological characteristics of drugs, reducing their side effects. This study aimed to develop and characterize DZP nanocapsules and to evaluate their toxicity in alternative models and the hypnotic-sedative effect in mice. Nanocapsules were prepared by the nanoprecipitation method and properly characterized. Long-term and accelerated stability studies were performed. The in vitro release profile was determined by diffusion in Franz cells. The safety of the formulation was evaluated in the Caenorhabditis elegans (C. elegans) and the oral acute toxicity in mice. Pharmacological evaluation was performed using thiopental-induced sleeping time. DZP was successfully incorporated into Poly-(ɛ-caprolactone) (PCL) nanocapsules, with high entrapment efficiency. The nanocapsule did not affect the development or survival of C. elegans, different from the free drug, which affected the nematode development at the higher tested dose. No signs of toxicity, nor body mass or feed consumption changes were observed during the 14 days evaluated. Finally, this innovative formulation carrying DZP can produce a hypnotic-effect at a reduced dose compared to the free drug, with no toxicity in alternative models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nanotechnology involves the utilization of nanomaterials, including polymeric nanocapsules (NCs) that are drug carriers. For modify drug release and stability, nanoformulations can feature different types of polymers as surface coatings: Polysorbate 80 (P80), Polyethylene glycol (PEG), Chitosan (CS) and Eudragit (EUD). Although nanoencapsulation aims to reduce side effects, these polymers can interact with living organisms, inducing events in the antioxidant system. Thus far, little has been described about the impacts of chronic exposure, with Drosophila melanogaster being an in vivo model for characterizing the toxicology of these polymers. This study analyzes the effects of chronic exposure to polymeric NCs with different coatings. Flies were exposed to 10, 50, 100, and 500 μL of NCP80, NCPEG, NCCS, or EUD. The survival rate, locomotor changes, oxidative stress markers, cell viability, and Nrf2 expression were evaluated. Between the coatings, NCPEG had minimal effects, as only 500 μL affected the levels of reactive species (RS) and the enzymatic activities of catalase (CAT) and glutathione S-transferase (GST) without reducing Nrf2 expression. However, NCEUD significantly impacted the total flies killed, RS, CAT, and Superoxide dismutase from 100 μL. In part, the toxicity mechanisms of these coatings can be explained by the imbalance of the antioxidant system. This research provided initial evidence on the chronic toxicology of these nanomaterials in D. melanogaster to clarify the nanosafety profile of these polymers in future nanoformulations. Further investigations are essential to characterize possible biochemical pathways involved in the toxicity of these polymeric coatings., Competing Interests: Declaration of competing interest The authors declare that this research was conducted in the absence of any financial or commercial relationships, therefore there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

We investigated a possible toxic effect induced by chronic exposure to free curcumin and curcumin-loaded nanocapsules in Drosophila melanogaster, enabling safe applications. Flies of both sexes were divided into groups: control group; free curcumin at concentrations of 10, 30, 100, 300, 900, and 3000 μM; curcumin-loaded nanocapsules at concentrations of 10, 30, 100, and 300 μM. Initially, the diet consumption test was evaluated in flies exposed to different concentrations. During the 10-day treatment, the flies were evaluated for percentage survival. After the treatment, behaviors (geotaxis negative and open field), acetylcholinesterase activity (AChE), and oxidative stress parameters (reactive species (RS) and thiobarbituric acid reactive substances (TBARS) levels, Glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) enzymes activity, erythroid-derived nuclear factor 2 (Nrf2) immunoreactivity, and cellular metabolic capacity, were assessed. No significant difference in diet consumption, indicating that the flies equally consumed the different concentrations of free curcumin and the curcumin-loaded nanocapsules. Was observed that free curcumin and curcumin-loaded nanocapsules increased survival, locomotor and exploratory performance, decreased AChE activity, RS and TBARS levels, increased GST, SOD and CAT activity, Nrf2 and viable cells compared to the control. The chronic treatment did not cause toxicity, suggesting that nanoencapsulation of curcumin could be explored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Curcumin is an active polyphenol substance found in the highest concentrations in the roots of Curcuma longa. Its health benefits have led to recent increases in the consumption of curcumin. It has anti-inflammatory and antioxidant activities and is a potent neuroprotective against diseases of the brain. Nevertheless, its low bioavailability and its relative difficulty crossing the blood-brain barrier limit curcumin's use for these purposes. Curcumin-loaded nanoparticles may be an effective treatment for several diseases although there is a paucity of studies reporting its safety in the central nervous system (CNS). Therefore, this study aimed to identify non-neurotoxic concentrations of free curcumin and two nanoformulations of curcumin. Cell lines BV-2 and SH-SY5Y, both originating from the CNS, were evaluated after 24, 48, and 72 h of treatment with free curcumin and nanocapsules We measured viability, proliferation, and dsDNA levels. We measured levels of reactive oxygen species and nitric oxide as proxies for oxidative stress in culture supernatants. We found that free curcumin was toxic at 10 and 20 µM, principally at 72 h. Nanoformulations were more neurotoxic than the free form. Safe concentrations of free curcumin are between 1-5 µM, and these concentrations were lower for nanoformulations. We determined the ideal concentrations of free curcumin and nanocapsules serving as a basis for studies of injuries that affect the CNS.

Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Recently, size-controlled pesticide microcapsule (MC) delivery systems have played an important role in precision farming development; however, the potential environmental hazards of MCs with different particle sizes have not been fully characterized. In this study, we prepared a series of lambda-cyhalothrin (LC)-MCs with nano and micron-scale capsule sizes (average diameters of 209.4 nm, MC-N; 2.41 µm, MC-S; 4.87 µm, MC-M; and 12.41 µm, MC-L). The assessment results showed that the release and sedimentation behavior of LC-MCs in water and toxicity to zebrafish at three life stages were all particle size-dependent. As the diameter distribution of approximately 100 nm extended to the micron scale (~27 µm), the capsules released more slowly and sunk more quickly in water. In addition, micron-sized LC-MC exposure resulted in significantly less fish mortality and malformations of larvae and embryos compared with nanosized LC-MC exposure. The highest accumulation of MC-N in the gill and the severest toxicity to larvae suggested that the smaller size and stronger permeability of nanocapsules would pose unpredictable consequences for nontargeted organisms. The obvious toxicological differences of LC-MCs toward aquatic organisms implies that regulating MC production in an appropriate size range is an important prerequisite for achieving efficient but safe pesticide applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nanocapsules are a promising controlled release formulation for foliar pest control. However, the complicated process and high cost limit widespread use in agriculture, so a simpler and more convenient preparation system is urgently needed. Meanwhile, under complex field conditions, the advantageous mechanism of the nanosize effect and sustained release have no quantitative and detailed study. In this study, a reactive emulsifier (OP-10) is used to participate in the interfacial polymerization of the nanoemulsion, and polymer nanocapsules loaded with lambda-cyhalothrin (NCS@LC) are quickly and easily prepared to study the efficacy and synergistic mechanism of foliar pest control. As a result, the nanocapsule is about 150 nm with a stable core-shell structure. The nanoscale state increases the distribution and adhesion of the particles on the leaf surface, which increases the contact efficiency of pesticides under the different physiological stages and behavioral activities of the target organism. The shell structure provides sustained release characteristics and increases the UV resistance by about 2.5 times for pesticides. Compared with microcapsules loaded with lambda-cyhalothrin (CS@LC), NCS@LC not only shows rapid and synergistic insecticidal efficacy but also provides sustained insecticidal efficacy. The mortality of NCS is 3.4 times that of the nanosized emulsion in water (NEW) at the lowest concentration (0.5 mg L -1 ), and the control efficacy remained 77.3% after 7 days. Compared with NEW, NCS@LC provides excellent field efficacy, while LC 50 for zebrafish is only 0.68 times without increasing the aquatic toxicity risk.

