Evidence and hypotheses on adverse effects of the food additives carrageenan (E 407)/processed Eucheuma seaweed (E 407a) and carboxymethylcellulose (E 466) on the intestines: a scoping review.

This scoping review provides an overview of publications reporting adverse effects on the intestines of the food additives carrageenan (CGN) (E 407)/processed Eucheuma seaweed (PES) (E 407a) and carboxymethylcellulose (CMC) (E 466). It includes evidence from human, experimental mammal and in vitro research publications, and other evidence. The databases Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Database of Systematic Reviews and Epistemonikos were searched without time limits, in addition to grey literature. The publications retrieved were screened against predefined criteria. From two literature searches, 2572 records were screened, of which 224 records were included, as well as 38 records from grey literature, making a total of 262 included publications, 196 on CGN and 101 on CMC. These publications were coded and analyzed in Eppi-Reviewer and data gaps presented in interactive maps. For CGN, five, 69 and 33 research publications on humans, experimental mammals and in vitro experiments were found, further separated as degraded or native (non-degraded) CGN. For CMC, three human, 20 animal and 14 in vitro research publications were obtained. The most studied adverse effects on the intestines were for both additives inflammation, the gut microbiome, including fermentation, intestinal permeability, and cancer and metabolic effects, and immune effects for CGN. Further studies should focus on native CGN, in the form and molecular weight used as food additive. For both additives, randomized controlled trials of sufficient power and with realistic dietary exposure levels of single additives, performed in persons of all ages, including potentially vulnerable groups, are needed.

Sequestration and toxicological assessment of emerging contaminants with polypyrrole modified carboxymethyl cellulose (CMC/PPY): Case of ibuprofen pharmaceutical drug.

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug released into water bodies causing toxic biological effects on living organisms. The current study aims to eliminate IBU from aqueous solutions by a novel carboxymethylcellulose/polypyrrole (CMC/PPY) composite with high removal efficiency. Pyrrole was polymerized to polypyrrole whose average size was about 20 nm on the CMC surface. The maximum removal percentage of IBU by CMC/PPY composite was optimized at initial concentration 10 mg/L, dosage 0.02 g, and pH 7 with adsorption capacity of 72.30 (mg/g) and removal of 83.17 %. IBU adsorption onto CMC/PPY theoretically fits into the Langmuir isotherm and Elovich-kinetic models. Fish and Phytotoxicity assessment were performed with zebrafish and seeds of Vigna mungo (VM) and Vigna radiata (VR). The toxicity study reveals that before adsorption, IBU shows high toxicity towards the zebrafish mortality (33 %), growth inhibition (58.52 % for VM, 60.84 % for VR), and germination (86.66 % for VM and 90 % for VR). As CMC/PPY adsorbs IBU, toxicity drastically decreases. Before adsorption, LC50 was 233.02 mg/L. After adsorption, the LC50 increases to 2325.07 mg/L as IBU molecules get adsorbed by CMC/PPY. These findings show the feasibility of preparing CMC/PPY composite to effectively remove pharmaceutical pollutant IBU from aqueous solutions with their toxicological assessment.

Toxicological studies and some functional properties of carboxymethylated cellulose nanofibrils as potential food ingredient.

Carboxymethylated cellulose nanofibrils (CNF) with different carboxyl contents (0, 0.36, 0.72 and 1.24 mmol/g) were prepared and characterized via morphology, diameter distribution, zeta potential, structural features, rheological properties, suspension stability, and thermal properties. The results of toxicological studies of ingested CNF via in vitro and in vivo models were present. In vitro studies used an epithelial-like cell line (Caco-2) to assess the effects of a 24 h incubation with CNF, in which no significant cytotoxicity was observed. In vivo studies were evaluated in mice gavage once per day for 8 weeks with 1% or 3.5% w/w suspension of CNF in water. Blood and serum were collected for analysis. No significant differences in hematology, and serum markers were observed between controls and mice given CNF suspensions. Weight, food intake and feces were recorded for growing development and nutrient retention in feces was measured for investigation of functional properties of CNFs. Mice given CNF suspensions gained a significant increment in fecal fat but a reduction in food intake and weight compared to controls. These findings suggested that CNFs are non-toxic and have potentials in behaving as food additives or supplements to reduce caloric intake.

