Serum proteins prevent aggregation of Fe2O3 and ZnO nanoparticles

Abstract

Aggregation of metal oxide nanoparticles in aqueous media complicates interpretation of in vitro studies of nanoparticle–cell interactions. We used dynamic light scattering to investigate the aggregation dynamics of iron oxide and zinc oxide nanoparticles. Our results show that iron oxide particles aggregate more readily than zinc oxide particles. Pretreatment with serum stabilises iron oxide and zinc oxide nanoparticles against aggregation. Serum-treated iron oxide is stable only in pure water, while zinc oxide is stable in water or cell culture media. These findings, combined with zeta potential measurements and quantification of proteins adsorbed on particle surface, suggest that serum stabilisation of iron oxide particles occurs primarily through protein adsorption and resulting net surface charge. Zinc oxide stabilisation, however, also involves steric hindrance of particle aggregation. Fluid shear at levels used in flow experiments breaks up iron oxide particle aggregates. These results enhance our understanding of nanoparticle aggregation and its consequences for research on the biological effects of nanomaterials.     

Translocation of 40 nm diameter nanowires through the intestinal epithelium of Daphnia magna

Nanowires (NWs) have unique electrical and optical properties of value for many applications including lighting, sensing, and energy harnessing. Consumer products containing NWs increase the risk of NWs being released in the environment, especially into aquatic ecosystems through sewage systems. Daphnia magna is a common, cosmopolitan freshwater organism sensitive to toxicity tests and represents a likely entry point for nanoparticles into food webs of aquatic ecosystems. Here we have evaluated the effect of NW diameter on the gut penetrance of NWs in Daphnia magna. The animals were exposed to NWs of two diameters (40 and 80?nm) and similar length (3.6 and 3.8?μm, respectively) suspended in water. In order to locate the NWs in Daphnia, the NWs were designed to comprise one inherently fluorescent segment of gallium indium phosphide (GaInP) flanked by a gallium phosphide (GaP) segment. Daphnia mortality was assessed directly after 24?h of exposure and 7 days after exposure. Translocation of NWs across the intestinal epithelium was investigated using confocal fluorescence microscopy directly after 24?h of exposure and was observed in 89% of Daphnia exposed to 40?nm NWs and in 11% of Daphnia exposed to 80?nm NWs. A high degree of fragmentation was observed for NWs of both diameters after ingestion by the Daphnia, although 40?nm NWs were fragmented to a greater extent, which could possibly facilitate translocation across the intestinal epithelium. Our results show that the feeding behavior of animals may enhance the ability of NWs to penetrate biological barriers and that penetrance is governed by the NW diameter.     

Interactions of nanoparticles with plasma proteins: implication on clearance and toxicity of drug delivery systems

Introduction: Intravenously injected nanoparticles, like any other foreign pathogen that enters the body, encounter multiple lines of defense intended to neutralize and eliminate the invading substance. Adsorption of plasma proteins on the nanoparticle surface is the first barrier of defense, which could lead to physical changes in the formulation, such as aggregation and charge neutralization, biochemical activation of defense cascades, and trigger elimination by multiple types of phagocytic cell.

Areas covered: In this review, recent knowledge on the mechanisms that govern the interactions of nanoparticles (micelles, liposomes, polymeric and inorganic nanoparticles) with plasma proteins is discussed. In particular, the role of the nanoparticle surface properties and protective polymer coating in these interactions is described. The mechanisms of protein adsorption on different nanoparticles are analyzed and the implications on the clearance, toxicity and efficacy of drug delivery are discussed. The review provides readers with the biological insight into the plasma/blood interactions of nanoparticles.

Expert opinion: The immune recognition of nanoparticles can seriously affect the drug delivery efficacy and toxicity. There is at present not enough knowledge on the mechanisms that dictate the nanoparticle immune recognition and stability in the biological milieu. Understanding the mechanisms of recognition will become an important part of nanoparticle design.     