Herein, we demonstrate a novel UV-induced decomposable nanocapsule of natural polysaccharide (HA-azo/PDADMAC). The nanocapsules are fabricated based on layer-by-layer co-assembly of anionic azobenzene functionalized hyaluronic acid (HA-azo) and cationic poly diallyl dimethylammonium chloride (PDADMAC). When the nanocapsules are exposed to 365 nm light, ultraviolet photons can trigger the photo-isomerization of azobenzene groups in the framework. The nanocapsules could decompose from large-sized nanocapsules to small fragments. Due to their optimized original size (~180 nm), the nanocapsules can effectively avoid biological barriers, provide a long blood circulation and achieve high tumor accumulation. It can fast eliminate nanocapsules from tumor and release the loaded drugs for chemotherapy after UV-induced dissociation. Besides, HA is an endogenous polysaccharide that shows intrinsic targetability to CD44 receptors on surface of cancer cells. The intracellular experiment shows that the HA-azo/PDADMAC nanocapsules with CD44 targeting ability and UV-controlled intracellular drug release are promising for cancer chemotherapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In this study, a biocompatible folate-decorated reductive-responsive carboxymethylcellulose-based nanocapsules (FA-RCNCs) were designed and prepared via sonochemical method for targeted delivery and controlled release of hydrophobic drugs. The shell of FA-RCNCs was cross-linked by disulfide bonds formed from hydrosulfuryl groups on the thiolated carboxymethylcellulose (TCMC) and encapsulated hydrophobic drug dispersed in the oil phase into nanocapsules. Moreover, the size and morphology of drug loaded FA-RCNCs were characterized by DLS, SEM and CLSM which indicated that the synthesized nanocapsules have suitable size range and excellent stability for circulating in the bloodstream. The drug release rate of FA-RCNCs could be controlled by adjusting their sizes and shell thickness, which could be dominated by the concentration of TCMC and sonochemical conditions. Furthermore, the obtained FA-RCNCs could be ingested into Hela cells via folate-receptor (FR)-mediated endocytosis and quickly release drugs under reductive environment, which demonstrated that FA-RCNCs could become potential hydrophobic drugs carries for cancer therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Polymer nanocapsules, with a hollow structure, are increasingly finding widespread use as drug delivery carriers; however, quantitatively evaluating the bio-nano interactions of nanocapsules remains challenging. Herein, poly(ethylene glycol) (PEG)-based metal-phenolic network (MPN) nanocapsules of three sizes (50, 100, and 150 nm) are engineered via supramolecular template-assisted assembly and the effect of the nanocapsule size on bio-nano interactions is investigated using in vitro cell experiments, ex vivo whole blood assays, and in vivo rat models. To track the nanocapsules by mass cytometry, a preformed gold nanoparticle (14 nm) is encapsulated into each PEG-MPN nanocapsule. The results reveal that decreasing the size of the PEG-MPN nanocapsules from 150 to 50 nm leads to reduced association (up to 70%) with phagocytic blood cells in human blood and prolongs in vivo systemic exposure in rat models. The findings provide insights into MPN-based nanocapsules and represent a platform for studying bio-nano interactions.

Mucoadhesive polymeric nanocapsules have attracted interest of researchers from different fields from natural sciences because of their ability to interact with the mucosa and increase drug permeation. Anesthesia by immersion causes absorption through the skin and gills of fish, so it is important to evaluate the exposure of these organs to drug nanosystems. Benzocaine (BENZ) is one of the most popular anesthetic agents used in fish anesthesia, but it has drawbacks because of its low bioavailability, resulting in weak absorption after immersion. Here we describe method developed for preparing and characterizing chitosan-coated PLGA mucoadhesive nanoparticles containing BENZ (NPMAs) for zebrafish immersion anesthesia. We determined the lowest effective concentration, characterized the interaction of the mucoadhesive system with fish, measured the anesthetic efficacy, and evaluated possible toxic effects in embryos and adults exposed to the nanoformulations. This study opens perspectives for using nanoformulations prepared with BENZ in aquaculture, allowing reduction of dosage as well as promoting more effective anesthesia and improved interaction with the mucoadhesive system of fish., Competing Interests: The authors have read the journal’s policy and have the following potential competing interests: authors LFF and GBdM are members of the PLOS ONE Editorial Board. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Galleria mellonella larvae is an invertebrate that has been extensively used as experimental model in the investigation of microbial virulence and efficacy of antimicrobial agents and can be used to provide faster and cheaper data than traditional test systems. Our objective was to propose the use of G. mellonella larvae as an In Vivo model to evaluate the toxicity of lipid-core nanocapsule (LNC) formulations having different surface coatings. Blank LNC formulations were coated with polysorbate 80 (LNC-1), lecithin and polysorbate 80 (LNC-2), and lecithin, chitosan and polysorbate 80 (LNC-3). Subsequently, the formulations were systemically administered to G. mellonella larvae at doses of 3.75×10 -14 , 3.75×10 -13 , 3.75×10 -12 , 3.75×10 -11 and 3.75×10 -10 mols of LNC per kg of larvae. The results demonstrated that those nanocapsules having neutral (LNC-1), negative (LNC-2) or positive (LNC-3) surface did not show acute toxicity effects in G. mellonella larvae. G. mellonella larvae is a viable and promising alternative for In Vivo nanotoxicological studies. We conclude that G. mellonella larvae can be used as an alternative model for the screening of the toxicity of polymeric nanocapsules functionalized with (i) polysorbate 80, (ii) lecithin and polysorbate 80, and (iii) lecithin, chitosan and polysorbate 80. Future studies can be now developed in order to evaluate their toxicity when loaded or functionalized with drugs.

Minimization of drug side effects is a hallmark of advanced targeted therapy. Herein we describe the synthesis of polysaccharide-based nanocapsules prepared from furcellaran and chitosan via layer-by-layer deposition using electrostatic interaction. Using doxorubicin as a model drug, prepared nanocapsules showed excellent drug loading properties and release influence by pH and stability. Targeted delivery of doxorubicin was achieved by nanocapsule surface modification using homing peptide (seq SMSIARLC). The synthesized nanocapsules possess excellent compatibility to eukaryotic organisms. In the case of nonmalignant cells (PNT1A and HEK-293), toxicity tests revealed the absences of DNA fragmentation, apoptosis, necrosis, and also disruption of erythrocyte membranes. In contrast, results from treatment of malignant cell lines (MDA-MB-231 and PC3) indicate good anticancer effects of synthesized bionanomaterial. Internalization studies revealed the nanocapsule's ability to enter the malignant cell lines by endocytosis and triggering the apoptosis. The occurrence of apoptosis is mostly connected to the presence of ROS and inability of DNA damage reparation. Additionally, the obtained results strongly indicate that peptide modification increases the speed of nanocapsule internalization into malignant cell lines while simultaneously nonmalignant cell lines are untouched by nanocapsules highlighting the strong selectivity of the peptide.