Hybrid Bionanocomposite Containing Magnesium Hydroxide Nanoparticles Embedded in a Carboxymethyl Cellulose Hydrogel Plus Silk Fibroin as a Scaffold for Wound Dressing Applications.

Based on the promising biomedical developments in wound healing strategies, herein, a new nanobiocomposite scaffold was designed and presented by incorporation of carboxymethyl cellulose hydrogels prepared using epichlorohydrin as a cross-linking agent (CMC hydrogel), a natural silk fibroin (SF) protein, and magnesium hydroxide nanoparticles (Mg(OH)2 NPs). Biological evaluation of the CMC hydrogel/SF/Mg(OH)2 nanobiocomposite scaffold was conducted via in vitro cell viability assays and in vivo assays, red blood cell hemolysis, and antibiofilm assays. Considering the cell viability percentage of Hu02 cells (84.5%) in the presence of the prepared nanobiocomposite after 7 days, it was indicated that this new nanoscaffold was biocompatible. The signs of excellent hemocompatibility and the high antibacterial activity were observed due to the low-point hemolytic effect (8.3%) and high-level potential in constraining the P. aeruginosa biofilm formation with a low OD value (0.13). Moreover, in vivo wound healing assay results indicated that the wound healing method was faster in mice treated with the prepared nanobiocomposite scaffold (82.29%) than the control group (75.63%) in 12 days. Apart from the structural characterization of the CMC hydrogel/SF/Mg(OH)2 nanobiocomposite through FTIR, EDX, FESEM, and TG analyses, compressive mechanical tests, contact angle, porosity, and swelling ratio studies indicated that the combination of the CMC hydrogel structure with SF protein and Mg(OH)2 NPs could significantly impact Young's modulus (from 11.34 to 10.14 MPa), tensile strength (from 299.35 to 250.78 MPa), elongation at break (12.52 to 12.84%), hydrophilicity, and water uptake capacity (92.5%).

Sulfated carboxymethylcellulose conjugated electrospun fibers as a growth factor presenting system for tissue engineering.

Inspired by the natural electrostatic interaction of cationic growth factors with anionic sulfated glycosaminoglycans in the extracellular matrix, we developed electrospun poly(hydroxybutyrate)/gelatin (PG) fibers conjugated with anionic sulfated carboxymethylcellulose (sCMC) to enable growth factor immobilization via electrostatic interaction for tissue engineering. The fibrous scaffold bound cationic molecules, was cytocompatible and exhibited a remarkable morphological and functional stability. Transforming growth factor-ß1 immobilized on the sCMC conjugated fibers was retained for at least 4 weeks with negligible release (3%). Immobilized fibroblast growth factor-2 and connective tissue growth factor were bioactive and induced proliferation and fibrogenic differentiation of infrapatellar fat pad derived mesenchymal stem cells respectively with efficiency similar to or better than free growth factors. Taken together, our studies demonstrate that sCMC conjugated PG fibers can immobilize and retain function of cationic growth factors and hence show potential for use in various tissue engineering applications.

Dose- and time-dependent systemic adverse reactions of sodium carboxy methyl cellulose after intraperitoneal application in rats.

Sodium carboxy methyl cellulose (SCMC) is an important absorbable biomaterial for anti-adhesion and hemostasis medical devices used in the abdominal cavity. However, the systemic toxicity of SCMC following intraperitoneal route has not been revealed sufficiently. Three SCMC solutions with gradient concentrations were intraperitoneally injected into 3 groups of rats with the doses of 50 mg/kg, 320 mg/kg and 2000 mg/kg respectively all at once to observe the dose-dependence of systemic reactions of SCMC and 10 rats (5 rats per sex) of each group were sacrificed 3 days, 7 days, 28 days and 90 days after injection to evaluate the time-dependence of the reactions. A range of adverse effects were shown in rats of the high-dose group which were found varied with time extending and virtually disappeared 90 days after injection. Slight reactions were observed in the medium-dose group while negligible effects were found in the low-dose group. The intraperitoneal application of SCMC can induce reversible systemic adverse effects to rats at the dose higher than 320 mg/kg and it is essential to take both dose- and time-dependent effects into account while designing a systemic toxicity study for absorbable biomaterials.

