RESUMO
Numerous types of engineered nanomaterials (ENMs) are commercially available and developments move towards producing more advanced nanomaterials with tailored properties. Such advanced nanomaterials may include chemically doped or modified derivatives with specific surface chemistries; also called higher generation or multiconstituent nanomaterials. To fully enjoy the benefits of nanomaterials, appropriate characterisation of ENMs is necessary for many aspects of their production, use, testing and reporting to regulatory bodies. This chapter introduces both structural and textural properties of nanomaterials with a focus on demonstrating the information that can be achieved by analysis of primary physicochemical characteristics and how such information is critical to understand or assess the possible toxicity of engineered nanomaterials. Many of characterization methods are very specific to obtain particular characteristics and therefore the most widely used techniques are explained and demonstrated.
Assuntos
Nanoestruturas/química , Fenômenos Químicos , HumanosRESUMO
BACKGROUND: The toxicity of dusts from mechanical abrasion of multi-walled carbon nanotube (CNT) epoxy nanocomposites is unknown. We compared the toxic effects of dusts generated by sanding of epoxy composites with and without CNT. The used CNT type was included for comparison. METHODS: Mice received a single intratracheal instillation of 18, 54 and 162 µg of CNT or 54, 162 and 486 µg of the sanding dust from epoxy composite with and without CNT. DNA damage in lung and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Furthermore, the mRNA expression of interleukin 6 and heme oxygenase 1 was measured in the lungs and serum amyloid A1 in the liver. Printex 90 carbon black was included as a reference particle. RESULTS: Pulmonary exposure to CNT and all dusts obtained by sanding epoxy composite boards resulted in recruitment of inflammatory cells into lung lumen: On day 1 after instillation these cells were primarily neutrophils but on day 3, eosinophils contributed significantly to the cell population. There were still increased numbers of neutrophils 28 days after intratracheal instillation of the highest dose of the epoxy dusts. Both CNT and epoxy dusts induced DNA damage in lung tissue up to 3 days after intratracheal instillation but not in liver tissue. There was no additive effect of adding CNT to epoxy resins for any of the pulmonary endpoints. In livers of mice instilled with CNT and epoxy dust with CNTs inflammatory and necrotic histological changes were observed, however, not in mice instilled with epoxy dust without CNT. CONCLUSIONS: Pulmonary deposition of epoxy dusts with and without CNT induced inflammation and DNA damage in lung tissue. There was no additive effect of adding CNT to epoxies for any of the pulmonary endpoints. However, hepatic inflammatory and necrotic histopathological changes were seen in mice instilled with sanding dust from CNT-containing epoxy but not in mice instilled with reference epoxy.
Assuntos
Compostos de Epóxi/toxicidade , Pulmão/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/citologia , Endotoxinas/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/patologia , Camundongos , Microscopia Eletrônica de VarreduraRESUMO
Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 µg/mouse of a small, curled (CNT(Small), 0.8 ± 0.1 µm in length) or large, thick MWCNT (CNT(Large), 4 ± 0.4 µm in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer-Emmett-Teller surface area analysis. Lung tissues were harvested 24h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNT(Small) or CNT(Large) were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNT(Large) elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNT(Small). The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNT(Large), which may eventually lead to the different responses observed at day 28.
Assuntos
Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Pneumonia/induzido quimicamente , Fibrose Pulmonar/induzido quimicamente , Transcrição Gênica/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Dano ao DNA , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Exposição por Inalação/efeitos adversos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Pneumonia/genética , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/patologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Espécies Reativas de Oxigênio , Medição de Risco , Propriedades de Superfície , Fatores de Tempo , Toxicogenética/métodosRESUMO
A method to form ordered mesoporous silica based on the use of folate supramolecular templates has been developed. Evidence based on in situ small-angle X-ray scattering (SAXS), electron microscopy, infrared spectroscopy, and in situ conductivity measurements are used to investigate the organic-inorganic interactions and synthesis mechanism. The behavior of folate molecules in solution differs distinctively from that of surfactants commonly used for the preparation of ordered mesoporous silica phases, notably with the absence of a critical micellar concentration. In situ SAXS studies reveal fluctuations in X-ray scattering intensities consistent with the condensation of the silica precursor surrounding the folate template and the growth of the silica mesostructure in the initial stages. High-angle X-ray diffraction shows that the folate template is well-ordered within the pores even after a few minutes of synthesis. Direct structural data for the self-assembly of folates into chiral tetramers within the pores of mesoporous silica provide evidence for the in register stacking of folate tetramers, resulting in a chiral surface of rotated tetramers, with a rotation angle of 30°. Additionally, the self-assembled folates within pores were capable of adsorbing a considerable amount of CO2 gas through the cavity space of the tetramers. The study demonstrates the validity of using a naturally occurring template to produce relevant and functional mesoporous materials.