The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.

Nanoencapsulation is a rapidly expanding technology to enclose cargo into inert material at the nanoscale size, which protects cargo from degradation, improves bioavailability and allows for controlled release. Encapsulation of drugs into functional nanocarriers enhances their specificity, targeting ability, efficiency, and effectiveness. Functionality may come from cell targeting biomolecules that direct nanocarriers to a specific cell or tissue. Delivery is usually mediated by diffusion and erosion mechanisms, but in some cases, this is not sufficient to reach the expected therapeutic effects. This work reports on the development of a new photoresponsive polymeric nanocarrier (PNc)-based nanobioconjugate (NBc) for specific photo-delivery of cargo into target cells. We readily synthesized the PNcs by modification of chitosan with ultraviolet (UV)-photosensitive azobenzene molecules, with Nile red and dofetilide as cargo models to prove the encapsulation/release concept. The PNcs were further functionalized with the cardiac targeting transmembrane peptide and efficiently internalized into cardiomyocytes, as a cell line model. Intracellular cargo-release was dramatically accelerated upon a very short UV-light irradiation time. Delivering cargo in a time-space controlled fashion by means of NBcs is a promising strategy to increase the intracellular cargo concentration, to decrease dose and cargo side effects, thereby improving the effectiveness of a therapeutic regime.

Background: Lipid nanocapsules (LNCs) are promising vehicles for drug delivery. However, since not much was known about cellular toxicity of these nanoparticles in themselves, we have here investigated the mechanisms involved in LNC-induced intoxication of the three breast cancer cell lines MCF-7, MDA-MD-231 and MDA-MB-468. The LNCs used were made of Labrafac™ Lipophile WL1349, Lipoid ® S75 and Solutol ® HS15., Results: High resolution SIM microscopy showed that the DiD-labeled LNCs ended up in lysosomes close to the membrane. Empty LNCs, i.e. without encapsulated drug, induced not only increased lysosomal pH, but also acidification of the cytosol and a rapid inhibition of protein synthesis. The cytotoxicity of the LNCs were measured for up to 72 h of incubation using the MTT assay and ATP measurements in all three cell lines, and revealed that MDA-MB-468 was the most sensitive cell line and MCF-7 the least sensitive cell line to these LNCs. The LNCs induced generation of reactive free oxygen species and lipid peroxidation. Experiments with knock-down of kinases in the near-haploid cell line HAP1 indicated that the kinase HRI is essential for the observed phosphorylation of eIF2α. Nrf2 and ATF4 seem to play a protective role against the LNCs in MDA-MB-231 cells, as knock-down of these factors sensitizes the cells to the LNCs. This is in contrast to MCF-7 cells where the knock-down of these factors had a minor effect on the toxicity of the LNCs. Inhibitors of ferroptosis provided a large protection against LNC toxicity in MDA-MB-231 cells, but not in MCF-7 cells., Conclusions: High doses of LNCs showed a different degree of toxicity on the three cell lines studied, i.e. MCF-7, MDA-MD-231 and MDA-MB-468 and affected signaling factors and the cell fate differently in these cell lines.

Background: The functionalization of a nanoparticle surface with PEG (polyethylene glycol) is an approach most often used for extending nanomaterial circulation time, enhancing its delivery and retention in the target tissues, and decreasing systemic toxicity of nanocarriers and their cargos. However, because PEGylated nanomedicines were reported to induce immune response including production of anti-PEG antibodies, activation of the complement system as well as hypersensitivity reactions, hydrophilic polymers other than PEG are gaining interest as its replacement in nanomaterial functionalization. Here, we present the results of in vivo evaluation of polyelectrolyte nanocapsules with biodegradable, polyelectrolyte multilayer shells consisting of poly-l-lysine (PLL) and poly-l-glutamic (PGA) acid as a potential drug delivery system. We compared the effects of nanocapsules functionalized with two different "stealth" polymers as the external layer of tested nanocapsules was composed of PGA (PGA-terminated nanocapsules, NC-PGA) or the copolymer of poly-l-lysine and polyethylene glycol (PEG-terminated nanocapsules, NC-PEG)., Methods: Nanocapsules pharmacokinetics, biodistribution and routes of eliminations were analysed postmortem by fluorescence intensity measurement. Toxicity of intravenously injected nanocapsules was evaluated with analyses of blood morphology and biochemistry and by histological tissue analysis. DNA integrity was determined by comet assay, cytokine profiling was performed using flow cytometer and detection of antibodies specific to PEG was performed by ELISA assay., Results: We found that NC-PGA and NC-PEG had similar pharmacokinetic and biodistribution profiles and both were eliminated by hepatobiliary and renal clearance. Biochemical and histopathological evaluation of long-term toxicity performed after a single as well as repeated intravenous injections of nanomaterials demonstrated that neither NC-PGA nor NC-PEG had any acute or chronic hemato-, hepato- or nephrotoxic effects. In contrast to NC-PGA, repeated administration of NC-PEG resulted in prolonged increased serum levels of a number of cytokines., Conclusion: Our results indicate that NC-PEG may cause undesirable activation of the immune system. Therefore, PGA compares favorably with PEG in equipping nanomaterials with stealth properties. Our research points to the importance of a thorough assessment of the potential influence of nanomaterials on the immune system., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Karabasz et al.)

Management of infected wounds is one of the most costly procedures in the health care sector. Burn wounds are of significant importance due to the high infection risk that can possibly lead to severe consequences such as sepsis. Because antibiotic wound treatments have caused increasing antibiotic resistance in bacteria, there is currently a strong need for alternative strategies. Therefore, we developed new antimicrobial wound dressings consisting of pH-responsive human serum albumin/silk fibroin nanocapsules immobilized onto cotton/polyethylene terephthalate (PET) blends loaded with eugenol, which is an antimicrobial phenylpropanoid. Ultrasound-assisted production of eugenol-loaded nanocapsules resulted in particle sizes (hydrodynamic radii) between 319.73 ± 17.50 and 574.00 ± 92.76 nm and zeta potentials ranging from -10.39 ± 1.99 mV to -12.11 ± 0.59 mV. Because recent discoveries have indicated that the sweat glands contribute to wound reepithelialisation, release studies of eugenol were conducted in different artificial sweat formulas that varied in pH. Formulations containing 10% silk fibroin with lower degradation degree exhibited the highest release of 41% at pH 6.0. After immobilization, the functionalized cotton/PET blends were able to inhibit 81% of Staphylococcus aureus and 33% of Escherichia coli growth. Particle uniformity, silk fibroin concentration, and high surface-area-to-volume ratio of the produced nanocapsules were identified as the contributing factors leading to high antimicrobial activities against both strains. Therefore, the production of antimicrobial textiles using nanocapsules loaded with an active natural compound that will not contribute to antibiotic resistance is seen as a potential future alternative to commercially available antiseptic wound dressings.