Sonochemical preparation of folate-decorated reductive-responsive carboxymethylcellulose-based nanocapsules for targeted drug delivery.

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.

Analysis of In Vitro Cytotoxicity of Carbohydrate-Based Materials Used for Dissolvable Microneedle Arrays.

PURPOSE: Dissolvable microneedle arrays (MNAs) can be used to realize enhanced transdermal and intradermal drug delivery. Dissolvable MNAs are fabricated from biocompatible and water-soluble base polymers, and the biocargo to be delivered is integrated with the base polymer when forming the MNAs. The base polymer is selected to provide mechanical strength, desired dissolution characteristics, and compatibility with the biocargo. However, to satisfy regulatory requirements and be utilized in clinical applications, cytotoxicity of the base polymers should also be thoroughly characterized. This study systematically investigated the cytotoxicity of several important carbohydrate-based base polymers used for production of MNAs, including carboxymethyl cellulose (CMC), maltodextrin (MD), trehalose (Treh), glucose (Gluc), and hyaluronic acid (HA). METHODS: Each material was evaluated using in vitro cell-culture methods on relevant mouse and human cells, including MPEK-BL6 mouse keratinocytes, NIH-3T3 mouse fibroblasts, HaCaT human keratinocytes, and NHDF human fibroblasts. A common laboratory cell line, human embryonic kidney cells HEK-293, was also used to allow comparisons to various cytotoxicity studies in the literature. Dissolvable MNA materials were evaluated at concentrations ranging from 3 mg/mL to 80 mg/mL. RESULTS: Qualitative and quantitative analyses of cytotoxicity were performed using optical microscopy, confocal fluorescence microscopy, and flow cytometry-based assays for cell morphology, viability, necrosis and apoptosis. Results from different methods consistently demonstrated negligible in vitro cytotoxicity of carboxymethyl cellulose, maltodextrin, trehalose and hyaluronic acid. Glucose was observed to be toxic to cells at concentrations higher than 50 mg/mL. CONCLUSIONS: It is concluded that CMC, MD, Treh, HA, and glucose (at low concentrations) do not pose challenges in terms of cytotoxicity, and thus, are good candidates as MNA materials for creating clinically-relevant and well-tolerated biodissolvable MNAs.

High foliar affinity cellulose for the preparation of efficient and safe fipronil formulation.

In this work, fipronil was encapsulated within ethanediamine-modified carboxymethylcellulose (ACMC) to prepare an efficient and environmentally safe pesticide formulation (ACMCF). The chemical structure, morphology, foliar adhesion, bioactivity, and soil mobility of ACMCF were also systematically investigated. Results demonstrated that fipronil was encapsulated to form microcapsules successfully. Compared with the traditional fipronil emulsion (FE), ACMCF had a relatively high retention rate on cucumber and peanut leaves. The acute contact toxicity of ACMCF (LD50 = 0.151 µg a.i./bee) toward Apis mellifera was far lower than that of FE (LD50 = 0.00204 µg a.i./bee). Biological activity surveys confirmed that ACMCF has insecticidal ability against Plutella xylostella similar to that of FE. Moreover, the leaching and migration properties of ACMCF in three different kinds soils were weaker than those of FE. These results imply that ACMCF has promising application potential in increasing the effective utilization of fipronil and reducing risk to non-target organisms and the environment.

Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model.

PURPOSE: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems. METHODS: A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues. RESULTS: The physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization. CONCLUSION: Chemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.

Dietary emulsifiers consumption alters anxiety-like and social-related behaviors in mice in a sex-dependent manner.

Dietary emulsifiers carboxylmethylcellulose (CMC) and polysorbate 80 (P80) alter the composition of the intestinal microbiota and induce chronic low-grade inflammation, ultimately leading to metabolic dysregulations in mice. As both gut microbiota and intestinal health can influence social and anxiety-like behaviors, we investigated whether emulsifier consumption would detrimentally influence behavior. We confirmed that emulsifier exposure induced chronic intestinal inflammation, increased adiposity, and altered gut microbiota composition in both male and female mice, although the specific microboal taxa altered following emulsifier consumption occurred in a sex-dependent manner. Importantly, emulsifier treatment altered anxiety-like behaviors in males and reduced social behavior in females. It also changed expression of neuropeptides implicated in the modulation of feeding as well as social and anxiety-related behaviors. Multivariate analyses revealed that CMC and P80 produced distinct clustering of physiological, neural, and behavioral effects in male and female mice, suggesting that emulsifier treatment leads to a syndrome of sex-dependent changes in microbiota, physiology, and behavior. This study reveals that these commonly used food additives may potentially negatively impact anxiety-related and social behaviors and may do so via different mechanisms in males and females.