Assuntos
Ácido Fólico/química , Dióxido de Silício/química , Espalhamento a Baixo Ângulo , Difração de Raios XRESUMO
Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping with CuO; and whether c) these modifications act synergistically. Mice were exposed by intratracheal instillation and for some doses also oropharyngeal aspiration to: 1) solid silica 100 nm; 2) porous silica 100 nm; 3) porous silica 100 nm with CuO doping; 4) solid silica 300 nm; 5) porous silica 300 nm; 6) solid silica 300 nm with CuO doping; 7) porous silica 300 nm with CuO doping; 8) CuO nanoparticles 9.8 nm; or 9) carbon black Printex 90 as benchmark. Based on a pilot study, dose levels were between 0.5 and 162 µg/mouse (0.2 and 8.1 mg/kg bw). Endpoints included pulmonary inflammation (neutrophil numbers in bronchoalveolar fluid), acute phase response, histopathology, and genotoxicity assessed by the comet assay, micronucleus test, and the gamma-H2AX assay. The porous silica materials induced greater pulmonary inflammation than their solid counterparts. A similar pattern was seen for acute phase response induction and histologic changes. This could be explained by a higher specific surface area per mass unit for the most toxic particles. CuO doping further increased the acute phase response normalized according to the deposited surface area. We identified no consistent evidence of synergism between surface area and CuO doping. In conclusion, porosity and CuO doping each increased the toxicity of silica nanomaterials and there was no indication of synergy when the modifications co-occurred.
Assuntos
Cobre/toxicidade , Nanopartículas/toxicidade , Pneumonia/induzido quimicamente , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Reação de Fase Aguda , Animais , Ensaio Cometa , Cobre/química , Dano ao DNA , Camundongos , Testes para Micronúcleos , Nanopartículas/química , Nanoestruturas , Projetos Piloto , Pneumonia/patologia , PorosidadeRESUMO
Adsorption-mediated CO(2) separation can reduce the cost of carbon capture and storage. The reduction in cost requires adsorbents with high capacities for CO(2) sorption and high CO(2)-over-N(2) selectivity. Amine-modified sorbents are promising candidates for carbon capture. To investigate the details of CO(2) adsorption in such materials, we studied mesocaged (cubic, Pm3n symmetry) silica adsorbents with tethered propylamines using Fourier transform infrared (FTIR) spectroscopy and volumetric uptake experiments. The degree of heterogeneity in these coatings was varied by either cosynthesizing or postsynthetically introducing the propylamine modification. In situ FTIR spectroscopy revealed the presence of both physisorbed and chemisorbed CO(2) in the materials. We present direct molecular evidence for physisorption using FTIR spectroscopy in mesoporous silica sorbents modified with propylamines. Physisorption reduced the CO(2)-over-N(2) selectivity in amine-rich sorbents. Samples with homogeneous coatings showed typical CO(2) adsorption trends and large quantities of IR-observable physisorbed CO(2). The uptake of CO(2) in mesocaged materials with heterogeneous propylamine coatings was higher at high temperatures than at low temperatures. At higher temperatures and low pressures, the postsynthetically modified materials adsorbed more CO(2) than did the extracted ones, even though the surface area after modification was clearly reduced and the coverage of primary amine groups was lower. The principal mode of CO(2) uptake in postsynthetically modified mesoporous silica was chemisorption. The chemisorbed moieties were present mainly as carbamate-ammonium ion pairs, resulting from the quantitative transformation of primary amine groups during CO(2) adsorption as established by NIR spectroscopy. The heterogeneity in the coatings promoted the formation of these ion pairs. The average propylamine-propylamine distance must be small to allow the formation of carbamate-propylammonium ion pairs.
