RESUMEN
There is a pressing need to find reliable biomarkers for the early diagnosis of silica-induced nephropathy. Abundant genes are upregulated in damaged kidneys with subsequent protein products appearing in the urine. Liver-type fatty acid-binding protein (L-FABP) and kidney injury molecule-1 (KIM-1) are among the most promising. Our objective was to study the importance of L-FABP and KIM-1 genes and their urinary proteins in the early detection of silica-induced renal injury, as compared with other conventional biomarkers. A cross-sectional study was conducted among 90 pottery workers occupationally exposed to silica, as compared to 90 controls. A full history taking and complete clinical examination were performed. Levels of serum creatinine, liver enzymes, urinary silicon, KIM-1, and L-FABP gene expression and protein products were measured. Estimated glomerular filtration rate (eGFR) was calculated, and abdominal ultrasound was performed. The results showed that the silica-exposed group had a statistically significant increase in serum creatinine and urinary silica, as well as a significant decrease in eGFR. Additionally, a significant increase in KIM-1 and L-FABP gene expression, associated with a significant increase in their urinary protein, was found among the exposed group. A positive correlation between urinary silica level and L-FABP gene expression was also found. A receiver operating characteristic curve analysis for L-FABP and KIM-1 gene as predictors for silica-induced nephropathy showed that L-FABP gene and protein specificity were greater than the KIM-1 gene and protein. Taken together, these findings suggest that the L-FABP gene and its protein product may be used as early indicators for renal injury among silica exposed workers.
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Proteínas de Unión a Ácidos Grasos/genética , Receptor Celular 1 del Virus de la Hepatitis A/genética , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/genética , Dióxido de Silicio/sangre , Adulto , Biomarcadores , Estudios de Casos y Controles , Creatinina/sangre , Egipto , Femenino , Expresión Génica , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/orina , Dióxido de Silicio/efectos adversos , Dióxido de Silicio/orina , Adulto JovenRESUMEN
Organic and inorganic antigens were studied simultaneously in the same cohort of sarcoidosis patients to investigate whether correlations between clinical characteristics and immunological sensitization could reveal new phenotypes. Sensitization to antigens of mycobacteria, Propionibacterium acnes catalase and vimentin was investigated in 201 sarcoidosis and 51 obstructive sleep apnoea patients, serving as control group. Sensitization to aluminium, beryllium, silica and zirconium was also studied in 105 of the sarcoidosis patients and in 24 of the controls. A significantly higher percentage of sarcoidosis patients (27·6%) than controls (4·2%) had an immunological response to metals or silica (P = 0·014). A higher percentage of these sarcoidosis patients showed fibrosis on chest X-ray 5 years after the diagnosis (69·2 versus 30·3%, P = 0·016). No significant differences in mycobacterial or vimentin enzyme-linked immunospot (ELISPOT) assay results were observed between sarcoidosis and control patients. A significantly lower percentage of sarcoidosis patients (3·5%) than control patients (15·7%) had a positive ELISPOT for P. acnes catalase (P = 0·003). However, sarcoidosis patients sensitized to P. acnes catalase were more likely to have skin involvement, while sarcoidosis patients sensitized to mycobacterial antigens were more likely to have cardiac involvement. Our study suggests a more prominent role for inorganic triggers in sarcoidosis pathogenesis than previously thought. Immunological sensitization to inorganic antigens was associated with development of fibrotic sarcoidosis. No association was found between sensitization to bacterial antigens or vimentin and sarcoidosis in Dutch patients. However, our data suggest that trigger-related phenotypes can exist in the heterogeneous population of sarcoidosis patients.