A supramolecular nanocapsule was constructed by the ternary host-guest complexation of azobenzene (Azo) and methylviologen (MV) to cucurbit[8]uril (CB[8]) and the subsequent self-assembly. The supramolecular nanocapsule with both glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities can mimic the intracellular enzymatic reactive oxygen species (ROS) defense system.

The glycerol monolaurate (GML) is a surfactant used in the food industry and has potent antimicrobial activity against many microorganisms; however, the use of GML is not expanded due its high melting point and poor solubility in water. The aim of the study was to produce, characterize, and evaluate in vitro the cytotoxicity of GML and GML nanocapsules. The GML nanocapsules were produced and characterized by a mean diameter, zeta potential, and polydispersity index. The cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, thiobarbituric acid reactive substances (TBARS), and hemolytic activity. The genotoxicity was verified by comet assay. The physicochemical parameters showed a mean diameter of 192.5 ± 2.8 nm, a polydispersity index of 0.061 ± 0.018, and a zeta potential about - 21.9 ± 1 mV. The viability test demonstrated the protector effect of GML nanocapsule compared with the GML on peripheral blood mononuclear cells (PBMC) and VERO cells (isolated from kidney epithelial cells extracted from an African green monkey). A reduction in lipid peroxidation and lactate dehydrogenase release in GML nanocapsule-exposed cells compared with GML treated cells was observed. The damage on erythrocytes was addressed in treatment with GML, while the treatment with GML nanocapsules did not cause an effect. Moreover, the comet assay showed that the GML-caused genotoxicity and GML nanocapsules do not demonstrate damage. The study showed the reduction of toxicity of GML nanocapsules by many methods used in antimicrobial therapy.

Background: Polydatin (PD) is a compound, originally isolated from the root and rhizome of the Chinese herb Polygonum cuspidatum. To date, various biological properties of this compound, such as analgesic, anti-pyretic or diuretic effects, have been shown. Recently, anti-oxidant and anti-inflammatory properties have been widely postulated, yet PD instability and low bioavailability limit its beneficial actions. Therefore, it has been suggested that an encapsulation process may be a promising strategy for overcoming these limitations and increasing the therapeutic efficacy of PD., Methods: We examined the effects of PD in two forms, including free and in PD-loaded polymeric nanocapsules, on lipopolysaccharide (LPS)-induced changes in hippocampal organotypic cultures., Results: Our results indicated that free and encapsulated PD diminished cell death processes and attenuated the secretion of pro-inflammatory cytokines induced by LPS administration. Additionally, PD in both forms strongly inhibited the production of nitric oxide and down-regulated the level of iNOS enzyme in LPS-stimulated hippocampal cultures., Conclusion: Taken together, our study showed that PD exerts anti-inflammatory and anti-oxidant properties in LPS-treated hippocampal organotypic cultures. Furthermore, we show that the encapsulation procedure preserved the features of the free form of this compound, and therefore, the polymeric nanocapsules containing PD may be used as a novel and promising delivery system in therapeutic strategies., (Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

The experimental design aiming at evaluating the performance of drugs nanoencapsulated involves inclusion of a formulation without drug (unloaded). This formulation has sometimes presented per se effect. In this sense, we sought to evaluate the toxicity of unloaded polymeric nanocapsules (NCs) with different surfaces (cationic and anionic) in male Wistar rats in male Wistar rats. The physicochemical characterization of NCs with different surfaces: polysorbate 80 (P80), polyethylene glycol (PEG), eudragit ®RS 100 (EUD) and chitosan (CS) was performed. Rats were treated with unloaded NCs (P80, PEG, EUD and CS surfaces) daily for 14 days per oral route. 24 h of last treatment, animals were euthanized and organs were removed and weighted. After, biochemical determinations were performed. In general, NCs-surfaces did not cause alterations in body weight, weight of organs and histopathological analysis. PEG-surface NCs did not generate hepatotoxicity. In investigation of lipid profile, the surface with P80 changed TC and HDL-C levels. Besides that, all NCs did not alter oxidative stress markers in organs studied (TBARS and Reactive Species) and CS-surface presented antioxidant activity in kidney. This study demonstrated that NCs-surfaces depending on their physicochemical characteristics had low or no toxicity., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Here we report template-free synthesis of imine-linked calix[4]arene hollow nanocapsules and their utility in the effective delivery of a poorly soluble cancer drug into tumor cells. These stimuli-responsive nanocapsules show high drug loading and release which resulted in a 40-fold higher cytotoxicity for breast cancer cell line over normal cells.

Atrazine (ATZ) is a widely used herbicide that has the potential to contaminate the environment and cause deleterious effects on non-target organisms. Release systems for ATZ have been developed to minimize this contamination, such as nanocapsules prepared with poly (ε-caprolactone) (PCL). The objective of this work was to investigate the effects of nanoencapsulated ATZ compared to ATZ on biomarkers of the freshwater teleost Prochilodus lineatus. The fish were exposed for 24 and 96 h to nanoencapsulated ATZ (nATZ) and atrazine (ATZ) at concentrations of 2 and 20 μg L -1 , just to the PCL nanocapsules without the herbicide (NANO) in the corresponding amounts or only to dechlorinated water (CTR). The results showed that nATZ was less toxic compared to ATZ, as it did not promote an increase in glycemia, alterations in antioxidants, nor in carbonic anhydrase enzyme activity, and no increase in the frequency of micronuclei and other nuclear erythrocyte abnormalities either. However, exposure to nATZ, as well as to ATZ and PCL nanocapsules, resulted in a reduction in hemoglobin content, increase in erythrocyte DNA damage, as well as changes in Ca 2+ -ATPase activity, leading to a decrease in plasma Ca +2 . The Integrated Biomarker Response Index (IBR) depicted that exposure to ATZ promoted changes in a greater number of biomarkers compared to nATZ, indicating that the nanoencapsulation of the herbicide protected the animal from the effects of ATZ., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mancozeb is a fungicide widely used in agriculture, mostly against the pathogen Glomerella cingulata responsible for the rot of ripe grape, but presents high toxicity. Strategies are sought to reduce the toxicity of this fungicide and alternative treatments are welcome. An alternative could be the use of clove oil, which has Eugenol as its major compound, and has antifungal potential against G. cingulata, however, Eugenol is susceptible to degradation processes which may compromise its efficacy. The nanoencapsulation of Mancozeb and Eugenol is a possible strategy to overcome the limitations of toxicity, solubility and instability of these compounds. Therefore, the objective of this study is to develop nanoemulsions containing Mancozeb (0.1 mg/mL) and Eugenol (33 mg/mL), isolated or associated, and evaluate the safety of these formulations through cytotoxicity, genotoxicity and ecotoxicity tests. Nanoemulsions were developed by the spontaneous emulsification method, cytotoxicity and genotoxicity were evaluated in healthy human cells through MTT, Dichlorofluorescein diacetate and Picogreen tests, and ecotoxicity assessment was carried out using the chronic toxicity test in springtails. After preparation, the physicochemical characterization of the nanoemulsions were performed which presented mean particle size between 200 and 300 nm, polydispersity index less than 0.3, negative zeta potential and acid pH. The nanoencapsulation was able to avoid the reduction of the cell viability caused by Mancozeb, while Eugenol was shown to be safe for cell use in both free and nanostructured forms, however the association of the two active compounds showed toxicity in the higher doses of Mancozeb. In the ecotoxicity tests, both free Mancozeb and Eugenol forms presented high toxic potential for soil, whereas the nanoencapsulation of these compounds did not cause a reduction in number of springtails. Therefore, from the tests performed, it was possible to observe that nanoencapsulation of Mancozeb and Eugenol is a safe alternative for the application of these compounds mainly in agriculture., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Zwitterionic cross-linked biodegradable nanocapsules (NCs) were synthesized for cancer imaging. A polylactide (PLA)-based diblock copolymer with two blocks carrying acetylenyl and allyl groups respectively was synthesized by ring-opening polymerization (ROP). Azide-alkyne "click" reaction was conducted to conjugate sulfobetaine (SB) zwitterions and fluorescent dye Cy5.5 onto the acetylenyl-functionalized first block of the diblock copolymer. The resulting copolymer with a hydrophilic SB/Cy5.5-functionalized PLA block and a hydrophobic allyl-functionalized PLA block could stabilize miniemulsions because of its amphiphilic diblock structure. UV-induced thiol-ene "click" reaction between a dithiol cross-linker and the hydrophobic allyl-functionalized block of the copolymer at the peripheral region of nanoscopic oil nanodroplets in the miniemulsion generated cross-linked polymer NCs with zwitterionic outer shells. These NCs showed an average hydrodynamic diameter ( D h ) of 136 nm. They exhibited biodegradability, biocompatibility and high colloidal stability. In vitro study indicated that these NCs could be taken up by MIA PaCa-2 cancer cells. In vivo imaging study showed that, comparing to a small molecule dye, NCs had a longer circulation time, facilitating their accumulation at tumors for cancer imaging. Overall, this work demonstrates the applicability of zwitterionic biodegradable polymer-based materials in cancer diagnosis.