RESUMO
In this study, two sets of methyl-coated non-porous and mesoporous amorphous silica materials of two target sizes (100 and 300 nm; 10-844 m2/g) were used to investigate the potential role of specific surface area (SSA) and porosity on the oral toxicity in mice. Female Swiss mice were administered by oral gavage for 5 consecutive days. Two silica dose levels (100 and 1000 mg/kg b.w.) were tested for all four materials. All dispersions were characterized by transmission electron microscopy (TEM) and Nanoparticle tracking analysis (NTA). Batch dispersions of porous silica were rather unstable due to agglomeration. Animals were sacrificed one day after the last administration or after a three-week recovery period. No relevant toxicological effects were induced by any of the silica materials tested, as evaluated by body weight, gross pathology, relative organ weights (liver, spleen, kidneys), hematology, blood biochemistry, genotoxicity (Comet assay in jejunum cells and micronucleus test in peripheral blood erythrocytes), liver and small intestine histopathology, and intestinal inflammation. The presence of silica particles in the intestine was evaluated by a hyperspectral imaging microscopy system (CytoViva) using histological samples of jejunum tissue. Silica spectral signatures were found in jejunum samples with all the treatments, but only statistically significant in one of the treatment groups.
Assuntos
Jejuno/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Administração Oral , Animais , Ensaio Cometa , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Feminino , Jejuno/patologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/patologia , Camundongos , Testes para Micronúcleos , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho do Órgão , Tamanho da Partícula , Porosidade , Dióxido de Silício/administração & dosagem , Dióxido de Silício/química , Baço/efeitos dos fármacos , Baço/patologia , Propriedades de SuperfícieRESUMO
Hoogsteen-bonded tetrads and pentamers are formed by a large variety of organic molecules through H-donor and acceptor groups capable of inducing self-organization to form columnar and hexagonal mesophases. The biological importance of such macromolecular structures is exemplified by the assembly of guanosine-rich groups of telomere units and their implication in chromosomal replication. Folic acid is composed of a pterin group, chemically and structurally similar to guanine, conjugated to an l-glutamate moiety via a p-amino benzoic acid. Our aim has been to develop a delivery vehicle for folic acid and at the same time provide a novel synthetic route for ordered mesoporous materials without the use of amphiphilic surfactants. We present a new nonsurfactant route for the synthesis of highly ordered mesoporous materials, based on the supramolecular templating of stacked arrays of the tetramer-forming pterin groups of folic acid under a variety of synthetic conditions. This method leads to hexagonally ordered mesoporous structures with gyroid, spherical, and chiral morphologies with pores on the order of 25-30 A in diameter and surface areas above 1000 m(2)/g. More importantly circular dichroism studies reveal that the folate template possesses a chiral signature within the pores in the as-synthesized solid and that chirality is transferred from the folate template to the pore surface via the aminopropyl triethoxysilane costructure directing agent used in the supramolecular assembly. This novel templating approach for ordered mesoporous materials breaks the hegemony of surfactant micellar systems for the preparation of these exciting high surface area solids and opens new opportunities for structural control, design of pore geometry, and novel applications.