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Aluminio/inmunología , Antígenos/inmunología , Berilio/inmunología , Sarcoidosis/inmunología , Dióxido de Silicio/inmunología , Circonio/inmunología , Adulto , Aluminio/sangre , Antígenos/sangre , Proteínas Bacterianas/sangre , Proteínas Bacterianas/inmunología , Berilio/sangre , Catalasa/sangre , Catalasa/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Propionibacterium acnes/inmunología , Propionibacterium acnes/metabolismo , Sarcoidosis/sangre , Dióxido de Silicio/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/inmunología , Vimentina/sangre , Vimentina/inmunología , Circonio/sangreRESUMEN
Avobenzone (AVO), oxybenzone (OXY), and octyl methoxycinnamate (OMC), are widely used UV filters. The aim of this study was to investigate the effect of incorporation in mesoporous silica (SBA-15) on their cutaneous deposition and permeation. Stick formulations containing "free" and "incorporated" UV filters (SF1 and SF2, respectively) were prepared and characterized with respect to their physicochemical, thermal, and functional properties. Cutaneous delivery experiments using porcine skin with quantification by UHPLC-MS/MS, demonstrated that skin deposition of AVO and OXY after application of SF2 for 6 and 12â¯h was significantly lower than that from SF1 at each time-point (Student t-test, pâ¯<â¯0.05): e.g. OXY permeation across the skin was 30-, 12- and 1.5-fold lower after 6, 12 and 24â¯h, respectively, following application of SF2. Cutaneous biodistribution profiles of AVO and OXY to 800⯵m evidenced a significant decrease in the amounts in the viable epidermis and dermis. In contrast, deposition of the more lipophilic OMC was not significantly different (pâ¯Ëâ¯0.05). In vitro photoprotective efficacy results demonstrated that adsorption/entrapment of UV filters enhanced the sun protection factor by 94%. In conclusion, SBA-15, an innovative mesoporous material, increased photoprotection by UV filters while reducing their cutaneous penetration and transdermal permeation.
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Dermis/metabolismo , Epidermis/metabolismo , Dióxido de Silicio/sangre , Absorción Cutánea/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Administración Cutánea , Animales , Benzofenonas/química , Cromatografía Líquida de Alta Presión/métodos , Cinamatos/química , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Estabilidad de Medicamentos , Propiofenonas/química , Dióxido de Silicio/química , Factor de Protección Solar/métodos , Protectores Solares/administración & dosificación , Protectores Solares/química , Porcinos , Espectrometría de Masas en Tándem/métodos , Distribución Tisular/fisiologíaRESUMEN
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune systemic disease characterized by diffuse fibrosis of skin and visceral organs due to different genetic, infectious, and/or environmental/occupational causative factors, including the inhalation of silica dust. OBJECTIVES: To investigate serum trace elements including silicon (s-Si) levels in SSc patients living in a restricted geographical area with high density of worksites with silica exposure hazard. METHODS: This case-control study included 80 SSc patients (M:F 10:70; aged 58.4⯱â¯11.9SD years, mean disease duration 10.1⯱â¯7.8SD) and 50 age-/sex-matched healthy control subjects consecutively investigated at our University-based Rheumatology Unit. Patients and controls were evaluated for environmental/occupational exposure categories (structured questionnaire), morphological characterization of serum micro-/nanoparticles (Environmental Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy microanalysis), and quantitative assessment of trace elements (inductively coupled plasma atomic emission spectroscopy). RESULTS: Among various categories, only occupational exposure to silica dust was recorded in a significant proportion of SSc patients compared to controls (55% vs. 11%; pâ¯<â¯.0001). Qualitative analysis showed serum silica micro- and nanoparticles in all exposed patients. Quantitative evaluation evidenced significantly higher s-Si levels in SSc patients versus controls (pâ¯<â¯.0001); in addition, higher s-Si levels were detected in patients with occupational exposure (pâ¯<â¯.0001), diffuse cutaneous SSc (pâ¯=â¯.0047), myositis (pâ¯=â¯.0304), and/or lung fibrosis (pâ¯=â¯.0004) compared to those without; notably, the severity of lung fibrosis scoring positively correlated with s-Si levels (pâ¯<â¯.0001). CONCLUSIONS: The study first demonstrated high s-Si levels in exposed SSc patients; this element might represent a pathogenetic co-factor of more severe clinical phenotypes, mainly diffuse scleroderma with lung fibrosis.