Impact of surface modification on the toxicity of zerovalent iron nanoparticles in aquatic and terrestrial organisms.

Nanoscale zerovalent iron (nZVI)-based materials are increasingly being applied in environmental remediation, thereby lead to their exposure to aquatic and terrestrial biota. However, little is known regarding the toxic effects of surface-modified nZVI on multiple species in the ecosystem. In this study, we systematically compared the toxicities of different forms of nZVIs, such as bare nZVI, carboxymethyl cellulose (CMC)-stabilized nZVI, tetrapolyphosphate (TPP)-coated nZVI and bismuth (Bi)-doped nZVI, on a range of aquatic and terrestrial organisms, including bacteria (Escherichia coli and Bacillus subtilis), plant (Arabidopsis thaliana), water flea (Daphnia magna) and earthworm (Eisenia fetida). The Bi- and CMC-nZVI induced adverse biological responses across all the test systems, except E. fetida, varying from cell death in E. coli and B. subtilis to inhibition of the physiological states in D. magna and A. thaliana. The particle characterization under exposure conditions indicated that the surface modification of nZVI played a significant role in their toxicities by changing their physicochemical properties. The underlying mechanisms by which nZVI induces toxicity might be a combination of oxidative stress and another mechanism such as cell membrane disruption, chlorosis and hypoxia. Overall, our findings could provide important implications for the development of environment-friendly nanomaterials and direct further ecotoxicological researches regarding interspecies exploration.

Toxicity and Transcriptome Sequencing (RNA-seq) Analyses of Adult Zebrafish in Response to Exposure Carboxymethyl Cellulose Stabilized Iron Sulfide Nanoparticles.

Increasing utilization of stabilized iron sulfides (FeS) nanoparticles implies an elevated release of the materials into the environment. To understand potential impacts and underlying mechanisms of nanoparticle-induced stress, we used the transcriptome sequencing (RNA-seq) technique to characterize the transcriptomes from adult zebrafish exposed to 10 mg/L carboxymethyl cellulose (CMC) stabilized FeS nanoparticles for 96 h, demonstrating striking differences in the gene expression profiles in liver. The exposure caused significant expression alterations in genes related to immune and inflammatory responses, detoxification, oxidative stress and DNA damage/repair. The complement and coagulation cascades Kyoto encyclopedia of genes and genomes (KEGG) pathway was found significantly up-regulated under nanoparticle exposure. The quantitative real-time polymerase chain reaction using twelve genes confirmed the RNA-seq results. We identified several candidate genes commonly regulated in liver, which may serve as gene indicators when exposed to the nanoparticles. Hepatic inflammation was further confirmed by histological observation of pyknotic nuclei, and vacuole formation upon exposure. Tissue accumulation tests showed a 2.2 times higher iron concentration in the fish tissue upon exposure. This study provides preliminary mechanistic insights into potential toxic effects of organic matter stabilized FeS nanoparticles, which will improve our understanding of the genotoxicity caused by stabilized nanoparticles.

Cytotoxic and genotoxic effects of silver nanoparticle/carboxymethyl cellulose on Allium cepa.

Several mutagenic agents may be present in substances released in the environment, which may cause serious environmental impacts. Among these substances, there is a special concern regarding the widespread use of silver nanoparticles (AgNP) in several products due to their widely known bactericidal properties, including in the medical field and the food industry (e.g., active packaging). The assessment of the effects of AgNP released in the environment, having different concentrations, sizes, and being associated or not to other types of materials, including polymers, is therefore essential. In this research, the objective was to evaluate the genotoxic and cytotoxic effects of AgNP (size range between 2 and 8 nm) on root meristematic cells of Allium cepa (A. cepa). Tests were carried out in the presence of colloidal solution of AgNP and AgNP mixed with carboxymethylcellulose (CMC), using distinct concentrations of AgNP. As a result, when compared to control samples, AgNP induced a mitotic index decrease and an increase of chromosomal aberration number for two studied concentrations. When AgNP was in the presence of CMC, no cytotoxic potential was verified, but only the genotoxic potential for AgNP dispersion having concentration of 12.4 ppm.

