RESUMEN
Surfactant Modified Zeolite (SMZ) represents a versatile, cost-effective permeable reactive material, capable of treating multiple classes of contaminants. The potential for HDTMA-Br, a cationic surfactant commonly used to modify zeolite, to desorb from the zeolite surface has been identified as a potential issue for the ongoing use of SMZ in water remediation contexts. This paper investigates the toxicity of HDTMA-Br towards enteric virus surrogates, F-RNA bacteriophage MS2 and E. coli, Bacillus subtilis, and soil microflora. The concentration of surfactant desorbing from SMZ was quantified through a bioassay using E. coli. Results showed HDTMA-Br concentrations of ≥10-5M were toxic to MS2, ≥10-4M were toxic to E. coli and ≥10-6M were toxic to B. subtilis. No toxic relationship was established between HDTMA-Br and soil microflora. Desorption of ≥10-4M of HDTMA-Br was shown for the two SMZ samples under the mixing conditions used. Effects of this surfactant on total soil microflora were ambiguous since no toxic relationship could be established, however, HDTMA-Br, at concentrations desorbing from SMZ, were shown to impact the soil bacterium B. subtilis. Further research is required to determine the effect of this surfactant on microbial populations and species diversity in soils.
Asunto(s)
Compuestos de Cetrimonio/toxicidad , Tensoactivos/toxicidad , Zeolitas/química , Adsorción , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/crecimiento & desarrollo , Cetrimonio , Compuestos de Cetrimonio/química , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Heces/microbiología , Levivirus/efectos de los fármacos , Levivirus/crecimiento & desarrollo , Microbiología del Suelo , Tensoactivos/químicaRESUMEN
The cationic surfactants carbethoxypendecinium bromide (Septonex) and cetyltrimethylammonium bromide (CTAB) are known to be harmful for certain cell types (bacteria, fungi, mammal cells, etc.). Colloidal complexes of these surfactants with negatively-charged hyaluronic acid (HyA) were prepared for potential drug and/or universal delivery applications. The complexes were tested for their cytotoxic effect on different human cell types - osteoblasts, keratinocytes and fibroblasts. Both the CTAB-HyA and Septonex-HyA complexes were found to reduce the cytotoxicity induced by surfactants alone concerning all the tested concentrations. Moreover, we suggested the limits of HyA protection provided by the surfactant-HyA complexes, e.g. the importance of the amount of HyA applied. We also determined the specific sensitivity of different cell types to surfactant treatment. Keratinocytes were more sensitive to CTAB, while osteoblasts and fibroblasts were more sensitive to Septonex. Moreover, it was indirectly shown that CTAB combines lethal toxicity with cell metabolism induction, while Septonex predominantly causes lethal toxicity concerning fibroblasts. This comprehensive study of the effect of surfactant-HyA complexes on various human cell types revealed that HyA represents a useful CTAB or Septonex cytotoxic effect modulator at diverse levels. Potential applications for these complexes include drug and/or nucleic acid delivery systems, diagnostic dye carriers and cosmetics production.
Asunto(s)
Ácido Hialurónico/química , Tensoactivos/química , Tensoactivos/toxicidad , Recuento de Células , Línea Celular , Cetrimonio , Compuestos de Cetrimonio/química , Compuestos de Cetrimonio/toxicidad , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/toxicidad , Relación Estructura-ActividadRESUMEN
In recent years, we and others have become interested in evaluating the use of surface-enhanced Raman scattering (SERS) tags for early cancer detection and in designing new approaches to demonstrate the applicability of this spectroscopic technique in the clinic. SERS-based imaging in particular offers ultra sensitivity up to the single molecule, multiplexing capability, and increased photostability and has been shown to outperform fluorescence. However, to employ SERS tags for early cancer detection, it is important to understand their interaction with cells and determine their cytotoxicity. We have been particularly interested for quite some time in determining if and how gold nanostars, which have been demonstrated as outstanding SERS enhancing substrates, can be safely employed in living systems and translated to the clinic. In this study, we carried out a multiparametric in vitro study to look at the cytotoxicity and cellular uptake of gold nanoparticles on human glioblastoma and human dermal fibroblast cell lines. Cytotoxicity was evaluated by incubating cells with three different morphologies of AuNPs, namely nanospheres, nanorods, and nanostars, each having three different surface chemistries (cetyltrimethylammonium bromide (CTAB), poly(ethylene glycol) (PEG), and human serum albumin (HSA)). Our results showed that the surface chemistry of the nanoparticles had predominant effects on cytotoxicity, and the morphology and size of the nanoparticles only slightly affected cell viability. CTAB-coated particles were found to be the most toxic to cells, and PEGylated nanostars were determined to be the least toxic. Caspase-3 assay and LDH assay revealed that cell death occurs via apoptosis for cancerous cells and via necrosis for healthy ones. Cellular uptake studies carried out via TEM showed that the particles retain their shape even at long incubation times, which may be beneficial for in vivo SERS-based disease detection. Overall, this study provides valuable information on gold-nanoparticle-induced cytotoxicity that can be leveraged for the development of safe and effective nanoparticle-based therapeutic and diagnostic systems.