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Enfermedades Pulmonares Intersticiales/etiología , Nanopartículas , Esclerodermia Sistémica/etiología , Dióxido de Silicio/sangre , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Masculino , Persona de Mediana Edad , Exposición Profesional , Factores de Riesgo , Esclerodermia Sistémica/sangreRESUMEN
Biohybrids can be defined as the functional combination of proteins, viable cells or microorganisms with non-biological materials. This article reviews recent findings on the encapsulation of microorganisms and eukaryotic cells in inorganic matrices such as silica gels or cements. The entrapment of biological entities into a support material is of great benefit for processing since the encapsulation matrix protects sensitive cells from shear forces, unfavourable pH changes, or cytotoxic solvents, avoids culture-washout, and simplifies the separation of formed products. After reflecting general aspects of such an immobilization as well as the chemistry of the inorganic matrices, we focused on manufacturing aspects and the application of such biohybrids in biotechnology, medicine as well as in environmental science and for civil engineering purpose. STATEMENT OF SIGNIFICANCE: The encapsulation of living cells and microorganisms became an intensively studied and rapidly expanding research field with manifold applications in medicine, bio- and environmental technology, or civil engineering. Here, the use of silica or cements as encapsulation matrices have the advantage of a higher chemical and mechanical resistance towards harsh environmental conditions during processing compared to their polymeric counterparts. In this perspective, the article gives an overview about the inorganic material systems used for cell encapsulation, followed by reviewing the most important applications. The future may lay in a combination of the currently achieved biohybrid systems with additive manufacturing techniques. In a longer perspective, this would enable the direct printing of cell loaded bioreactor components.
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Biotecnología/métodos , Células Inmovilizadas/metabolismo , Células Eucariotas/metabolismo , Dióxido de Silicio/sangre , Células Inmovilizadas/citología , Células Eucariotas/citologíaRESUMEN
BACKGROUND: Pneumatic tube transportation (PTT) may induce hemolysis (H) in blood samples. We aimed to compare the H degree before and after PTT implementation in our hospital. METHODS: Hemolysis indices (HI) for all lithium-heparin plasma samples (P) drawn by the Emergency Department in 2-month periods were retrospectively collected and pre- (n=3579) and post-PTT (n=3469) results compared. The impact of PTT introduction was investigated on LDH [HI threshold (HIt), 25], conjugated bilirubin (cBIL) (HIt, 30), K (HIt, 100) and ALT (HIt, 125). In addition, HI retrieved for P and paired serum samples collected in silica clot activator tubes (S) from the same venipuncture were compared in pre- (n=501) and post-PTT (n=509) periods. RESULTS: Median (5-95th percentile) HI in P was significantly higher in post-PTT period [7 (0-112) vs. 6 (0-82), p<0.001]. Results reported as 'Hemolysis' in P increased from 6.6% in pre-PTT to 9.4% in post-PTT (p<0.001). Investigated tests gave the following rejection rates (pre-PTT vs. post-PTT): LDH, 13.4% vs. 18.8%, p<0.001; cBIL, 9.4% vs. 27.0%, p<0.05; K, 3.7% vs. 5.6%, p<0.001; ALT, 2.9% vs. 4.4%, p<0.01. The slightly higher susceptibility to H of S compared to paired P found in the pre-PTT [9 (1-64) vs. 6 (0-85)] was not confirmed in the post-PTT period [7 (0-90) vs. 8 (1-72)], in which median HI in S was significantly lower (p<0.001) than in pre-PTT. CONCLUSIONS: In our setting PTT promotes H in P, increasing the rate of rejected tests. The use of S appears to protect against the hemolysing effect of PTT.