Assessment of orally dosed commercial silver nanoparticles on human ex vivo platelet aggregation

Enhanced in vitro human and ex vivo rat platelet aggregation from direct exposure to silver nanoparticles is previously reported. Given the increasing human use of engineered silver nanoscale products, platelet aggregation prompted by silver nanoparticles may contribute to human cardiovascular events. To understand how direct washed platelet exposure to silver nanoparticles translates to ex vivo platelet aggregation, the authors conducted a placebo-controlled, single-blind, dose-monitored, cross-over study design in 18 healthy human volunteers. After 2 weeks of daily oral silver nanoparticle ingestion, platelet aggregation was evaluated by light transmission aggregometry in response to collagen and ADP agonists, both at baseline and after silver nanoparticle or placebo diluent oral dosing. Final percent aggregation (PA) and the changes in PA were determined using a paired design (i.e., active and placebo solutions). Enhanced ex vivo platelet activation was not detectable at peak serum silver concentrations <10 µg/L. Further studies of colloidal silver nanoparticles on human platelet activities are warranted.     

Protein corona formation in bronchoalveolar fluid enhances diesel exhaust nanoparticle uptake and pro-inflammatory responses in macrophages

In biological fluids nanoparticles bind a range of molecules, particularly proteins, on their surface. The resulting protein corona influences biological activity and fate of nanoparticle in vivo. Corona composition is often determined by the biological milieu encountered at the entry portal into the body, and, can therefore, depend on the route of exposure to the nanoparticle. For environmental nanoparticles where exposure is by inhalation, this will be lung lining fluid.

This study examined plasma and bronchoalveolar fluid (BALF) protein binding to engineered and environmental nanoparticles. We hypothesized that protein corona on nanoparticles would influence nanoparticle uptake and subsequent pro-inflammatory biological response in macrophages.

All nanoparticles bound plasma and BALF proteins, but the profile of bound proteins varied between nanoparticles. Focusing on diesel exhaust nanoparticles (DENP), we identified proteins bound from plasma to include fibrinogen, and those bound from BALF to include albumin and surfactant proteins A and D. The presence on DENP of a plasma-derived corona or one of purified fibrinogen failed to evoke an inflammatory response in macrophages. However, coronae formed in BALF increased DENP uptake into macrophages two fold, and increased nanoparticulate carbon black (NanoCB) uptake fivefold. Furthermore, a BALF-derived corona increased IL-8 release from macrophages in response to DENP from 1720?±?850?pg/mL to 5560?±?1380?pg/mL (p?=?0.014). These results demonstrate that the unique protein corona formed on nanoparticles plays an important role in determining biological reactivity and fate of nanoparticle in vivo. Importantly, these findings have implications for the mechanism of detrimental properties of environmental nanoparticles since the principle route of exposure to such particles is via the lung.     

Effects of aggregation and the surface properties of gold nanoparticles on cytotoxicity and cell growth

The effect of gold nanoparticles (Au NPs) on cells remains open for investigation. Here we show that small Au NPs can be endocytosed by cells and form aggregates inside the cell, resulting in cytotoxicity. When the aggregates become too large to enter the cell and instead adhere onto the cell surface, however, the growth rate of HeLa cells increases. Printed patterns of Au NPs fabricated through inkjet printing technology were used to study the effects of Au NP aggregation on human cervical carcinoma (HeLa) cell activity. The growth of the HeLa cells was inhibited on the polymer-coated Au NPs but increased on the silicon substrate. On the uncoated Au NP surface, however, the HeLa cell growth rate was higher than that on the silicon substrate. Experiments with Escherichia coli cells showed a similar effect of the Au NPs. This phenomenon provides a new perspective for research on toxicity in nanoparticle biology. FROM THE CLINICAL EDITOR: Printed patterns of Au NPs fabricated through inkjet printing technology were used to study the effects of Au NP aggregation on human cervical carcinoma (HeLa) cell activity. Small Au NPs can be endocytosed by cells resulting in cytotoxicity; in contrast, large aggregates adhere onto the cell surface and increase the growth rate of HeLa cells.     