Asunto(s)
Supervivencia Celular/efectos de los fármacos , Oro/toxicidad , Nanopartículas del Metal/toxicidad , Caspasa 3/metabolismo , Línea Celular Tumoral , Células Cultivadas , Cetrimonio , Compuestos de Cetrimonio/química , Compuestos de Cetrimonio/toxicidad , Oro/química , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Polietilenglicoles/química , Polietilenglicoles/toxicidad , Albúmina Sérica/química , Albúmina Sérica/toxicidad , Espectrometría Raman/métodos , Propiedades de SuperficieRESUMEN
Aptamer-conjugated gold nanorods (AuNRs) are excellent candidates for targeted hyperthermia therapy of cancer cells. However, in high concentrations of AuNRs, aptamer conjugation alone fails to result in highly cell-specific AuNRs due to the presence of positively charged cetyltrimethylammonium bromide (CTAB) as a templating surfactant. Besides causing nonspecific electrostatic interactions with the cell surfaces, CTAB can also be cytotoxic, leading to uncontrolled cell death. To avoid the nonspecific interactions and cytotoxicity triggered by CTAB, we report the further biologically inspired modification of aptamer-conjugated AuNRs with bovine serum albumin (BSA) protein. Following this modification, interaction between CTAB and the cell surface was efficiently blocked, thereby dramatically reducing the side effects of CTAB. This approach may provide a general and simple method to avoid one of the most serious issues in biomedical applications of nanomaterials: nonspecific binding of the nanomaterials with biological cells.
Asunto(s)
Aptámeros de Nucleótidos/toxicidad , Compuestos de Cetrimonio/toxicidad , Oro/toxicidad , Nanotubos/toxicidad , Albúmina Sérica Bovina/química , Animales , Aptámeros de Nucleótidos/química , Bovinos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cetrimonio , Compuestos de Cetrimonio/química , Oro/química , Humanos , Ácidos Nucleicos Inmovilizados , Nanotubos/química , Unión ProteicaRESUMEN
This report compares the effect of lipid and polymeric nanoparticles upon human neutrophils in the presence of cationic surfactants. Nanostructured lipid carriers and poly(lactic-co-glycolic) acid nanoparticles were manufactured as lipid and polymeric systems, respectively. Some cytotoxic and proinflammatory mediators such as lactate dehydrogenase (LDH), elastase, O2(â¢-), and intracellular Ca(2+) were examined. The nanoparticles showed a size of 170-225 nm. Incorporation of cetyltrimethylammonium bromide or soyaethyl morpholinium ethosulfate, the cationic surfactant, converted zeta potential from a negative to a positive charge. Nanoparticles without cationic surfactants revealed a negligible change on immune and inflammatory responses. Cationic surfactants in both nanoparticulate and free forms induced cell death and the release of mediators. Lipid nanoparticles generally demonstrated a greater response compared to polymeric nanoparticles. The neutrophil morphology observed by electron microscopy confirmed this trend. Cetyltrimethylammonium bromide as the coating material showed more significant activation of neutrophils than soyaethyl morpholinium ethosulfate. Confocal microscope imaging displayed a limited internalization of nanoparticles into neutrophils. It is proposed that cationic nanoparticles interact with the cell membrane, triggering membrane disruption and the following Ca(2+) influx. The elevation of intracellular Ca(2+) induces degranulation and oxidative stress. The consequence of these effects is cytotoxicity and cell death. Caution should be taken when selecting feasible nanoparticulate formulations and cationic additives for consideration of applicability and toxicity.