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Recolección de Muestras de Sangre , Hemólisis , Heparina/sangre , Humanos , Litio/sangre , Dióxido de Silicio/sangreRESUMEN
Nano-silicon dioxide (SiO2) is used nowadays in several biomedical applications such as drug delivery and cancer therapy, and is produced on an industrial scale as additive to paints and coatings, cosmetics and food. Data regarding the long-term biokinetics of SiO2 engineered nanoparticles (ENPs) is lacking. In this study, the whole-body biodistribution of SiO2 core-shell ENPs containing a paramagnetic core of Fe3O4 was investigated after a single exposure via intravenous injection or intratracheal instillation in mice. The distribution and accumulation in different organs was evaluated for a period of 84 days using several techniques, including magnetic resonance imaging, inductively coupled plasma mass spectrometry, X-ray fluorescence and X-ray absorption near edge structure spectroscopy. We demonstrated that intravenously administered SiO2 ENPs mainly accumulate in the liver, and are retained in this tissue for over 84 days. After intratracheal instillation, an almost complete particle clearance from the lung was seen after 84 days with distribution to spleen and kidney. Furthermore, we have strong evidence that the ENPs retain their original core-shell structure during the whole observation period. This work gives an insight into the whole-body biodistribution of SiO2 ENPs and will provide guidance for further toxicity studies.
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Óxido Ferrosoférrico/farmacocinética , Pulmón/metabolismo , Nanopartículas , Dióxido de Silicio/farmacocinética , Administración por Inhalación , Animales , Óxido Ferrosoférrico/administración & dosificación , Óxido Ferrosoférrico/química , Humanos , Inyecciones Intravenosas , Instilación de Medicamentos , Masculino , Ratones , Ratones Endogámicos BALB C , Nanopartículas/administración & dosificación , Nanopartículas/química , Especificidad de Órganos , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/sangre , Dióxido de Silicio/química , Espectrometría por Rayos X , Propiedades de Superficie , Distribución Tisular , Espectroscopía de Absorción de Rayos XRESUMEN
In our study, soluble starch was applied as a novel carbon source for preparing three-dimensional ordered macroporous carbon (3DOMC) using monodisperse silica nanospheres as the hard template. The 3DOMC was used as an insoluble drug carrier when it was found that it could markedly improve the water solubility of felodipine (FDP). The structural features of 3DOMC were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The 3DOMC structure was found to have a higher drug loading than microporous and mesoporous structures, and the interconnected nanostructure effectively inhibited the formation of drug crystals. FDP, belonging to the Biopharmaceutics Classification System II (BCSII), was chosen as the model drug and was loaded into the 3DOMC structure by solvent evaporation. The state of FDP in the 3DOMC structure was characterized by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The results obtained showed that FDP was present in the pores in an amorphous or microcrystalline state. In vivo and in vitro experiments indicated that 3DOMC could significantly improve the drug dissolution rate, but the FDP-3DOMC self-made common tablets had the disadvantage of a burst effect. For this reason, osmotic pump technology was used to control the drug release rate. We developed a potentially useful insoluble drug carrier for pharmaceutical applications.
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Carbono/química , Portadores de Fármacos/síntesis química , Almidón/síntesis química , Agua/química , Administración Oral , Animales , Disponibilidad Biológica , Rastreo Diferencial de Calorimetría/métodos , Carbono/administración & dosificación , Carbono/sangre , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Porosidad , Conejos , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/sangre , Dióxido de Silicio/síntesis química , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Almidón/administración & dosificación , Almidón/sangre , Difracción de Rayos X/métodosRESUMEN
Nanoparticle (NP) pharmacokinetics and biological effects are influenced by many factors, especially surface physicochemical properties. We assessed the effects of an amorphous silica coating on the fate of zinc after intravenous (IV) injection of neutron activated uncoated (65)ZnO or silica-coated (65)ZnO NPs in male Wistar Han rats. Groups of IV-injected rats were sequentially euthanized, and 18 tissues were collected and analyzed for (65)Zn radioactivity. The protein coronas on each ZnO NP after incubation in rat plasma were analyzed by SDS-PAGE gel electrophoresis and mass spectrometry of selected gel bands. Plasma clearance for both NPs was biphasic with rapid initial and slower terminal clearance rates. Half-lives of plasma clearance of silica-coated (65)ZnO were shorter (initial - <1 min; terminal - 2.5 min) than uncoated (65)ZnO (initial - 1.9 min; terminal - 38 min). Interestingly, the silica-coated (65)ZnO group had higher (65)Zn associated with red blood cells and higher initial uptake in the liver. The (65)Zn concentrations in all the other tissues were significantly lower in the silica-coated than uncoated groups. We also found that the protein corona formed on silica-coated ZnO NPs had higher amounts of plasma proteins, particularly albumin, transferrin, A1 inhibitor 3, α-2-hs-glycoprotein, apoprotein E and α-1 antitrypsin. Surface modification with amorphous silica alters the protein corona, agglomerate size, and zeta potential of ZnO NPs, which in turn influences ZnO biokinetic behavior in the circulation. This emphasizes the critical role of the protein corona in the biokinetics, toxicology and nanomedical applications of NPs.