Nanoparticles laden in situ gel of levofloxacin for enhanced ocular retention

Abstract

Availability of proper concentration of medicament on to the corneal surface is a challenging task. Many novel formulations, i.e. hydrogels, nanoparticles, ocuserts, etc. had been tested to improve ocular bioavailability, out of which our group found, in situ gel and polymeric nanoparticle are the most interesting approach to achieve ocular retention. We found that in situ gel stay only for 12?h and poly(lactic-co-glycolic acid (PLGA) nanoparticles are non mucoadhesive in nature so we try to combine both these formulations and termed it as “Nanoparticle laden in situ gel”. Here we prepare nanoparticle laden in situ gel containing levofloxacin encapsulated PLGA nanoparticle, incorporated in chitosan in situ gel and evaluated its ocular retention by gamma scintigraphy in rabbits. The observations of acquired gamma camera images showed good retention over the entire precorneal area. From static and dynamic gamma scintigraphy evaluation, we can be interpret that developed nanoparticle laden in situ gel formulation cleared at a very slow rate and remained at corneal surface for longer duration than marketed formulation, in situ gel and nanosuspension alone.     

The importance of nanoparticle shape in cancer drug delivery

Introduction: Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy.

Areas covered: This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and overall drug efficacy. By comparing spherical and nonspherical nanoparticles, they establish some general design principles to serve as guidelines for developing the next generation of nanocarriers for drug delivery.

Expert opinion: Pioneering studies on nanoparticles show that nonspherical shapes show great promise as cancer drug delivery vectors. Filamentous or worm-like micelles together with other rare morphologies such as needles or disks may become the norm for next-generation drug carriers, though at present, traditional spherical micelles remain the dominant shape of nanocarriers described in the literature due to synthesis and testing difficulties. The few reports that do exist describing nonspherical nanoparticles show a number of favorable properties that should encourage more efforts to develop facile and versatile nanoparticle synthesis methodologies with the flexibility to create different shapes, tunable sizes and adaptable surface chemistries. In addition, the authors note that there is a current lack of understanding into the factors governing (and optimizing) the inter-relationships of size, surface characteristics and shapes of many nanoparticles proposed for use in cancer therapy.     

Electron microscopy of gold nanoparticle intake in the gut of Daphnia magna

Few studies have described aquatic organisms interacting with manufactured nanoparticles. One key factor in determining these materials potential toxicity is the extent to which these particles accumulate in tissues. This may be most important for aquatic organisms as they contact large quantities of water through their feeding behavior. We examined the uptake and release of gold particles in filter-feeding Daphnia magna. Daphnia were exposed to sublethal concentrations of gold nanoparticles for 1, 6, 12, or 24 hours. Transmission Electron Microscopy was used to examine the presence and distribution of gold in gut tissue. The highest concentration of nanoparticles was found after 12 h. Particle clearance was investigated by placing organisms in fresh water and observing particles retention in the gut tissue over time. The initial trend of high gold concentration in the mouth with low levels in the tail region was reversed, suggesting clearance of particles with time.     

An assessment of the importance of exposure routes to the uptake and internal localisation of fluorescent nanoparticles in zebrafish (Danio rerio), using light sheet microscopy