Asunto(s)
Lípidos , Nanopartículas , Neutrófilos/efectos de los fármacos , Polímeros , Cationes , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cetrimonio , Compuestos de Cetrimonio/química , Compuestos de Cetrimonio/toxicidad , Humanos , Lípidos/química , Lípidos/toxicidad , Nanopartículas/química , Nanopartículas/toxicidad , Tamaño de la Partícula , Polímeros/química , Polímeros/toxicidadRESUMEN
BACKGROUND: The liver is the most frequent organ for placement of hydatid cyst disease. All known protoscolicidals that are used for echinococcus degeneration have a risk of caustic secondary sclerosing cholangitis. The cetrimide-chlorhexidine combination is an effective protoscolicidal agent for treatment of hydatid liver cysts. OBJECTIVES: The aim of this experimental study was to examine this combination for potential risks of caustic secondary sclerosing cholangitis. MATERIAL AND METHODS: Thirty rats were enrolled and divided into two groups. In the study group, 0.15 mL of a cetrimide (0.5%) and chlorhexidine (0.05%) combination was injected into the bile ducts for five minutes. The control group included the same amount of normal saline and waiting period. The rats were followed for 120 days and the living rats were examined for biliary injury by biochemical analysis and histopathology. RESULTS: No specific histopathological findings for caustic sclerosing cholangitis such as bile duct stricture or periductal fibrosis were present in any groups. Other pathological criteria demonstrating inflammation including portal inflammation, bile duct proliferation and necrosis were similar in both groups. Biochemical analysis including a liver function test (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase) appeared similar to the control group. CONCLUSIONS: A cetrimide 0.5% and chlorhexidine 0.05% combination has similar liver function results and histopathological effects to normal saline on bile ducts and it appears to be safe for bile ducts.
Asunto(s)
Antiinfecciosos/toxicidad , Conductos Biliares/efectos de los fármacos , Compuestos de Cetrimonio/toxicidad , Clorhexidina/toxicidad , Colangitis Esclerosante/inducido químicamente , Animales , Conductos Biliares/patología , Proliferación Celular/efectos de los fármacos , Cetrimonio , Colangitis Esclerosante/patología , Combinación de Medicamentos , Femenino , Pruebas de Función Hepática , Necrosis , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
The removal of nutrients by algae is regarded as a vital process in wastewater treatment, however algal cell activity can be inhibited by some toxic chemicals during the biological process. This study investigated the uptake of ammonia nitrogen (NH4âº) and total phosphorus (TP) by a green alga (Chlorella vulgaris) and algal cell responses under the stress of cetyltrimethyl ammonium bromide (CTAB), a representative for quaternary ammonium compounds (QACs, cationic surfactants). When the concentration of CTAB increased from 0 to 0.6 mg/L, the uptake efficiencies of NH4⺠and TP decreased from 88% to 18% and from 96% to 15%, respectively. Algal cell responses showed a decline in photosynthesis activity as indicated by the increase of chlorophyll autofluorescence from 2.9 a.u. to 25.3 a.u.; and a decrease of cell viability from 88% to 51%; and also a drop in esterase activity as indicated by the decrease in fluorescence of fluorescein diacetate stained cells from 71.5 a.u. to 4.7 a.u. Additionally, a transcription and translation response was confirmed by an enhancement of PO peak and amide II peak in algal cellular macromolecular composition stimulated by CTAB. The results suggest that QACs in wastewater may inhibit nutrient uptake by algae significantly through declining algal cell activities.
Asunto(s)
Compuestos de Cetrimonio/toxicidad , Chlorella vulgaris/efectos de los fármacos , Chlorella vulgaris/metabolismo , Eliminación de Residuos Líquidos/métodos , Purificación del Agua/métodos , Análisis de Varianza , Transporte Biológico/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cetrimonio , Chlorella vulgaris/fisiología , Clorofila/metabolismo , Esterasas/metabolismo , Fluorescencia , Fósforo/farmacocinética , Fotosíntesis/efectos de los fármacos , Fotosíntesis/fisiología , Compuestos de Amonio Cuaternario/farmacocinéticaRESUMEN
Sodium dodecyl benzene sulfonate (SDBS) and cetyl trimethyl ammonium chloride (CTAC) are two kinds of surfactants widely applied in various industries. The tremendous direct discharge of these surfactants into natural waters has posed a significant threat to ecosystems. Dunaliella bardawil was employed in the present research to test the toxic effects of SDBS, CTAC, and their mixture on cell growth, cellular morphology, ß-carotene accumulation, and enzymatic activities of superoxide dismutase (SOD) and catalase (CAT). The results showed that SDBS at 200, 550, 900, 1,350, 1,800, and 2,400 mg/L and CTAC at 0.4, 0.7, 1.0, 1.3, 2.8, and 3.5 mg/L inhibited algal growth and ß-carotene accumulation, both of which declined and then increased. In particular, CTAC (median inhibitory concentration at 10 days [IC50](10 d) = 2.8 ± 1.49 mg/L) was more hazardous than SDBS (IC50(10 d) = 2,044 ± 637.3 mg/L). The additive index (AI) calculated from carotene content data was (-4.10, -1.67) < 0, indicating an antagonistic effect between SDBS and CTAC. Algae cultivated at level 6 of the binary system showed hormesis due to the mitigated toxicity; SDBS at 2,400 mg/L, CTAC at 3.5 mg/L, and combined surfactants at level 6 exerted lethal effects on D. bardawil. Both SOD and CAT activities showed similar associations with varied concentrations of surfactants: SOD was significantly promoted by 550 to 1,800 mg/L SDBS, 0.7 to 1.3 mg/L CTAC, and mixtures at levels 2 to 4; CAT was clearly promoted by 900 mg/L SDBS, 0.4 to 1.3 mg/L CTAC, and mixtures at levels 2 to 4.