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Proteínas Sanguíneas/metabolismo , Nanopartículas/química , Dióxido de Silicio/sangre , Dióxido de Silicio/química , Óxido de Zinc/sangre , Óxido de Zinc/química , Animales , Electroforesis en Gel de Poliacrilamida , Cinética , Masculino , Tasa de Depuración Metabólica , Nanopartículas/análisis , Corona de Proteínas/metabolismo , Ratas , Ratas Wistar , Propiedades de SuperficieRESUMEN
Engineered nanoparticles are endowed with very promising properties for therapeutic and diagnostic purposes. This work describes a fast and reliable method of analysis by flow cytometry to study nanoparticle interaction with immune cells. Primary immune cells can be easily purified from human or mouse tissues by antibody-mediated magnetic isolation. In the first instance, the different cell populations running in a flow cytometer can be distinguished by the forward-scattered light (FSC), which is proportional to cell size, and the side-scattered light (SSC), related to cell internal complexity. Furthermore, fluorescently labeled antibodies against specific cell surface receptors permit the identification of several subpopulations within the same sample. Often, all these features vary when cells are boosted by external stimuli that change their physiological and morphological state. Here, 50 nm FITC-SiO2 nanoparticles are used as a model to identify the internalization of nanostructured materials in human blood immune cells. The cell fluorescence and side-scattered light increase after incubation with nanoparticles allowed us to define time and concentration dependence of nanoparticle-cell interaction. Moreover, such protocol can be extended to investigate Rhodamine-SiO2 nanoparticle interaction with primary microglia, the central nervous system resident immune cells, isolated from mutant mice that specifically express the Green Fluorescent Protein (GFP) in the monocyte/macrophage lineage. Finally, flow cytometry data related to nanoparticle internalization into the cells have been confirmed by confocal microscopy.
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Citometría de Flujo/métodos , Colorantes Fluorescentes/química , Leucocitos Mononucleares/citología , Microglía/citología , Nanopartículas/química , Adulto , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Fluoresceína-5-Isotiocianato/química , Fluoresceína-5-Isotiocianato/metabolismo , Colorantes Fluorescentes/metabolismo , Humanos , Leucocitos Mononucleares/química , Ratones , Ratones Transgénicos , Microglía/química , Persona de Mediana Edad , Nanopartículas/metabolismo , Dióxido de Silicio/sangre , Dióxido de Silicio/química , Adulto JovenRESUMEN
Silica nanoparticles have an interesting potential in drug delivery, gene therapy and molecular imaging due to the possibility of tailoring their surface reactivity that can be obtained by surface modification. Despite these potential benefits, there is concern that exposure of humans to certain types of silica nanomaterials may lead to significant adverse health effects. The motivation of this study was to determine the kinetics of cellular binding/uptake of the vinyl- and the aminopropyl/vinyl-modified silica nanoparticles into peripheral blood lymphocytes in vitro, to explore their genotoxic and cytotoxic properties and to compare the biological properties of modified silica nanoparticles with those of the unmodified ones. Size of nanoparticles determined by SEM varied from 10 to 50 nm. The average hydrodynamic diameter and zeta potential also varied from 176.7 nm (+18.16 mV) [aminopropyl/vinyl-modified] and 235.4 nm (-9.49 mV) [vinyl-modified] to 266.3 (-13.32 mV) [unmodified]. Surface-modified silica particles were internalized by lymphocytes with varying efficiency and expressed no cytotoxic nor genotoxic effects, as determined by various methods (cell viability, apoptosis/necrosis, oxidative DNA damage, chromosome aberrations). However, they affected the proliferation of the lymphocytes as indicated by a decrease in mitotic index value and cell cycle progression. In contrast, unmodified silica nanoparticles exhibited cytotoxic and genotoxic properties at high doses as well as interfered with cell cycle.