A major challenge in nanoecotoxicology is finding suitable methods to determine the uptake and localisation of nanoparticles on a whole-organism level. Some uptake methods have been associated with artefacts induced by sample preparation, including staining for electron microscopy. This study used light sheet microscopy (LSM) to define the uptake and localisation of fluorescently labelled nanoparticles in living organisms with minimal sample preparation. Zebrafish (Danio rerio) were exposed to fluorescent gold nanoparticles (Au NPs) and fluorescent polystyrene NPs via aqueous or dietary exposure. The in vivo uptake and localisation of NPs were investigated using LSM at different time points (1, 3 and 7?days). A time-dependent increase in fluorescence was observed in the gut after dietary exposure to both Au NPs and polystyrene NPs. No fluorescence was observed within gut epithelia regardless of the NP exposure route indicating no or limited uptake via intestinal villi. Fish exposed to polystyrene NPs through the aqueous phase emitted fluorescence signals from the gills and intestine. Fluorescence was also detected in the head region of the fish after aqueous exposure to polystyrene NPs. This was not observed for Au NPs. Aqueous exposure to Au NPs resulted in increased relative swimming distance, while no effect was observed for other exposures. This study supports that the route of exposure is essential for the uptake and subsequent localisation of nanoparticles in zebrafish. Furthermore, it demonstrates that the localisation of NPs in whole living organisms can be visualised in real-time, using LSM.     

Effects of nickel-oxide nanoparticle pre-exposure dispersion status on bioactivity in the mouse lung

Nanotechnology is emerging as one of the world's most promising new technologies. From a toxicology perspective, nanoparticles possess two features that promote their bioactivity. The first involves physical–chemical characteristics of the nanoparticle, which include the surface area of the nanoparticle. The second feature is the ability of the nanoparticle to traverse cell membranes. These two important nanoparticle characteristics are greatly influenced by placing nanoparticles in liquid medium prior to animal exposure. Nanoparticles tend to agglomerate and clump in suspension, making it difficult to reproducibly deliver them for in vivo or in vitro experiments, possibly affecting experimental variability. Thus, we hypothesize that nanoparticle dispersion status will correlate with the in vivo bioactivity/toxicity of the particle. To test our hypothesis, nano-sized nickel oxide was suspended in four different dispersion media (phosphate-buffered saline (PBS), dispersion medium (DM), a combination of dipalmitoyl-phosphatidyl choline (DPPC) and albumin in concentrations that mimic diluted alveolar lining fluid), Survanta®, or pluronic (Pluronic F-68). Well-dispersed and poorly dispersed suspensions were generated in each media by varying sonication time on ice utilizing a Branson Sonifer 450 (25W continuous output, 20?min or 5?min, respectively). Mice (male, C57BL/6J, 7-weeks-old) were given 0–80?µg/mouse of nano-sized nickel oxide in the different states of dispersion via pharyngeal aspiration. At 1 and 7 d post-exposure, mice underwent whole lung lavage to assess pulmonary inflammation and injury as a function of dispersion status, dose and time. The results show that pre-exposure dispersion status correlates with pulmonary inflammation and injury. These results indicate that a greater degree of pre-exposure dispersion increases pulmonary inflammation and cytotoxicity, as well as decreases in the integrity of the blood–gas barrier in the lung.     

Salmon calcitonin-loaded Eudragit® and Eudragit®-PLGA nanoparticles: in vitro and in vivo evaluation

The main objective of this study was to prepare salmon calcitonin (sCT)-loaded Eudragit®RSPO, Eudragit®L100 and Eudragit®-poly(lactic-co-glycolic acid) blend nanoparticles for in vitro and in vivo evaluation as an oral drug delivery system. The prepared nanoparticles ranged in size from 179.7 to 308.9?nm with a polydispersity index between 0.051 and 2.75, and had surface charges ? ?11 to +6?mV. Efficient sCT encapsulation and release was observed with all the nanoparticle formulations. The polymer type was an important factor that influenced the release characteristics and the in vivo hypocalcemic effect. Nanoparticle formulations were also prepared with sodium taurodeoxycholate (NaTDC) and characterized. No statistically significant difference was noted between the hypocalcemic effect of any of the nanoparticle formulations with and without NaTDC (p?>?0.05). The use of Eudragit®RSPO nanoparticles appears to be a potential approach for the oral delivery of sCT.     