Asunto(s)
Bencenosulfonatos/toxicidad , Compuestos de Cetrimonio/toxicidad , Chlorophyta/efectos de los fármacos , Tensoactivos/toxicidad , Carotenoides/metabolismo , Catalasa/metabolismo , Cetrimonio , Oxidación-Reducción , Superóxido Dismutasa/metabolismo , Contaminantes Químicos del Agua/toxicidad , beta Caroteno/metabolismoRESUMEN
The objective of this study was the preparation, physico-chemical characterization and statistical optimization of cationic solid lipid nanoparticles (SLN) prepared by the PIT method as potential carrier for gene therapy, emphasizing the application of factorial design in such a kind of studies. The preliminary screening from a physico-chemical point of view on three cationic lipids (CTAB, DDAB and DOTAP), selected on the basis of their different chemical structure and increasing lipophilicity, allowed us to select SLN with DOTAP, due to its higher zeta potential and smaller particle size. Afterward, a 2(2) full factorial experimental design was developed in order to study the effects of two independent variables (amount of DOTAP and concentration of lipid matrix) and their interaction on mean particle size and zeta potential values. The factorial planning was validated by ANOVA analysis; the correspondence between the predicted values of size and zeta and those measured experimentally confirmed the validity of the design and the equation applied for its resolution. The factorial design showed a significant influence of the independent variables on the selected parameters; in particular, a higher effect of DOTAP was observed on zeta potential value. Different dilutions of the optimized SLN containing 7% w/w of cutina CP and 1% w/w of DOTAP, with size and zeta potential values respectively of 462.9 nm and 50.8 mV, were in vitro examined to evaluate the possible cytotoxicity on two models of cell cultures: human prostate cancer androgen-non-responsive DU-145 cells and primary cultures of rat astrocytes.
Asunto(s)
Portadores de Fármacos/química , Lípidos/química , Nanopartículas/química , Nanotecnología/métodos , Animales , Astrocitos/efectos de los fármacos , Cationes/química , Cationes/toxicidad , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cetrimonio , Compuestos de Cetrimonio/química , Compuestos de Cetrimonio/toxicidad , Portadores de Fármacos/toxicidad , Ácidos Grasos Monoinsaturados/química , Ácidos Grasos Monoinsaturados/toxicidad , Humanos , Lípidos/toxicidad , Modelos Estadísticos , Nanopartículas/toxicidad , Nanopartículas/ultraestructura , Palmitatos/química , Palmitatos/toxicidad , Tamaño de la Partícula , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/toxicidad , RatasRESUMEN
Gold nanorods (Au-NRs) have attracted enormous interest due to their size and unique optical properties. Many studies have demonstrated their use in biomedical systems. However, their potential toxicity is not fully understood. This study evaluated the effects of the Au-NRs (15 nM × 64 nM) coated with CTAB (cetyltrimethylammonium bromide) or PEG (polyethylene glycol) in human erythrocytes on the induction of haemolysis and erythroptosis. In our study, erythroptosis (also known as eryptosis) was determined systematically through the measurement of feature events of apoptosis by flow cytometry. We found that the CTAB- and PEG-coated Au-NRs up to 0.5 nM did not cause severe haemolysis. However, the CTAB-Au-NRs were more toxic than the PEG-Au-NRs. The toxicity of the CTAB-Au-NRs was largely due to the CTAB residues from desorption or incomplete purification. Mechanistically, cytosolic Ca(2+) ions seem to be the key mediator in the eryptosis/erythroptosis mediated by the CTAB or CTAB-Au-NRs while caspase-3 and reactive oxygen species did not contribute much to the process.