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Portadores de Fármacos/química , Leucocitos Mononucleares/metabolismo , Nanopartículas/química , Nanopartículas/toxicidad , Dióxido de Silicio/química , Dióxido de Silicio/toxicidad , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Aberraciones Cromosómicas/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Portadores de Fármacos/toxicidad , Endotoxinas/análisis , Citometría de Flujo , Humanos , Leucocitos Mononucleares/química , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Índice Mitótico , Necrosis , Tamaño de la Partícula , Dióxido de Silicio/sangre , Dióxido de Silicio/farmacología , Propiedades de SuperficieRESUMEN
Different bioactive molecules are released into living cells from lipid-covered mesoporous silica nanoparticles. The release is triggered by light, as the particles feature covalently attached photosensitizers as membrane-opening agents. It is demonstrated that the particles achieve endosomal escape and that they release their cargo into the cytosol.
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Nanocápsulas/química , Nanocápsulas/efectos de la radiación , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/efectos de la radiación , Protoporfirinas/química , Dióxido de Silicio/sangre , Dióxido de Silicio/efectos de la radiación , Luz , Ensayo de Materiales , Nanocápsulas/ultraestructura , Tamaño de la Partícula , Porosidad/efectos de la radiación , Protoporfirinas/efectos de la radiaciónRESUMEN
The physiological properties of polymer brush-afforded silica particles prepared by surface-initiated living radical polymerization were investigated in terms of the circulation lifetime in the blood and distribution in tissues. Hydrophilic polymers consisting mainly of poly(poly(ethylene glycol) methyl ether methacrylate) were grafted onto silica particles by surface-initiated atom transfer radical polymerization that was mediated by a copper complex to produce hairy hybrid particles. A series of hybrid particles was synthesized by varying the diameter of the silica core and the chain length of the polymer brush to examine the relationship between their physicochemical and physiological properties. The hybrid particles were injected intravenously into mice to investigate systematically their blood clearance and body distribution. It was revealed that the structural features of the hybrid particles significantly affected their in vivo pharmacokinetics. Some hybrid particles exhibited an excellently prolonged circulation lifetime in the blood with a half life of â¼20 h. When such hybrid particles were injected intravenously into a tumor-bearing mouse, they preferentially accumulated in tumor tissue. The tumor-targeted delivery was optically visualized using hybrid particles grafted with fluorescence-labeled polymer brushes.
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Neoplasias del Colon/patología , Radicales Libres/química , Nanopartículas/química , Polímeros/química , Polímeros/farmacocinética , Dióxido de Silicio/sangre , Dióxido de Silicio/farmacocinética , Animales , Femenino , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Metacrilatos/química , Ratones , Ratones Endogámicos BALB C , Polietilenglicoles/química , Polimerizacion , Dióxido de Silicio/química , Propiedades de Superficie , Temperatura , Distribución Tisular , Células Tumorales CultivadasRESUMEN
Nanoparticles (NPs) are decorated with proteins and other biomolecules when they get into contact with biological systems. The presence of proteins in cell culture medium can therefore have effects on the biological outcome in cell-based tests. In this study, the manufactured nanomaterials silicon dioxide (SiO(2)), titanium dioxide (TiO(2)), iron-III-oxide (Fe(2)O(3)), and carbon black (CB) were used to study their interaction with single proteins from bovine and human plasma (albumin, fibrinogen and IgG) as well as with complete human serum. The protein binding capacity of the material was investigated and 1D gel electrophoresis was used to separate the bound proteins and to identify the bands by matrix-assisted laser desorption/ionisation-time-of-flight (MALDI-TOF) mass spectrometry. We found that the NP surface chemistry had a great impact on the amount of bound protein with distinct ligands for each of the tested particles. The hydrophobic CB NPs bound much more protein than the hydrophilic metal oxide NPs. Among the single proteins investigated, fibrinogen showed the strongest affinity for SiO(2), TiO(2) and CB NPs. The identified proteins from human serum adsorbed to these NPs were very different. Only apolipoprotein A1 was found to be adsorbed to all NPs. These studies will help to explain the different degree of biological responses observed after in vitro exposure of cells in the absence or presence of serum and might also support the interpretation of in vivo experiments were NPs come directly into contact with blood plasma.