Nanoparticles: structure,properties, preparation and behaviour in environmental media

There is increasing interest and need to develop a deeper understanding of the nature, fate and behaviour of nanoparticles in the environment. This is driven by the increased use of engineered nanoparticles and the increased pressure to commercialise this growing technology. In this review we discuss the key properties of nanoparticles and their preparation and then discuss how these factors can play a role in determining their fate and behaviour in the natural environment. Key focus of the discussion will relate to the surface chemistry of the nanoparticle, which may interact with a range of molecules naturally present in surface waters and sediments. Understanding these factors is a core goal required for understanding the final fate of nanomaterials and predicting which organisms are likely to be exposed to these materials.     

Silver nanoparticle toxicity is related to coating materials and disruption of sodium concentration regulation

Silver nanoparticles (AgNPs) have been increasingly commercialized and their release into the environment is imminent. Toxicity of AgNP has been studied with a wide spectrum of organisms, yet the mechanism of toxicity remains largely unknown. This study systematically compared toxicity of 10 AgNPs of different particle diameters and coatings to Japanese medaka (Oryzias latipes) larvae to understand how characteristics of AgNP relate to toxicity. Dissolution of AgNPs was largely dependent on particle size, but their aggregation behavior and toxicity were more dependent on coating materials. 96?h lethal concentration 50% (LC50) values correlated with AgNP aggregate size rather than size of individual nanoparticles. Of the AgNPs studied, the dissolved Ag concentration in the test suspensions did not account for all of the observed toxicity, indicating the role of NP-specific characteristics in resultant toxicity. Exposure to AgNP led to decrease of sodium concentration in the tissue and increased expression of Na⁺/K^+?ATPase. Gene expression patterns also suggested that toxicity was related to disruption of sodium regulation and not to oxidative stress.     

Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity

Abstract

Inhaled nanomaterials present a challenge to traditional methods and understanding of respiratory toxicology. In this study, a non-targeted metabolomics approach was used to investigate relationships between nanoparticle hydrophobicity, inflammatory outcomes and the metabolic fingerprint in bronchoalveolar fluid. Measures of acute lung toxicity were assessed following single-dose intratracheal administration of nanoparticles with varying surface hydrophobicity (i.e. pegylated lipid nanocapsules, polyvinyl acetate nanoparticles and polystyrene beads; listed in order of increasing hydrophobicity). Broncho-alveolar lavage (BAL) fluid was collected from mice exposed to nanoparticles at a surface area dose of 220?cm² and metabolite fingerprints were acquired via ultra pressure liquid chromatography-mass spectrometry-based metabolomics. Particles with high surface hydrophobicity were pro-inflammatory. Multivariate analysis of the resultant small molecule fingerprints revealed clear discrimination between the vehicle control and polystyrene beads (p?<?0.05), as well as between nanoparticles of different surface hydrophobicity (p?<?0.0001). Further investigation of the metabolic fingerprints revealed that adenosine monophosphate (AMP) concentration in BAL correlated with neutrophilia (p?<?0.01), CXCL1 levels (p?<?0.05) and nanoparticle surface hydrophobicity (p?<?0.001). Our results suggest that extracellular AMP is an intermediary metabolite involved in adenine nucleotide-regulated neutrophilic inflammation as well as tissue damage, and could potentially be used to monitor nanoparticle-induced responses in the lung following pulmonary administration.     