Comparison of the effects of various lubricant eye drops on the in vitro rabbit corneal healing and toxicity.

Ingredients of lubricant eye drops are potentially harmful to the ocular surface. The products Optive, Optive Fusion, Neopt were tested regarding corneal irritability versus Vismed Multi and 0.01% benzalkonium chloride as negative and positive control, respectively. Formulas (30-40µl per hour) were applied hourly in-vitro for six days on rabbit corneas (n=5, per product) cultured in artificial anterior chambers (EVEIT system). Initially, four corneal abrasions (2.4-4.6mm2) were induced. All defects were monitored during drop application by fluorescein stains and photographs. To ensure corneal vitality, glucose and lactate concentrations in artificial anterior chamber fluids were determined photometrically. All products showed a complete corneal healing on day 2. Thereafter, all five Optive-treated corneas developed progressive fluorescein-positive epithelial lesions until day six (24.96µm, ±21.45µm, p<0.01). For Optive Fusion three corneas showed corneal erosions on day six (23.11µm, ±37.02µm, p>0.5) while Vismed Multi did not adversely affect the corneal integrity. Glucose/lactate concentrations remained unchanged while lubricants were applied. Histology revealed epithelial loss and severe alterations of the superficial stroma for Optive. Optive Fusion displayed a comparable pathology. Neopt did not significantly affect the corneal healing and integrity. This study suggested a cumulative corneal toxicity of Optive and, to a lesser extent, Optive Fusion most likely caused by its oxidative preservative, SOC. Clinical data are needed to clarify the application frequency at which corneal toxicity might occur. Neopt and Vismed Multi did not affect the corneal integrity.

Dietary Emulsifier-Induced Low-Grade Inflammation Promotes Colon Carcinogenesis.

The increased risks conferred by inflammatory bowel disease (IBD) to the development of colorectal cancer gave rise to the term "colitis-associated cancer" and the concept that inflammation promotes colon tumorigenesis. A condition more common than IBD is low-grade inflammation, which correlates with altered gut microbiota composition and metabolic syndrome, both present in many cases of colorectal cancer. Recent findings suggest that low-grade inflammation in the intestine is promoted by consumption of dietary emulsifiers, a ubiquitous component of processed foods, which alter the composition of gut microbiota. Here, we demonstrate in a preclinical model of colitis-induced colorectal cancer that regular consumption of dietary emulsifiers, carboxymethylcellulose or polysorbate-80, exacerbated tumor development. Enhanced tumor development was associated with an altered microbiota metagenome characterized by elevated levels of lipopolysaccharide and flagellin. We found that emulsifier-induced alterations in the microbiome were necessary and sufficient to drive alterations in major proliferation and apoptosis signaling pathways thought to govern tumor development. Overall, our findings support the concept that perturbations in host-microbiota interactions that cause low-grade gut inflammation can promote colon carcinogenesis. Cancer Res; 77(1); 27-40. ©2016 AACR.

Toxicity study of food-grade carboxymethyl cellulose synthesized from maize husk in Swiss albino mice.

Food-grade carboxymethyl cellulose was prepared from maize husk agro-waste and was evaluated sub-chronic oral toxicity in Swiss albino mice. 40 male mice were divided into 4 groups and fed diets with 0 (control) - 10% CMC for a period of 3 months. Daily oral doses were 5 - 20mg/g body weight to the mice/day. Animal care and handling were conformed according to internationally accepted standard guidelines. Haematological and biochemical parameters were monitored during this period. At the end of the study, tissues and organs were studied for histopathological changes. Repeat-dose oral toxicity study was carried out according to OECD guideline 408. The result did not show any treatment related abnormalities in terms of haematological and biochemical parameters. However, water intake, urine production and urinary sodium excretion increased with increasing doses of CMC. The weekly body weight showed no significant differences between control and mice treated with different doses of CMC. In mice of the treated groups, no abnormalities in the histopathology of liver, heart, lung and kidney were detected. This indicated the prepared CMC has no toxic effect at different doses on cellular structure, and support the safety use of CMC as food additives and an excipient for pharmaceuticals.