Asunto(s)
Apoptosis/efectos de los fármacos , Compuestos de Cetrimonio/toxicidad , Eritrocitos/efectos de los fármacos , Oro/química , Nanotubos/toxicidad , Polietilenglicoles/toxicidad , Caspasa 3/metabolismo , Cetrimonio , Eritrocitos/enzimología , Hemólisis/efectos de los fármacos , Humanos , Técnicas In Vitro , Estrés Oxidativo/efectos de los fármacosRESUMEN
Quaternary ammonium compounds (QAC) constitute a family of widely used chemical substances. The QAC benzalkonium chloride (BAC) has caused bronchoconstriction in human beings by poorly understood mechanisms and lung damage at high concentration as shown in a single rat study. This study evaluates acute airway effects in mice after inhalation of aerosols of the QACs, BAC, hexadecyl trimethyl ammonium bromide (HTA), cetyl pyridinium chloride (CPC) and dimethyl dioctadecyl ammonium bromide (DDA). The QACs gave rise to concentration-dependent decreases in the tidal volume (VT) and a concomitant increase in respiratory rate indicating pulmonary irritation. The potencies of the QAC to induce these effects were in the order: BAC > HTA = CPC > DDA. Furthermore, inhalation of BAC and CPC aerosols gave rise to pulmonary inflammation as apparent from bronchoalveolar lavage. Stimulation of nasal trigeminal nerve endings by QAC, which may serve as a warning signal, was absent.
Asunto(s)
Pulmón/efectos de los fármacos , Neumonía/inducido químicamente , Compuestos de Amonio Cuaternario/toxicidad , Aerosoles , Animales , Compuestos de Benzalconio/toxicidad , Lavado Broncoalveolar , Líquido del Lavado Bronquioalveolar/inmunología , Cetrimonio , Compuestos de Cetrimonio/toxicidad , Cetilpiridinio/toxicidad , Relación Dosis-Respuesta a Droga , Femenino , Exposición por Inhalación , Pulmón/inmunología , Pulmón/fisiopatología , Ratones , Ratones Endogámicos BALB C , Neumonía/inmunología , Neumonía/fisiopatología , Frecuencia Respiratoria/efectos de los fármacos , Volumen de Ventilación Pulmonar/efectos de los fármacos , Factores de TiempoRESUMEN
The joint action of binary mixtures of cetyltrimethyl ammonium chloride (CTAC), a cationic surfactant, and six aromatic hydrocarbons (AHs) on green algae Chlorella vulgaris was investigated. In single systems, inhibition efficiency of CTAC on the growth of algae was much higher than that of AHs (benzene, toluene, phenol, nitrobenzene, phenanthrene and fluoranthene). In combined systems, the toxicity of CTAC was enhanced by low concentrations of AHs. 96 h EC(50) value of CTAC varied from 145±13.35-56±8.27 to 56±8.27-226±8.22 µg/L when exposed to 0-1.13 and 1.13-100.84 µg/L fluoranthene, respectively. Zeta potential of algae initially increased and then decreased with the increase of fluoranthene concentration, whereas residual CTAC concentration displayed an opposite trend in the combined system. These results of this investigation showed that fluoranthene influenced the sorption of CTAC by C. vulgaris. The above results indicated that cationic surfactants and AHs have synergetic toxic effects on aquatic biota.
Asunto(s)
Compuestos de Cetrimonio/toxicidad , Chlorella vulgaris/efectos de los fármacos , Hidrocarburos Aromáticos/toxicidad , Tensoactivos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Cetrimonio , Compuestos de Cetrimonio/química , Chlorella vulgaris/crecimiento & desarrollo , Hidrocarburos Aromáticos/química , Estructura Molecular , Tensoactivos/química , Pruebas de Toxicidad , Contaminantes Químicos del Agua/químicaRESUMEN
The toxic interaction of the azo dye-chrysoidine hydrochloride combined with cetyltrimethyl ammonium bromide (CTMAB) in living tissue was studied in vitro. The absorption spectrum, resonance light scattering (RLS), circular dichroism (CD) and transmission electron microscopy (TEM) results showed that the toxicity of chrysoidine hydrochloride itself to calf thymus DNA (ct-DNA) is weak, while the chrysoidine hydrochloride-CTMAB combined pollution showed obvious toxic interaction with ct-DNA. The chrysoidine hydrochloride-CTMAB combined contamination can interact with ct-DNA to form an ion-associated complex through electrostatic and hydrophobic forces. The conformation of DNA was changed in the interaction process to show toxic. The experimental results showed that the combination of chrysoidine hydrochloride-CTMAB has higher toxicity to ct-DNA than either chrysoidine hydrochloride or CTMAB individually, and the combined pollution showed a strong toxic co-effect at a dose of 3.0x10(-4) mol L(-1) chrysoidine hydrochloride and 1.6x10(-5) mol L(-1) CTMAB.