Assuntos
Dióxido de Silício/síntese química , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Estrutura Molecular , Tamanho da Partícula , Porosidade , Dióxido de Silício/química , Propriedades de SuperfícieRESUMO
We present here a detailed study of the controlled release of amino acid derived amphiphilic molecules from the internal pore structure of mesoporous nanoparticle drug delivery systems with different structural properties; namely cubic and hexagonal structures of various degrees of complexity. The internal pore surface of the nanomaterials presented has been functionalised with amine moieties through a one pot method. Release profiles obtained by Alternating Ionic Current measurements are interpreted in terms of specific structural and textural parameters of the porous nanoparticles such as pore geometry and connectivity. Results indicate that diffusion coefficients are lower by as much as four orders of magnitude in 2-dimensional structures in comparison to 3-dimensional mesoporous solids. A fast release in turn is observed from mesocaged materials AMS-9 and AMS-8 where the presence of structural defects is thought to lead to a slightly lower diffusion coefficient in the latter. Amount of pore wall functionalisation and number of binding sites on the model drug are found to have little effect on the drug release rate.
Assuntos
Preparações de Ação Retardada , Nanopartículas , Algoritmos , Condutividade Elétrica , Cinética , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nitrogênio/química , Tamanho da Partícula , Termodinâmica , Termogravimetria , Difração de Raios XRESUMO
The first part of this study was dedicated to the modelling of the influence of particle shape, porosity and particle size distribution on the volume specific surface area (VSSA) values in order to check the applicability of this concept to the identification of nanomaterials according to the European Commission Recommendation. In this second part, experimental VSSA values are obtained for various samples from nitrogen adsorption isotherms and these values were used as a screening tool to identify and classify nanomaterials. These identification results are compared to the identification based on the 50% of particles with a size below 100 nm criterion applied to the experimental particle size distributions obtained by analysis of electron microscopy images on the same materials. It is concluded that the experimental VSSA values are able to identify nanomaterials, without false negative identification, if they have a mono-modal particle size, if the adsorption data cover the relative pressure range from 0.001 to 0.65 and if a simple, qualitative image of the particles by transmission or scanning electron microscopy is available to define their shape. The experimental conditions to obtain reliable adsorption data as well as the way to analyze the adsorption isotherms are described and discussed in some detail in order to help the reader in using the experimental VSSA criterion. To obtain the experimental VSSA values, the BET surface area can be used for non-porous particles, but for porous, nanostructured or coated nanoparticles, only the external surface of the particles, obtained by a modified t-plot approach, should be considered to determine the experimental VSSA and to avoid false positive identification of nanomaterials, only the external surface area being related to the particle size. Finally, the availability of experimental VSSA values together with particle size distributions obtained by electron microscopy gave the opportunity to check the representativeness of the two models described in the first part of this study. They were also used to calculate the VSSA values and these calculated values were compared to the experimental results. For narrow particle size distributions, both models give similar VSSA values quite comparable to the experimental ones. But when the particle size distribution broadens or is of multi-bimodal shape, as theoretically predicted, one model leads to VSSA values higher than the experimental ones while the other most often leads to VSSA values lower than the experimental ones. The experimental VSSA approach then appears as a reliable, simple screening tool to identify nano and non-nano-materials. The modelling approach cannot be used as a formal identification tool but could be useful to screen for potential effects of shape, polydispersity and size, for example to compare various possible nanoforms.
RESUMO
Mesoporous silica-based particles are promising candidates for biomedical applications. Here, we address the importance of macrophage activation status for internalization of AMS6 (approx. 200 nm in diameter) versus AMS8 (approx. 2 µm) mesoporous silica particles and the role of different phagocytosis receptors for particle uptake. To this end, FITC-conjugated silica particles were used. AMS8 were found to be non-cytotoxic both for M-CSF-stimulated (anti-inflammatory) and GM-CSF-stimulated (pro-inflammatory) macrophages, whereas AMS6 exhibited cytotoxicity towards M-CSF-stimulated, but not GM-CSF-stimulated macrophages; this toxicity was, however, mitigated in the presence of serum. AMS8 triggered the secretion of pro-inflammatory cytokines in M-CSF-activated cells. Class A scavenger receptor (SR-A) expression was noted in both M-CSF and GM-CSF-stimulated macrophages, although the expression was higher in the former case, and gene silencing of SR-A resulted in a decreased uptake of AMS6 in the absence of serum. GM-CSF-stimulated macrophages expressed higher levels of the mannose receptor CD206 compared to M-CSF-stimulated cells, and uptake of AMS6, but not AMS8, was reduced following the downregulation of CD206 in GM-CSF-stimulated cells; particle uptake was also suppressed by mannan, a competitive ligand. These studies demonstrate that macrophage activation status is an important determinant of particle uptake and provide evidence for a role of different macrophage receptors for cell uptake of silica particles.