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Proteínas Sanguíneas/análisis , Nanopartículas/química , Animales , Bovinos , Electroforesis , Compuestos Férricos/sangre , Compuestos Férricos/química , Fibrinógeno/análisis , Fibrinógeno/química , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina G/química , Técnicas In Vitro , Albúmina Sérica/análisis , Albúmina Sérica/química , Dióxido de Silicio/sangre , Dióxido de Silicio/química , Hollín/análisis , Hollín/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Propiedades de Superficie , Titanio/sangre , Titanio/químicaRESUMEN
Solid dispersions were successfully prepared by co-spray-drying of TPGS-stabilized itraconazole nanosuspensions with Aerosil200, followed by heat treatment of the powders. The itraconazole/Aerosil200 weight ratios amounted to 50/50, 30/70, 40/60 and 20/80. The itraconazole content of the powders was close to the expected value, with relative errors between 0.3% and 7.8%. X-ray powder diffraction (XRPD), solid state NMR (SSNMR) and differential scanning calorimetry (DSC) evaluation on the powders revealed the formation of amorphous itraconazole and the absence of glassy itraconazole. Dissolution of the powders was enhanced compared to crystalline and glassy itraconazole (a 2-dimensional structured form of itraconazole). However, no clear trend could be observed between drug loading and dissolution performance of the solid dispersions. Upon storage, conversion to crystalline itraconazole was observed for the 50/50 powder based on XRPD, SSNMR and DSC measurements. Although the 40/60 powder remained X-ray amorphous upon storage, DSC did reveal that a small fraction (7.5+/-1.6% after 10 months of storage) of itraconazole crystallized upon storage. For the 30/70 and 20/80 dispersions, no crystallization could be seen. After 10 months of storage, important changes in the dissolution behavior of the powders were observed. A decrease in dissolution performance was seen for the 50/50 dispersion, which could be attributed to the crystallization of itraconazole. On the other hand, the 40/60, 30/70 and 20/80 dispersions showed an increase in dissolution rate (more than 60% after 10 min). Although not completely clear at this stage, adsorption of itraconazole onto the Aerosil200 surface during storage might be responsible for this behavior. Finally, in vivo experiments were performed in the rat. Oral bioavailability of the 30/70 dispersion was, although lower compared to the marketed Sporanox formulation, significantly enhanced compared to the crystalline drug.
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Química Farmacéutica/métodos , Portadores de Fármacos/química , Itraconazol/química , Dióxido de Silicio/química , Vitamina E/análogos & derivados , Animales , Cristalización , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Estabilidad de Medicamentos , Itraconazol/administración & dosificación , Itraconazol/sangre , Masculino , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Polvos , Ratas , Ratas Wistar , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/sangre , Vitamina E/administración & dosificación , Vitamina E/sangre , Vitamina E/química , Difracción de Rayos XRESUMEN
In 2000, soldiers from a Special Operations Force had airborne lead exposures 20 to 38 times the permissible exposure limit. Their average blood lead level was 13.9 microg/dL. Immediate implementation of pertinent Occupational Safety and Health Administration regulations was recommended. In 2003, investigators learned that the unit also used an outdoor firing range with exposures exceeding the permissible exposure limit. Attempts to conduct more detailed evaluations and control measures were hindered by frequent deployments in the unit and a strong commitment to realistic training. Despite these challenges, the controls implemented resulted in limited success. The average blood lead level in the unit was 6.8 microg/dL in 2005, a reduction of 51%. Proper initial range construction is essential to controlling lead exposures at firing ranges. Occupational health specialists caring for these soldiers must identify, assess, and mitigate exposures from firing ranges while respecting the importance of realistic training.