Asunto(s)
Compuestos de Cetrimonio , ADN , p-Aminoazobenceno/análogos & derivados , Animales , Antiinfecciosos Locales/química , Antiinfecciosos Locales/toxicidad , Bovinos , Cetrimonio , Compuestos de Cetrimonio/química , Compuestos de Cetrimonio/toxicidad , Dicroismo Circular , ADN/química , ADN/efectos de los fármacos , Contaminantes Ambientales/química , Contaminantes Ambientales/toxicidad , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Transmisión , Conformación de Ácido Nucleico , p-Aminoazobenceno/química , p-Aminoazobenceno/toxicidadRESUMEN
PURPOSE: The use of preservatives such as benzalkonium chloride (BAC) usually increases the toxicity of pharmaceutical tear substitutes. HP-guar has been recently introduced as a new artificial tear substitute and includes the preservative Polyquad (0.001%), which is considered to be non-toxic. We therefore examined the effect of preserved (cetrimide 0.01%) and unpreserved HPMC (hydroxypropylmethyl cellulose) and HP-guar in dose and time-response experiments in a human corneal and conjunctival epithelial cell culture model. METHODS: Immortalized human conjunctival and corneal epithelial cells were cultured in 96-well plates at 37 degrees C with 5% CO(2) and exposed to the test solutions. The ATP content was quantified by means of a luminescence-based ATP assay, intracellular esterase activity by double fluorescent viability staining (calcein AM/ethidium homodimer D-1) and cell migration by a colony dispersion assay. All experiments were performed in triplicate and repeated at least once. The significance of differences was determined with an unpaired two-sided t-test. RESULTS: HPMC with preservative severely reduced the ATP content at all concentrations tested. Unpreserved HPMC, however, showed an inhibition of ATP production only at 100% and good esterase activity. HP-guar with and without preservative were found to reduce ATP activity more than unpreserved HPMC, but the unpreserved solution was found to reduce cellular ATP levels significantly more than the preserved solution. CONCLUSIONS: The new preservative Polyquad induced significantly less cytotoxicity than cetrimide. However, even unpreserved HP-guar can induce cytotoxicity in vitro, while unpreserved HPMC remains a good alternative tear substitute with low cytotoxicity.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Compuestos de Cetrimonio/toxicidad , Conjuntiva/efectos de los fármacos , Soluciones para Lentes de Contacto/toxicidad , Células Epiteliales/efectos de los fármacos , Epitelio Corneal/efectos de los fármacos , Metilcelulosa/análogos & derivados , Soluciones Oftálmicas/toxicidad , Polímeros/toxicidad , Polisacáridos/toxicidad , Conservadores Farmacéuticos/toxicidad , Adenosina Trifosfato/metabolismo , Células Cultivadas , Cetrimonio , Relación Dosis-Respuesta a Droga , Esterasas/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Derivados de la Hipromelosa , Técnicas In Vitro , Metilcelulosa/toxicidad , Concentración OsmolarRESUMEN
Eight widely used surfactants (cetyltrimethylammonium bromide; CTAB, benzethonium chloride; Hyamine 1622, 4-nonylphenol; NP, octylphenol ethoxylate; Triton X-100, dodecylbenzene sulfonate; LAS, lauryl sulfate; SDS, pentadecafluorooctanoic acid; PFOA, and perfluorooctane sulfonate; PFOS) were selected to examine their acute toxicities and effects on oxidative stress and cholinesterase (ChE) activities in Dugesia japonica. The differences in acute toxicity among eight surfactants to planarians were at least in the range of three orders of magnitudes. The toxicity rank of surfactants according to estimated 48-h LC(50) was SDS>NP>LAS>Hyamine 1622>CTAB>Triton X-100>PFOS>PFOA. The toxicity rank of surfactants according to 96-h LC(50) was as follows: SDS>CTAB>NP>LAS>Hyamine 1622>Triton X-100>PFOS>PFOA. There were significant increases in catalase activities in planarians exposed to LAS at nominal concentrations of 0.5 or 1 mgl(-1) and to PFOS at nominal concentrations of 5 or 10 mgl(-1) after 48-h exposure. Inhibitions of ChE activities were found in planarians exposed to Hyamine 1622 at all concentrations tested, to PFOS at nominal concentration of 10 mgl(-1), to PFOA at nominal concentrations of 50 or 100 mgl(-1) and to NP at nominal concentration of 0.5 mgl(-1). A significant increase in ChE activities was also observed in planarian exposed to Triton X-100 at nominal concentration of 5 mgl(-1). The implication of ChE inhibition by NP, PFOS and PFOA on neurological and behavioral effects in aquatic animals requires further investigation.