Surface loading of nanoparticles on engineered or natural erythrocytes for prolonged circulation time: strategies and applications

Nano drug-delivery systems (DDS) may significantly improve efficiency and reduce toxicity of loaded drugs, but a few nano-DDS are highly successful in clinical use. Unprotected nanoparticles in blood flow are often quickly cleared, which could limit their circulation time and drug delivery efficiency. Elongating their blood circulation time may improve their delivery efficiency or grant them new therapeutic possibilities. Erythrocytes are abundant endogenous cells in blood and are continuously renewed, with a long life span of 100–120 days. Hence, loading nanoparticles on the surface of erythrocytes to protect the nanoparticles could be highly effective for enhancing their in vivo circulation time. One of the key questions here is how to properly attach nanoparticles on erythrocytes for different purposes and different types of nanoparticles to achieve ideal results. In this review, we describe various methods to attach nanoparticles and drugs to the erythrocyte surface, and discuss the key factors that influence the stability and circulation properties of the erythrocytes-based delivery system in vivo. These data show that using erythrocytes as a host for nanoparticles possesses great potential for further development.Keyword: drug delivery systems, nanoparticle, erythrocytes, prolonged circulation time     

Gold nanoparticle conjugates: recent advances toward clinical applications

Introduction: Gold nanoparticles display a unique combination of chemical inertness, surface chemistry and size- and shape-dependent electronic and optical properties, which render them ideal for clinical applications.

Areas covered: The present article describes recent advancements on the application of gold nanoparticles in vaccine development and gene therapy, with augmented efficiencies in cell uptake, specific binding to bioreceptors in cells, protection of conjugated biomolecules and so forth. Additionally, we discuss how the electronic structure of the nanoparticles can be exploited for enhanced radiotherapy and X-ray tomography, while their optical properties can be used for photothermal cancer therapy or light-triggered drug delivery systems for enhanced chemotherapy.

Expert opinion: We analyze certain critical aspects and possible challenges that should be solved in order to use gold nanoparticle conjugates in vaccine research, as well as on the potential combination of properties to improve gene therapy and cancer treatment.     

Role of purinergic receptors in platelet-nanoparticle interactions

Primary objective. Elevation of the thrombotic responses mediated by a variety of carbon-derived nanoparticles was recently reported in the literature. In this paper our objective was to investigate whether metal nanoparticles (iron, copper, gold or cadmium sulfide [CdS]) impart such prothrombotic effects on human platelets. Secondly, we wanted to examine whether such effects were mediated through any specific platelet receptor. Experimental design. The size distributions and zeta potentials of characterized gold, copper, iron and CdS (rod & sphere) nanoparticles were measured using photon correlation spectroscopy and laser Doppler velocimetry. The effect of two classes of agonists, adenosine diphosphate (ADP) and epinephrine were studied. To study the effect of ADP, a suboptimal concentration was chosen below a critical concentration. Above the critical concentration, the aggregation assumed its standard hyperbolic shape (and de-aggregation disappeared). Pro-aggregatory action of a given agent can be understood with better sensitivity using a transition from deaggregation to aggregation at this suboptimal agonist level. For epinephrine at low concentration this criticality was absent, however the aggregatory profile showed a delayed response. Two classes of human subjects (a) normal and (b) individuals with acute coronary syndrome, who were under a therapeutic regime of clopidogrel were chosen, as clopidogrel is a specific inhibitor of the low affinity ADP receptor P2Y12. This enabled us to understand the pro-aggregatory effects of nanoparticles with only P2Y1 (high affinity ADP receptor) active. In another set of aggregation experiments, the inhibitor MRS2179 was used to specifically block the high affinity ADP receptor P2Y1. Methods. The threshold ADP concentration was determined using an ADP titration. Nanoparticle rich platelet suspensions were exposed to a previously determined sub-optimal ADP concentration. The experiment was repeated with iron, copper, gold and CdS nanoparticles (later with two different morphologies, rod and sphere). Results. The primary result was that the nanoparticles, composed of various materials and shape features, are likely to impart a pro-aggregatory response in platelets. That the pro-aggregatory effect is not solely a physical self-assembly process and has ADP dependence, is evident from the reversal of the said response by apyrase. The fact that the response was absent in the case of P2Y12 blocked subjects (CdS nanoparticles being an exception) suggests that the low-affinity P2Y12 receptor may be an important target for the nanoparticles. If on the other hand P2Y1 (the high affinity receptor) was blocked by the specific inhibitor MRS2179, nanoparticles could still induce higher aggregation in normal subjects. No significant nanoparticle induced proaggregatory effect was observed for epinephrine. Inference. It is inferred, that the said platelet effect is mediated through ADP receptors, the probable target being the low affinity purinergic receptor P2Y12. The indication is that P2Y12 is a potential target for a wide class of nanoparticles. However the extent of the induced pro-aggregatory effect may be dependent upon the constitutive material and/or the shape of the nanoparticles. This may have important implications in the use of nano-materials in human drug delivery systems. The fact that clopidogrel prevents this nanoparticle mediated prothrombotic effect (with CdS as an exception) may help making nanodrug administration safer.     