Development of mucoadhesive thio-carboxymethyl cellulose for application in buccal delivery of drugs.

AIM: L-cysteine (CYS) was covalently attached to carboxymethyl cellulose (CMC) to obtain the thiolated conjugate CMCCYS. Methodology & results: CMCCYS and controls were investigated in terms of safety, disintegration, erosion and mucoadhesiveness. Furthermore, mechanical, physicochemical properties, mucoadhesive strength, swelling behavior and residence time were evaluated. Exhibiting 99.61 ± 2.51% cell viability, CMCCYS was considered as non toxic at all. Furthermore, CMCCYS displayed 2.8-fold higher polymer stability as well as 5.8-fold less erosion than unmodified CMC. Mucoadhesive strength assay displayed 1.6-fold improved adhesion on buccal mucosa as well as 2.7-fold improved mucoadhesiveness on the rotating cylinder. CONCLUSION: Chemical modification of well-known CMC encourage further evaluation and application of the mucoadhesive potential for the buccal delivery.

Ultrasonic compatibilization of polyelectrolyte complex based on polysaccharides for biomedical applications.

In recent years, there has been an increasing interest in the design of biomaterials for cartilage tissue engineering. This type of materials must meet several requirements. In this study, we apply ultrasound to prepare a compatibilized blend of polyelectrolyte complexes (PEC) based on carboxymethyl cellulose (CMC) and chitosan (CHI), in order to improve stability and mechanical properties through the inter-polymer macroradicals coupling produced by sonochemical reaction. We study the kinetic of the sonochemical degradation of each component in order to optimize the experimental conditions for PEC compatibilization. Scaffolds obtained applying this methodology and scaffolds without ultrasound processing were prepared and their morphology (by scanning electron microscopy), polyelectrolyte interactions (by FTIR), stability and mechanical properties were analyzed. The swelling kinetics was studied and interpreted based on the structural differences between the two kinds of scaffolds. In addition we evaluate the possible in vitro cytotoxicity of the scaffolds using macrophage cells in culture. Our results demonstrate that the ultrasound is a very efficient methodology to compatibilize PEC, exhibiting improved properties compared with the simple mixture of the two polysaccharides. The test with murine macrophage RAW 264.7 cells showed no evince of cytotoxicity, suggesting that PEC biomaterials obtained under ultrasound conditions could be useful in the cartilage tissue engineering field.

The dual effects of carboxymethyl cellulose on the colloidal stability and toxicity of nanoscale zero-valent iron.

Nanoscale zero-valent iron (NZVI) particles are usually modified with surface coating to mitigate the particle stability in water during the environmental application. However, the surface coating may not only influence the particle stabilization but also the particle cytotoxicity. In this study, we investigated the dual effects of carboxymethyl cellulose (CMC) on the colloidal stability and cytotoxicity of NZVI towards gram-negative Escherichia coli (E. coli) and discussed the interrelation between particle stability and cytotoxicity. The effect of CMC concentration, ionic strength (Ca(2+)) and aging treatment on the particle cytotoxicity were also examined. Specifically, the aqueous stability of NZVI suspensions with CMC ratio dose-dependently strengthened within 1 h. The inactivation of E. coli by bare NZVI was significant and concentration- and time-dependent. On the contrary, an increasing reduction in cytotoxicity of NZVI with CMC ratio increasing was observed, even though the particles became more dispersed. TEM analysis demonstrates the membrane disruption and the cellular internalization of nanoparticles after exposure of E. coli to NZVI. However, in the case of CMC-modified NZVI (CNZVI), the bacterial cell wall displays an outer shell of a layer of nanoparticles attached around the outer membrane, but the cell membrane was kept intact. The presence of Ca(2+) can either increase or decrease the cytotoxicity of NZVI and CNZVI, depending on the concentration. The aged NZVI and CNZVI particles did not seem to present obvious bactericidal effect due to the transformation of Fe(0) to the less toxic or non-toxic iron oxides, as indicated by the XRD analysis.