Asunto(s)
Colinesterasas/metabolismo , Estrés Oxidativo , Planarias/efectos de los fármacos , Tensoactivos/toxicidad , Animales , Bencetonio/toxicidad , Caprilatos/toxicidad , Catalasa/metabolismo , Cetrimonio , Compuestos de Cetrimonio/toxicidad , Fluorocarburos/toxicidad , Dosificación Letal Mediana , Peroxidación de Lípido/efectos de los fármacos , Nivel sin Efectos Adversos Observados , Fenoles/toxicidad , Planarias/metabolismo , Proteínas/metabolismo , Ácidos Sulfónicos/toxicidad , Superóxido Dismutasa/metabolismoRESUMEN
Gold nanorods prepared in hexadecyltrimethylammonium bromide (CTAB) solution are expected to provide novel materials for photothermal therapy and photo-controlled drug delivery systems. Since gold nanorods stabilized with CTAB show strong cytotoxicity, we developed a technique to modify these with polyethyleneglycol (PEG) for medical applications. PEG-modification was achieved by adding mPEG-SH in the CTAB solution, then, excess CTAB was removed by dialysis. PEG-modified gold nanoparticles showed a nearly neutral surface, and had little cytotoxicity in vitro. Following intravenous injection into mice, 54% of injected PEG-modified gold nanoparticles were found in blood at 0.5 h after intravenous injection, whereas most of gold was detected in the liver in the case of original gold nanorods stabilized with CTAB.
Asunto(s)
Oro/administración & dosificación , Nanoestructuras , Polietilenglicoles/administración & dosificación , Animales , Supervivencia Celular/efectos de los fármacos , Cetrimonio , Compuestos de Cetrimonio/toxicidad , Oro/farmacocinética , Oro/toxicidad , Células HeLa , Humanos , Masculino , Ratones , Distribución TisularRESUMEN
The objectives of this work were (i) to prepare physically stable cationic microparticles and (ii) to study the impact of the surface properties on microparticle phagocytosis and the phenotype of dendritic cells (DC). Protein loaded biodegradable microparticles from poly(lactic-co-glycolic acid) [PLGA] were produced in a micromixer-based w/o/w solvent evaporation procedure. Anionic particles were obtained by using polyvinyl alcohol (PVA) as stabilizing agent; for cationic surfaces cetyltrimethylammonium bromide (CTAB) and chitosan/PVA or DEAE-dextran/PVA blends were evaluated. In phagocytosis studies human monocytes and monocyte-derived DC were incubated with microparticles and analysed by flow cytometry. While CTAB modified microparticles lost their positive charge and aggregated due to CTAB desorption from the particle surface, the modification with chitosan and DEAE-dextran resulted in stable microparticles without cell toxicity. Due to a very low endotoxin content, phagocytosis of anionic and cationic microparticles did not induce an upregulation of maturation-associated surface markers on DC. DEAE-dextran modified microparticles showed an enhanced model protein delivery into phagocytic cells. Overall, PLGA microparticles are suitable vehicles for protein delivery to DC, which might be used for DC-based cell therapies.