Assuntos
Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/química , Macrófagos/imunologia , Nanopartículas/química , Nanopartículas/ultraestrutura , Dióxido de Silício/química , Células Cultivadas , Humanos , Nanopartículas/administração & dosagem , Nanoporos/ultraestrutura , Tamanho da Partícula , Porosidade , Dióxido de Silício/administração & dosagemRESUMO
Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 µg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (-OH and -COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.
Assuntos
Quebras de DNA , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Pneumonia/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Ensaio Cometa , Relação Dose-Resposta a Droga , Feminino , Exposição por Inalação/análise , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Nanotubos de Carbono/química , Infiltração de Neutrófilos/imunologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Tamanho da Partícula , Pneumonia/imunologia , Análise de Regressão , Propriedades de SuperfícieRESUMO
We applied transcriptional profiling to elucidate the mechanisms associated with pulmonary responses to titanium dioxide (TiO2 ) nanoparticles (NPs) of different sizes and surface coatings, and to determine if these responses are modified by NP size, surface area, surface modification, and embedding in paint matrices. Adult C57BL/6 mice were exposed via single intratracheal instillations to free forms of TiO2 NPs (10, 20.6, or 38 nm in diameter) with different surface coatings, or TiO2 NPs embedded in paint matrices. Controls were exposed to dispersion medium devoid of NPs. TiO2 NPs were characterized for size, surface area, chemical impurities, and agglomeration state in the exposure medium. Pulmonary transcriptional profiles were generated using microarrays from tissues collected one and 28 d postexposure. Property-specific pathway effects were identified. Pulmonary protein levels of specific inflammatory cytokines and chemokines were confirmed by ELISA. The data were collapsed to 659 differentially expressed genes (P ≤ 0.05; fold change ≥ 1.5). Unsupervised hierarchical clustering of these genes revealed that TiO2 NPs clustered mainly by postexposure timepoint followed by particle type. A pathway-based meta-analysis showed that the combination of smaller size, large deposited surface area, and surface amidation contributes to TiO2 NP gene expression response. Embedding of TiO2 NP in paint dampens the overall transcriptional effects. The magnitude of the expression changes associated with pulmonary inflammation differed across all particles; however, the underlying pathway perturbations leading to inflammation were similar, suggesting a generalized mechanism-of-action for all TiO2 NPs. Thus, transcriptional profiling is an effective tool to determine the property-specific biological/toxicity responses induced by nanomaterials.
Assuntos
Inflamação/genética , Pulmão/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Titânio/efeitos adversos , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/patologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Análise Serial de TecidosRESUMO
BACKGROUND: Mesoporous silica particles are highly promising nanomaterials for biomedical applications. They can be used to improve bioavailability, solubility and drug stability and to protect drugs from the acidic conditions of the stomach, leading to increased drug effectiveness. Their biocompatibility in vivo has recieved little attention, in particular regarding oral administration. AIM: To study the oral tolerance of micron-sized nanoporous folic acid-templated material-1 (cylindrical, 2D hexagonal pore structure) and nanometer-sized anionic-surfactant-templated mesoporous silica material-6 (cylindrical, 3D cubic pore structure) mesoporous silica particles in Sprague Dawley rats. MATERIALS & METHODS: A dose stepwise procedure or range finding test was followed by a consequent confirmatory test. The confirmatory test included daily administrations of 2000 and 1200 mg/kg doses for nanoporous folic acid-templated material-1 and anionic-surfactant-templated mesoporous silica material-6, respectively. RESULTS: The maximum tolerated dose for anionic-surfactant-templated mesoporous silica material-6 was not reached. Similar results were observed for nanometer-sized anionic-surfactant-templated mesoporous silica material-1 in most of the animals, although adverse effects were observed in some animals that are most probably due to the administration by oral gavage of the formulated particles. CONCLUSION: The results are promising for the use of mesoporous silica materials as drug-delivery systems in oral administration.