We evaluated the influence of nanoencapsulation of the flavonoid Dihydromyricetin (DMY) in reducing the genotoxicity and cytotoxicity induced by cationic nanocapsules. Assays were conducted in order to evaluate the potential of protein corona formation, cytotoxicity, genotoxicity and the antioxidant capacity. Nanocapsules containing DMY (NC-DMY) and free DMY (DMY-F) did not demonstrate cytotoxicity and genotoxicity. However, Eudragit RS100 ® nanocapsules (NC-E) increased cytotoxicity and DNA damage formation. NC-DMY and NC-E presented high interaction with the DNA in vitro, suggesting DNA sequestration. These results indicate that nanoencapsulated DMY does not induce cytotoxicity or genotoxicity, and demonstrates high antioxidant capacity. This antioxidant capacity is probably associated with DMY, and occurs due to its ability to avoid the formation of free radicals, thus preventing the toxicity caused by the nanostructure with the cationic polymer Eudragit RS100 ® . Therefore, NC-DMY can be considered an important formulation with significant antioxidant potential to be exploited by nanomedicine., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Toxicity of nanomaterials is one of the most important factors limiting their medical application. Evaluation of in vitro nanotoxicity allows for the identification and elimination of most of the toxic materials prior to animal testing. The current knowledge of the possible side effects of biodegradable nanomaterials, such as liposomes and polymeric organic nanoparticles, is limited. Previously, we developed a potential drug delivery system in the form of nanocapsules with polyelectrolyte, biodegradable shells consisting of poly-l-lysine and poly-l-glutamic acid (PGA), formed by the layer-by-layer adsorption technique., Methods: Hemolysis assay, viability tests, flow cytometry analysis of vascular cell adhesion molecule-1 expression on endothelium, analysis of nitric oxide production, measurement of intracellular reactive oxygen species levels, detection of antioxidant enzyme activity, and analysis of DNA damage with comet assay were performed to study the in vitro toxicity of nanocapsules., Results: In this work, we present the results of an in vitro analysis of toxicity of five-layer positively charged poly-l-lysine-terminated nanocapsules (NC5), six-layer negatively charged PGA-terminated nanocapsules (NC6) and five-layer PEGylated nanocapsules (NC5-PEG). PGA and polyethylene glycol (PEG) were used as two different "stealth" polymers. Of all the polyelectrolyte nanocapsules tested for blood compatibility, only cationic NC5 showed acute toxicity toward blood cells, expressed as hemolysis and aggregation. Neither NC6 nor NC5-PEG had proinflammatory activity evaluated through changes in the expression of NF-κB-dependent genes, iNOS and vascular cell adhesion molecule-1, induced oxidative stress, or promoted DNA damage in various cells., Conclusion: Our studies clearly indicate that PGA-coated (negatively charged) and PEGylated polyelectrolyte nanocapsules do not show in vitro toxicity, and their potential as a drug delivery system may be safely studied in vivo., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Chagas disease is a public health problem, affecting about 7 million people worldwide. Benznidazole (BZN) is the main treatment option, but it has limited effectiveness and can cause severe adverse effects. Drug delivery through nanoparticles has attracted the interest of the scientific community aiming to improve therapeutic options. The aim of this study was to evaluate the cytotoxicity of benznidazole-loaded calcium carbonate nanoparticles (BZN@CaCO3) on Trypanosoma cruzi strain Y. It was observed that BZN@CaCO3 was able to reduce the viability of epimastigote, trypomastigote and amastigote forms of T. cruzi with greater potency when compared with BZN. The amount of BZN necessary to obtain the same effect was up to 25 times smaller when loaded with CaCO3 nanoparticles. Also, it was observed that BZN@CaCO3 enhanced the selectivity index. Furthermore, the cell-death mechanism induced by both BZN and BZN@CaCO3 was evaluated, indicating that both substances caused necrosis and changed mitochondrial membrane potential.

Drugs used for the treatment and prevention of malaria have resistance-related problems, making them ineffective for monotherapy. If properly associated, many of these antimalarial drugs may find their way back to the treatment regimen. Among the therapeutic arsenal, quinine (QN) is a second-line treatment for uncomplicated malaria but has side effects that limit its use. Curcumin (CR) is a natural compound with anti-plasmodial activities and low bioavailability. In this context, the aim of this work was to develop and characterize co-encapsulated QN + CR-loaded polysorbate-coated polymeric nanocapsules (NC-QC) to evaluate their activity on Plasmodium falciparum and the safety of the nanoformulations for Caenorhabditis elegans. NC-QC displayed a diameter of approximately 200 nm, a negative zeta potential and a slightly basic pH. The drugs are homogeneously distributed in the NCs in the amorphous form. Co-encapsulated NCs exhibited a significant reduction in P. falciparum parasitemia, better than QN/CR. The worms exposed to NC-QC showed higher survival and longevity and no decrease in their reproductive capacity compared to free and associated drugs. It was possible to prove that the NCs were absorbed orally by the worms using fluorescence microscopy. Co-encapsulation of QN and CR was effective against P. falciparum, minimizing the toxic effects caused by chronic exposure of the free drugs in C. elegans., (Copyright © 2018. Published by Elsevier B.V.)