Asunto(s)
Antígenos/administración & dosificación , Células Dendríticas/metabolismo , Sistemas de Liberación de Medicamentos , Ácido Láctico/administración & dosificación , Ácido Poliglicólico/administración & dosificación , Polímeros/administración & dosificación , Antígenos/metabolismo , Antígenos CD/análisis , Células Cultivadas , Cetrimonio , Compuestos de Cetrimonio/química , Compuestos de Cetrimonio/toxicidad , Quitosano/administración & dosificación , DEAE Dextrano/administración & dosificación , Células Dendríticas/inmunología , Excipientes , Humanos , Inmunoglobulinas/análisis , Glicoproteínas de Membrana/análisis , Tamaño de la Partícula , Fagocitosis , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Propiedades de Superficie , Antígeno CD83RESUMEN
The continuous discharge of pharmaceuticals and personal care products into the environment results in a chronic exposure of aquatic organisms to these substances and their metabolites. As concentrations in surface waters are in the ng/L range, and sometimes in the low microg/L range, they are not likely to result in lethal toxicity. However, prolonged exposure to low concentrations of anthropogenic chemicals may lead to sublethal effects, including changes in behaviour. The aim of this study was to assess the effect of three pharmaceuticals, the antidepressant fluoxetine, the analgesic ibuprofen and the anti-epileptic carbamazepine, and one cationic surfactant, cetyltrimethylammonium bromide (CTAB), on the activity of the benthic invertebrate Gammarus pulex (Crustacea: Amphipoda: Gammaridae). We used the multispecies freshwater biomonitor to assess changes in activity of G. pulex in a quantitative manner. Exposure to low concentrations (10-100ng/L) of fluoxetine and ibuprofen resulted in a significant decrease in activity, whereas the activity of G. pulex at higher concentrations (1microg/L-1mg/L) was similar to the control. Response to carbamazepine showed a similar pattern, however, differences were not significant. The tested surfactant CTAB evoked a decrease in activity at increasing concentration. These behavioural effect concentrations were 10(4) to 10(7) times lower than previously reported LOECs and in the range of environmentally occurring concentrations. The potential consequences of this decreased activity for G. pulex population growth and benthic community structure and the exposure to mixtures of pharmaceuticals deserves further attention.
Asunto(s)
Anfípodos/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Analgésicos no Narcóticos/toxicidad , Animales , Anticonvulsivantes/toxicidad , Antidepresivos de Segunda Generación/toxicidad , Carbamazepina/toxicidad , Cetrimonio , Compuestos de Cetrimonio/toxicidad , Relación Dosis-Respuesta a Droga , Monitoreo del Ambiente , Fluoxetina/toxicidad , Agua Dulce , Ibuprofeno/toxicidad , Dosificación Letal Mediana , Actividad Motora/efectos de los fármacos , Tensoactivos/toxicidadRESUMEN
Previously, we have reported a novel nanoparticle-based DNA vaccine delivery system, which elicited strong immune responses against antigens of interest encoded by the DNA. The nanoparticles were engineered by cooling pre-formed warm microemulsions comprised of emulsifying wax as the oil phase and hexadecyltrimethyl ammonium bromide (CTAB) as the surfactant. However, the poor aqueous stability of the nanoparticles and the emulsifying wax in the nanoparticles may severely limit the applications of the nanoparticles. In the present study, we used lecithin, a more biocompatible material, instead of emulsifying wax, to prepared lecithin-based cationic nanoparticles. The 50% growth inhibition concentration (IC(50)) of the lecithin-based nanoparticles was found to be more than 1,000-fold higher than that of the emulsifying wax-based nanoparticles. Moreover, the stability of the lecithin nanoparticles was also significantly increased. The size of the nanoparticles did not significantly change during a 6-month storage period at room temperature. Finally, when plasmid DNA was adsorbed on their surface, the lecithin nanoparticles successfully transfected cells in culture. These lecithin-based nanoparticles may hold great potentials as a DNA (vaccine) delivery system.
Asunto(s)
ADN/metabolismo , Técnicas de Transferencia de Gen , Nanoestructuras , Fosfatidilcolinas/química , Animales , Cationes , Línea Celular , Proliferación Celular , Cetrimonio , Compuestos de Cetrimonio/química , Compuestos de Cetrimonio/toxicidad , ADN/genética , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Ratones , Fosfatidilcolinas/metabolismo , Fosfatidilcolinas/toxicidad , Propiedades de Superficie , Tensoactivos/química , Tensoactivos/toxicidad , TransfecciónRESUMEN
Hexadecyltrimethylammonium bromide (CTAB), which is necessary for the preparation of gold nanorods (NRs), was extracted from a NR solution into a chloroform phase containing phosphatidylcholine (PC). After three extractions, the zeta potential of the NRs remained positive, but its magnitude decreased from +67 +/- 1 to +15 +/- 1 mV. Transmission electron microscopy and energy-dispersive X-ray analysis indicated that the NRs were passivated with PC. The PC layer on the NR surface contributed to the prevention of NR aggregation. The PC-passivated NRs showed low cytotoxicity in comparison with twice-centrifuged NRs. It was shown that a negligible amount of CTAB was dispersed in the NR solution after the extraction. The extraction using a chloroform phase containing PC was found to be a convenient way of replacing the CTAB with alternative capping agents such as PC. This is a key technique for preparing functional NRs that can have practical applications.