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Contaminantes Ocupacionales del Aire/análisis , Armas de Fuego , Plomo/análisis , Exposición Profesional/prevención & control , Dióxido de Silicio/análisis , Educación , Humanos , Plomo/sangre , Intoxicación por Plomo/prevención & control , Dióxido de Silicio/sangre , Estados UnidosRESUMEN
The preparation, characterization, and preliminary biomedical application of various nitric oxide (NO)-releasing fumed silica particles (0.2-0.3 microm) are reported. The tiny NO-releasing particles are synthesized by first tethering alkylamines onto the surface of the silica using amine-containing silylation reagents. These amine groups are then converted to corresponding N-diazeniumdiolate groups via reaction with NO(g) at high pressure in the presence of methoxide bases (e.g., NaOMe). N-Diazeniumdiolate groups were found to form more readily with secondary amino nitrogens than primary amino nitrogens tethered to the silica. Different alkali metal cations of the methoxide bases, however, have little effect on the degree of N-diazeniumdiolate formation. The N-diazeniumdiolate moieties attached on the silica surface undergo a primarily proton-driven dissociation to NO under physiological conditions, with an "apparent" reaction order somewhat greater than 1 owing to local increases in pH at the surface of the particles as free amine groups are generated. The rates of N-diazeniumdiolate dissociation are further related to the parent amine structures and the pH of the soaking buffer. The N-diazeniumdiolate groups also undergo slow thermal dissociation to NO, with zero-order dissociation observed at both -15 and 23 degrees C. It is further shown that the resulting NO-releasing fumed silica particles can be embedded into polymer films to create coatings that are thromboresistant, via the release of NO at fluxes that mimic healthy endothelial cells (EC). For example a polyurethane coating containing 20 wt % of NO-releasing particles prepared with pendant hexane diamine structure (i.e., Sil-2N[6]-N(2)O(2)Na) is shown to exhibit improved surface thromboresistivity (compared to controls) when used to coat the inner walls of extracorporeal circuits (ECC) employed in a rabbit model for extracorporeal blood circulation.
Asunto(s)
Materiales Biocompatibles Revestidos/química , Donantes de Óxido Nítrico/química , Dióxido de Silicio/química , Aminas/química , Animales , Compuestos Azo/química , Materiales Biocompatibles Revestidos/síntesis química , Circulación Extracorporea/instrumentación , Circulación Extracorporea/métodos , Concentración de Iones de Hidrógeno , Cinética , Metanol/química , Donantes de Óxido Nítrico/sangre , Donantes de Óxido Nítrico/síntesis química , Nitritos/química , Tamaño de la Partícula , Poliuretanos/química , Conejos , Dióxido de Silicio/sangre , Dióxido de Silicio/síntesis química , Solventes , Relación Estructura-ActividadRESUMEN
Glasses in the binary system CaO-SiO2 for which the molar fraction of CaO is 0 < or = x < or = 0.50, were prepared by means of a sol-gel route starting from tetraethylorthosilicate and calcium nitrate. The textural features of the monoliths obtained were characterized using N2 gas adsorption, helium ultrapycnometry, and mercury porosimetry. In vitro bioactivity tests were performed in simulated body fluid (SBF). The ionic concentration of the SBF after glass immersion was analyzed using inductively coupled plasma atomic emission spectroscopy. The surfaces of the specimens were characterized using X-ray diffraction and scanning electron microscopy coupled with energy dispersive X-ray analysis before and after in vitro testing. The textural characterization revealed that the glasses were mesoporous with cylindrical pores with average diameters ranging from 25 to 663 A depending on the molar fraction of CaO. The in vitro studies showed that all binary CaO-SiO2 gel-glass compositions produced were bioactive. These results indicate that the binary gel-derived CaO-SiO2 system exhibits a level of bioactivity over a similar molar range of SiO2 content as the previously studied ternary CaO-P2O5-SiO2 system.