The safety profile of the ingredients used in topical dosage forms and its evaluation is an issue of utmost importance. A suitable equilibrium between safety and efficacy is crucial before promoting a dermatological product. The aim of this work was to assess the safety and biological effects of starch-based vehicles (St-BV) used in such products. The hazard, exposure and dose-response assessment were used to characterize the risk of each ingredient. The EpiSkin™ assay and human repeat insult patch tests were performed to compare the theoretical safety assessment to in vitro and in vivo data. The efficacy of the St-BV was studied using biophysical measurements in human volunteers during 28 days, showing that all ingredients and their combinations were safe for the consumer. Tissue viability determined using the EpiSkin™ testing reached values between 84.0 ± 5.0% and 98.0 ± 8.6% after application of St-BV, which were considered as non-irritant to the skin. These observations were confirmed by the in vivo studies where the St-BV did not induce any sensitization on the volunteers, being safe for human use. Moreover, St-BV increased skin hydration and microcirculation, emerging as an attractive alternative to chemical raw materials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The improvement of in vitro embryo production by culture media supplementation has been a potential tool to increase blastocyst quality and development. Recently, lipid-core nanocapsules (LNC), which were developed for biomedical applications as a drug-delivery system, have demonstrated beneficial effects on in vitro embryo production studies. LNCs have a core composed of sorbitan monostearate dispersed in capric/caprylic triglyceride. Based on that, we firstly investigated if LNCs supplemented during in vitro oocyte maturation had affinity to the mineral oil placed over the top of the IVM media. Also, the effects of LNC supplementation in different concentrations (0; 0.94; 4.71; 23.56; 117.80 and 589.00μg/mL) during the in vitro maturation protocol were evaluated in oocytes and blastocysts by in vitro tests. LNCs seemed not to migrate to the mineral oil overlay during the in vitro oocyte maturation. Interestingly, LNCs did not show toxic effects in the oocyte in vitro maturation rate, cumulus cells expansion and oocyte viability. The highest LNCs concentration tested (589μg/mL) generated the lowest ROS and GSH levels, and reduced apoptosis rate when compared to the control. Additionally, toxic effects in embryo development and quality were not observed. The LNC supramolecular structure demonstrated to be a promising nanocarrier to deliver molecules in oocytes and embryos, aiming the improvement of the embryo in vitro development., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Multifunctional capsules have great applications in biomedical fields. In this study, novel polysaccharide-based nanocapsules were prepared via a layer-by-layer technique using silica as the templates. The shell was constructed based on the electrostatic interactions between pectin and chitosan. The pectin-chitosan nanocapsules ((Pec/Cs) 3 Pec) could keep good colloidal stability within 96h in PBS solution and 48h in BSA solution. Meanwhile, the nanocapsules exhibited a high drug loading and pH-sensitive release property for doxorubicin hydrochloride. Moreover, (Pec/Cs) 3 Pec nanocapsules had no cytotoxicity to both human hepatocellular carcinoma cells (HepG2 cells) and mouse fibroblast cells (L929 cells). More importantly, (Pec/Cs) 3 Pec nanocapsules could be more easily uptaken by HepG2 cells when compared with L929 cells. In vitro anticancer activity tests indicated the carriers could effectively kill HepG2 cells. Overall, (Pec/Cs) 3 Pec nanocapsules have great potential as a novel anticancer drug carrier as a result of their pH-sensitivity, good colloidal stability and anticancer activity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Silibinin (SB) and pomegranate oil (PO) present therapeutic potential due to antioxidant activity, but the biological performance of both bioactives is limited by their low aqueous solubility. To overcome this issue, the aim of the present investigation was to develop nanocapsule suspensions with PO as oil core for SB encapsulation, as well as assess their toxicity in vitro and radical scavenging activity. The nanocapsule suspensions were prepared by interfacial deposition of preformed polymer method. SB-loaded PO-based nanocapsules (SBNC) showed an average diameter of 157 ± 3 nm, homogenous size distribution, zeta potential of -14.1 ± 1.7 mV, pH of 5.6 ± 0.4 and SB content close to 100%. Similar results were obtained for the unloaded formulation (PONC). The nanocapsules controlled SB release at least 10 times as compared with free SB in methanolic solution. The SBNC scavenging capacity in vitro was statistically higher than free SB (p < 0.05). Cell viability in monocytes and lymphocytes was kept around 100% in the treatments with SBNC and PONC, while the SB and the PO caused a decrease around 30% at 50 μM (SB) and 724 μg/mL (PO). Protein carbonyls and DNA damage were minimized by SB and PO nanoencapsulation. Lipid peroxidation occurred in nanocapsule treatments regardless of the SB presence, which may be attributed to PO acting as substrate in reaction. The free compounds also caused lipid peroxidation. The results show that SBNC and PONC presented adequate physicochemical characteristics and low toxicity against human blood cells. Thereby, this novel nanocarrier may be a promising formulation for therapeutic applications.

Aim: To assess the capacity of a new drug delivery nanocapsule (NC) with a double shell of hyaluronic acid and protamine to overcome biological barriers using the zebrafish model., Materials & Methods: NCs were prepared by the solvent displacement method, tagged with fluorescent makers and physicochemically characterized. Toxicity was evaluated according to the Fish Embryo Acute Toxicity test, and permeability was tested by exposing zebrafish, with and without chorion, to the fluorescent NCs., Results: Toxicity of NCs was very low as compared with that of a control nanoemulsion. Double-shell NCs were able to cross chorion and skin., Conclusion: Beyond the potential value of hyaluronic acid:protamine NCs for overcoming epithelial barriers, this works highlights the utility of zebrafish for fast screening of nanocarriers.