Preparation and optimization of N-trimethyl-O-carboxymethyl chitosan nanoparticles for delivery of low-molecular-weight heparin

The aim of this study was preparation, optimization and in vitro characterization of nanoparticles composed of 6-[O-carboxymethyl]-[N,N,N-trimethyl] (TMCMC) for oral delivery of low-molecular-weight heparin. The chitosan derivative was synthesized. Nanoparticles were prepared using the polyelectrolyte complexation method. Box–Behnken response surface experimental design methodology was used for optimization of nanoparticles. The morphology of nanoparticles was studied using transmission electron microscopy. In vitro release of enoxaparin from nanoparticles was determined under simulated intestinal fluid. The cytotoxicity of nanoparticles on a Caco-2 cell line was determined, and finally the transport of prepared nanoparticles across Caco-2 cell monolayer was defined. Optimized nanoparticles with proper physico-chemical properties were obtained. The size, zeta potential, poly-dispersity index, entrapment efficiency and loading efficiency of nanoparticles were reported as 235?±?24.3?nm, +18.6?±?2.57?mV, 0.230?±?0.03, 76.4?±?5.43% and 12.6?±?1.37%, respectively. Morphological studies revealed spherical nanoparticles with no sign of aggregation. In vitro release studies demonstrated that 93.6?±?1.17% of enoxaparin released from nanoparticles after 600?min of incubation. MTT cell cytotoxicity studies showed no cytotoxicity at 3?h post-incubation, while the study demonstrated concentration-dependent cytotoxicity after 24?h of exposure. The obtained data had shown that the nanoparticles prepared from trimethylcarboxymethyl chitosan may be considered as a good candidate for oral delivery of enoxaparin.     

No evidence of the genotoxic potential of gold,silver, zinc oxide and titanium dioxide nanoparticles in the SOS chromotest

Gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO₂ NPs) are widely used in cosmetic products such as preservatives, colorants and sunscreens. This study investigated the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO₂ NPs using the SOS chromotest with Escherichia coli PQ37. The maximum exposure concentrations for each nanoparticle were 3.23 mg l^–1 for Au NPs, 32.3 mg l^–1 for Ag NPs and 100 mg l^–1 for ZnO NPs and TiO₂ NPs. Additionally, in order to compare the genotoxicity of nanoparticles and corresponding dissolved ions, the ions were assessed in the same way as nanoparticles. The genotoxicity of the titanium ion was not assessed because of the extremely low solubility of TiO₂ NPs. Au NPs, Ag NPs, ZnO NPs, TiO₂ NPs and ions of Au, Ag and Zn, in a range of tested concentrations, exerted no effects in the SOS chromotest, evidenced by maximum IF (IFmax) values of below 1.5 for all chemicals. Owing to the results, nanosized Au NPs, Ag NPs, ZnO NPs, TiO₂ NPs and ions of Au, Ag and Zn are classified as non‐genotoxic on the basis of the SOS chromotest used in this study. To the best of our knowledge, this is the first study to evaluate the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO₂ NPs using the SOS chromotest. Copyright © 2012 John Wiley & Sons, Ltd.