Assuntos
Dióxido de Silício/administração & dosagem , Administração Oral , Animais , Portadores de Fármacos , Microscopia Eletrônica de Varredura , Ratos , Ratos Sprague-DawleyRESUMO
The synthesis of cubic Pm3n mesocaged solid templated by cetyltrimethyl ammonium bromide (C16TMABr) surfactant by direct cocondensation of (3-aminopropyl)triethoxysilanes (APES) under strong alkaline conditions is reported. The novel route gives direct incorporation of amino functional groups on the porous silica wall, and the structural formation has been followed by means of in situ SAXS studies performed at a synchrotron beam line. Data shows that a molar ratio of C16TMABr/APES = 0.6 favors the formation of 3D cubic mesocaged solid with Pm3n symmetry which transforms to a cylindrical mesoporous phase with p6mm symmetry at higher molar ratios. Further structural evaluation has been performed by means electron crystallography (EC). Reconstructed 3D models based on EC show the presence of spherical cages (A-cages, 45 angstroms) and ellipsoidal cages (B-cages, 48 x 43 angstroms) whereby every cage in the unit cell is connected to 14 nearest cages with a window size of 18 angstroms. Finally, a mechanism is proposed, denoted S+ approximately NoI-, in which penetration of the neutral aminopropyl moiety within the micellar corona is responsible for the formation of the Pm3n phase, accounting for the formation of the hexagonal phase at higher molar ratios and higher temperatures. In comparison to other mesocaged materials with the same symmetry this structure possesses a more open porous network which will help assess its potential in a variety of applications discussed herein.
RESUMO
A new method to investigate the effect of pore geometry on diffusion processes in mesoporous silica nanoparticles and other types of micro- and mesoporous structures is put forward. The method is based on the study of proton diffusion from a liquid surrounding the mesoporous particles into the particle pore system. The proton diffusion properties are assessed for a variety of as-synthesized mesoporous nano- and microparticles with two-dimensional and three-dimensional connectivity. Results show that the diffusion coefficients are higher for the proton absorption process than for the release of surfactant template molecules, and that they overall follow the same trend with the more complex three-dimensional mesocaged particles showing the highest diffusion coefficients. The pore geometry (cylindrical pores versus cage-type pores) and structure connectivity are found to play a key role for the effects observed. The results put forward in the present work should offer a valuable tool in the development of porous nanomaterials in a range of applications including the use as catalysis and separation enhancers in the petrochemical industry, as scaffolds for hydrogen storage, and as drug delivery vehicles for sustained release and gene transfection.
Assuntos
Nanopartículas/química , Nanoestruturas/química , Dióxido de Silício/química , Absorção , Catálise , Difusão , Sistemas de Liberação de Medicamentos , Hidrogênio/química , Concentração de Íons de Hidrogênio , Micelas , Microscopia Eletrônica de Varredura , Nanotecnologia/métodos , Tamanho da Partícula , Prótons , Fatores de TempoRESUMO
We present here a study of the controlled release of amino acid-derived amphiphilic molecules from the internal pore structure of mesoporous nanoparticle drug delivery systems with different structural properties, namely cubic and hexagonal structures of various degrees of complexity. The internal pore surface of the nanomaterials presented has been functionalised with amine moieties through a one-pot method. Release profiles obtained by conductivity measurements are interpreted in terms of specific structural and textural parameters of the porous nanoparticles, such as pore geometry and connectivity. Results indicate that diffusion coefficients are lower by as much 4 orders of magnitude in two-dimensional structures in comparison to three-dimensional mesoporous solids. A fast release in turn is observed from mesocaged materials AMS-9 and AMS-8, where the presence of structural defects is thought to lead to a slightly lower diffusion coefficient in the latter. We conclude that the use of single or mixed phases of these porous systems can be utilized to provide sustained release over long time periods and expect their use in a variety of formulations.