Organoselenium compounds have been targeted to new therapeutic tools development due to their pharmacological actions. However, some toxicity issues and physicochemical limitations delay the clinical application of these compounds. The incorporation of organoselenium molecules into nanostructured systems arises as a promising alternative to overcome such restrictions. The current study proposed the characterization of the polymeric nanocapsules of p,p'-methoxyl-diphenyl diselenide [(OMePhSe) 2 ] as well as the evaluation of the in vivo toxicity and biodistribution profile. The nanocapsules, which were composed by medium-chain triglycerides as the oil core and poly(ε-caprolactone) as the polymeric wall, showed nanometric size (236±4), low polydispersity (<0.2), negative zeta potential (-5.4±0.06), neutral pH values (7.2±0.08) and a high encapsulation efficiency (98%). Besides, the nanoencapsulation process increased the (OMePhSe) 2 stability. The repeated intragastric administration of (OMePhSe) 2 nanoencapsulated (25mg/kg/day during 7days) did not cause any alteration in the oxidative status, hematological parameters, and plasma biochemical markers of cellular damage. Moreover, the (OMePhSe) 2 incorporation into nanocapsules increased the selenium concentrations in the tissues (kidneys, liver and plasma) suggesting an improvement in its oral bioavailability., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Tumor hypoxia greatly suppresses the therapeutic efficacy of photodynamic therapy (PDT), mainly because the generation of toxic reactive oxygen species (ROS) in PDT is highly oxygen-dependent. In contrast to ROS, the generation of oxygen-irrelevant free radicals is oxygen-independent. A new therapeutic strategy based on the light-induced generation of free radicals for cancer therapy is reported. Initiator-loaded gold nanocages (AuNCs) as the free-radical generator were synthesized. Under near-infrared light (NIR) irradiation, the plasmonic heating effect of AuNCs can induce the decomposition of the initiator to generate alkyl radicals (R . ), which can elevate oxidative-stress (OS) and cause DNA damages in cancer cells, and finally lead to apoptotic cell death under different oxygen tensions. As a proof of concept, this research opens up a new field to use various free radicals for cancer therapy., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Lipid nanocapsules (LNCs) offer a promising method for the entrapment and nanovectorisation of lipophilic molecules. This new type of nanocarrier, formulated according to a solvent-free process and using only regulatory-approved components, exhibits many prerequisites for being well tolerated. Although toxicological reference values have already been obtained in mice, interaction of LNCs at the cell level needs to be elucidated. LNCs, measuring from 27.0±0.1nm (25nm LNCs) and 112.1±1.8nm (100nm LNCs) and with a zeta potential between -38.7±1.2mV and +9.18±0.4mV, were obtained by a phase inversion process followed by post-insertion of carboxy- or amino-DSPE-PEG. Trypan blue, MTS and neutral red uptake (NRU) assays were performed to evaluate the cytotoxicity of LNCs on mouse macrophage-like cells RAW264.7 after 24h of exposure. The determination of 50% lethal concentration (LC50) showed a size effect of LNCs on toxicity profiles: LC50 ranged from 1.036mg/L (MTS) and 0.477mg/mL (NRU) for 25nm LNCs, to 4.42mg/mL (MTS) and 2.18mg/mL (NRU) for 100nm LNCs. Surfactant Solutol® HS15 has been shown to be the only constituent to exhibit cytotoxicity; its LC50 reached 0.427mg/mL. Moreover, LNCs were not more toxic than their components in simple mixtures. At sublethal concentration, 100nm LNCs only were able to induce a significant production of nitric oxide (NO) by RAW264.7 cells, as assessed by the Griess reaction. Again, surfactant was the only component responsible for an increased NO release (1.8±0.2-fold). Genotoxicity assays revealed no DNA damage on human lymphocytes in both the in vitro Comet and micronucleus assays using 4-hour and 24-hour treatments, respectively., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study aimed to develop poly(ε-caprolactone) nanocapsules loaded with indole-3-cabinol (I3C) using rose hip oil (RHO) or medium chain triglycerides (MCT) as oil core. In vitro radical scavenging activity (DPPH method), hemolysis, and antitumor effects on breast (MCF-7) and glioma (C6) cells were conducted. Preformulation evaluations revealed that RHO is suitable to prepare the nanocapsules considering the log P determination and dissolution/swelling experiments of polymer films. The nanocapsules were prepared and presented adequate physicochemical characteristics as mean size around 250nm, polydispersity index values <0.2, zeta potential negative values and I3C encapsulation efficiency around 42%, without any influence of the oil core (RHO or MCT) on these parameters. However, the photodegradation study demonstrated that RHO nanocapsules showed less degree of I3C degradation in comparison to MCT nanocapsules. The in vitro release profile showed that both nanocapsule suspensions demonstrated an initial burst effect followed by a prolonged I3C release. In addition, the formulations were considered hemocompatibles at 10μg/mL and showed an enhanced radical scavenging activity in comparison to free I3C. Moreover, nanocapsules prepared with RHO increased about two times the antitumor effect of I3C on MCF-7 and C6 cells without significant reduction of astrocyte cell viability. In conclusion, nanocapsule formulations developed in this study might be considered promising for cancer treatment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Glycerol Monolaurate (GML) is a compound with known antimicrobial potential, however it is not much used due to its low solubility in water and high melting point. The nanoencapsulation of some drugs offers several advantages such as improved stability and solubility in water. The present study aimed to produce, characterize, and evaluate the ecotoxicity of GML nanocapsules. The nanocapsules were produced and presented a mean diameter of 210nm, polydispersity index of 0.044, and zeta potential of -23.4mV. The electron microscopy images showed the nanometric size and spherical shape. The assay in soil showed that GML has a high toxicity while the GML nanocapsules showed decreased toxic effects. Nanostructuration also protected the Rhamdia quelen against the toxic effects of GML. Concluding, the formulation shows positive results and is useful to predict the success of development besides not damaging the soil., (Copyright © 2017. Published by Elsevier Inc.)

Accelerated use of pesticides in cutting edge agriculture prompted us to explore smart nanoformulations to subside the consumption of these perilous chemicals. Polymer nanocapsules carrying a fungicide, hexaconazole were developed through ionotropic gelation method utilizing chitosan and tripolyphosphate (TPP). The nanocapsules were characterized by photon correlation spectroscope (PCS), transmission electron microscope (TEM), and Fourier transform infra-red (FTIR) spectroscope. Nanocapsules were optimized for size and high encapsulation efficiency using central composite design (CCD) software. The encapsulation efficiency of nanocapsules for hexaconazole was 73% as assessed by gas chromatography (GC). Nanocapsules were analysed and compared with commercial formulation for controlled release in vitro at three different pH values. Release of hexaconazole from nanocapsules was fastest at pH 4 in comparison to pH 7 and pH 10. Release study in soil was also conducted and revealed a controlled pattern for nanoformulation. The fungicidal activity of the prepared nanoformulation was evaluated against R. solani and was compared with commercial formulation of hexaconazole. The cytotoxicity assay performed on vero cell lines by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay confirmed that nanoformulation is less toxic than commercial formulation of pesticide., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Toxicology studies have a pivotal role for selection of new nanosystems. As lipid-core nanocapsules (LNC) rise as a potential system not only for drug delivery but also for immunotherapy and gene therapy, the demand for models of toxic screening increases, and sperm arises as a promising model due to the easiness to evaluate its viability parameters. LNCs were coated with chitosan, chitosan-coated lipid-core nanocapsules (LNC-CS), in order to modify the nanocapsule surface. We evaluated the toxicity of LNC and LNC-CS after incubation with bovine sperm in different concentrations (2.5%, 5%, 10%, 20%, 40% and 80%) (v/v) and periods of exposure (0h and 1h). CASA parameters and flow cytometry assays were performed to assess LNC and LNC-CS effects. The results corroborated with previous studies indicating that there is no toxicity from LNCs and LNC-CS below 40% (v/v) concentration., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this work, docetaxel (DTX) was encapsulated in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) micelles and monomethoxy poly(ethylene glycol)-poly(D, L-lactic acid) (mPEG-PLA) micelles, respectively. For the further application, the acute/genetic toxicity evaluation and pharmacokinetic/pharmacodynamic study of the two kinds of micellar nanomedicines were performed. In the study of anticancer activity in vitro and in vivo, DTX micelles showed better tumorgrowth inhibition than free DTX. The pharmacokinetic and tissue distribution studies showed that the DTX incorporated in micelles (especially in DTX-mPEG-PCL) retained significantly higher concentration in plasma and tumor tissue compared with free DTX. The acute toxicity and genotoxicity studies indicated that DTX micelles were safer than the docetaxel injection in cancer therapy and DTX-mPEG-PCL had less damage to DNA than DTX-mPEG-PLA. So the micelles had a pronounced effect on reducing acute toxicity and genotoxicity of docetaxel. In conclusion, DTX micelles were efficient and safe on breast carcinoma chemotherapy.

The aim of this study was to evaluate whether the treatment with Achyrocline satureioides essential oil-loaded in nanocapsules (AS-NC) is able to protect the hepatic tissue against cytotoxic damage caused by Trypanosoma evansi. Thus, the rats were divided into four groups (n = 6 per group): uninfected/saline, uninfected/AS-NC, infected/saline, and infected/AS-NC. At day 4 post-infection (PI), the animals were euthanized and liver and sera samples were collected to perform the hepatic cell viability assay, and to determine seric levels of reactive oxygen species (ROS) and nitric oxide metabolites (NOx). Cell viability decreased (p < 0.05) in the infected/saline group compared to uninfected/saline group, while the treatment with AS-NC avoided this alteration in infected rats. Seric ROS and NOx levels increased (p < 0.05) in the infected/saline group compared to uninfected/saline group, while the treatment with AS-NC avoided this effect on ROS levels of infected rats. In summary, the treatment with AS-NC was able to protect the liver tissue against the cytotoxic effect caused by the parasite by avoiding exacerbated production of ROS., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Triplet-triplet annihilation (TTA)-based upconversion nanocapsules (UCNCs) have great potential in biological and medical applications. However, there are numerous unresolved issues with respect to the safety of these novel nanomaterials. In this work, for the first time, we studied the in vivo biodistribution of UCNCs which were synthesized by co-loading platinum (II)-tetraphenyl-tetrabenzoporphyrin (PtTPBP) and boron dipyrromethene derivative (BDP) into bovine serum albumin (BSA)-stabilized soybean oil droplets, and systematically assessed the potential toxicity of UCNCs both in vitro and in vivo. The results showed that UCNCs had no significant influence on the proliferation or the migration of HeLa cells even when the dosage was increased to 12 mg/mL. The biodistribution results demonstrated that UCNCs mainly accumulated in the mononuclear phagocyte system (MPS) including the liver and spleen after intravenous injection of the nanocapsules. When mice were intravenously injected with 1200 mg/kg of the UCNCs over a period of 60 days, no noticeable toxicity was observed under these treatment conditions as shown by body weight results, histological analyses, hematological analyses and blood biochemical examinations. This research inspires further studies on UCNCs for biomedical applications., (Copyright © 2016. Published by Elsevier Ltd.)

Lutein-poly-(lactic-co-glycolic acid) (PLGA)-phospholipid (PL) nanocapsules were prepared (henceforth referred as lutein nanocapsules) and studied for acute, subacute oral toxicity and bioavailability of lutein in mice. Prior to examining the safety of lutein nanocapsules, particle size, zeta potential, surface morphology and interaction between lutein, PLGA and PL were studied. In acute study, mice were gavaged with a single dose of lutein nanocapsules at 0.1, 1, 10 and 100mg/kg body weight (BW) and examined for 2weeks, while in subacute study, daily mice were gavaged with a dose of 1 and 10mg/kg BW for 4weeks. Results revealed that mean size and zeta value of lutein nanocapsules were 140nm and -44mV, respectively. Acute and subacute toxicity studies did not show any mortality or treatment related adverse effect in clinical observations, ophthalmic examinations, body and organ weights. No toxicity related findings were observed in hematology, histopathology and other blood and tissue clinical chemistry parameters. In subacute study, no observed adverse effect level (NOAEL) of lutein nanocapsules was found to be at a dose of 10mg/kg BW. Feeding lutein nanocapsules resulted in a significant (p<0.01) increase in lutein level in plasma and tissue compared to the control group. Lutein nanocapsules did not cause toxicity in mice. However, human trials are warranted., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Calcitriol (1,25-dihydroxyvitamin D3), an active metabolite of vitamin D3, besides the role in calcium and phosphorus metabolism, plays a role in maintaining the functions of the brain. Active forms of vitamin D3 stimulate neurotrophic factors' expression, regulate brain immune processes, and prevent neuronal damage. Therefore, a potential utility of vitamin D3 in a therapy of neurodegenerative disorders should be taken into account. On the other hand, systemic vitamin D3 treatment carries the risk of undesirable effects, e.g., hypercalcemia. Thus, 1,25-dihydroxyvitamin D3 targeting delivery by nanoparticles would be a tremendous advancement in treatment of brain disorders. Calcitriol was enclosed in emulsion-templated nanocapsules with different polymeric shells: PLL (Poly(L-lysine hydrobromide)), PLL/PGA (/Poly(L-glutamic acid)), and PLL/PGA-g-PEG (Poly(L-glutamic acid) grafted with polyethylene glycol). The average size of all synthesized nanocapsules ranged from -80 to -100 nm. Biocompatibilities of synthesized nanocarriers were examined in hippocampal organotypic cultures in basal conditions and after treatment with lipopolysaccharide (LPS) using various biochemical tests. We demonstrated that nanocapsules coated with PLL were toxic, while PLL/PGA- and PLL/PGA-g-PEG-covered ones were nontoxic and used for further experiments. Our study demonstrated that in LPS-treated hippocampal slices, both types of loaded nanoparticles have protective ability. Our findings underlined that the neuroprotective action of vitamin D3 in both free and nanoparticle forms seems to be related to the suppression of LPS-induced nitric oxide release.

Sustained antigen delivery using incomplete Freund's adjuvant (IFA) can induce strong, long-term immune response, but it can also cause severe side effects. Here we describe an injectable, phospholipid-based phase separation gel (PPSG) that readily transforms in situ into a drug depot. PPSG loaded with the model antigen ovalbumin (OVA) supported sustained OVA release in mice that lasted nearly one month. Immunizing mice with a single injection of PPSG/OVA elicited a strong and persistent increase in titers of OVA-specific IgG, IgG1 and IgG2a. Co-administering CpG-ODN further increased antibody titers. Such co-administration recruited dendritic cells to injection sites and activated dendritic cells in the draining lymph nodes. Moreover, immunization with PPSG/OVA/CpG resulted in potent memory antibody responses and high frequency of memory T cells. Remarkably, PPSG/OVA/CpG was associated with much lower toxicity at injection sites than IFA/OVA/CpG, and it showed no systemic toxicity such as to lymph nodes or spleen. These findings illustrate the potential of injectable PPSG for sustained, minimally toxic delivery of antigens and adjuvants., (Copyright © 2016 Elsevier Ltd. All rights reserved.)