Nonporous Silica Research Articles

An Evaluation of the in vivo Safety of Nonporous Silica Nanoparticles: Ocular Topical Administration versus Oral Administration

Nonporous silica nanoparticles (SiNPs) have potential as promising carriers for ophthalmic drugs. However, the in vivo safety of ocular topical SiNPs remains unclear. This study investigated the in vivo safety of oral and ocular topical applications of 100 nm-sized SiNPs in Sprague-Dawley rats. The rats were divided into the following four groups: low-dose oral administration (total 100 mg/kg of SiNPs mixed with food for one week), high-dose oral administration (total 1000 mg/kg of SiNPs mixed with food for one week), ocular topical administration (10 mg/ml concentration, one drop, applied to the right eyes four times a day for one month), or a negative control (no SiNP treatment). The rats were observed for 12 weeks to investigate any signs of general or ocular toxicity. During the observation period, no differences were observed in the body weights, food and water intakes, behaviors and abnormal symptoms of the four groups. No animal deaths occurred. After 12 weeks, hematologic, blood biochemical parameters and ophthalmic examinations revealed no abnormal findings in any of the animals. The lack of toxicity of the SiNPs was further verified in autopsy findings of brain, liver, lung, spleen, heart, kidneys, intestine, eyeballs, and ovaries or testes.

Synthesis of wrinkled mesoporous silica and its reinforcing effect for dental resin composites

ObjectiveThe aim of this work is to explore the reinforcing effect of wrinkled mesoporous silica (WMS), which should allow micromechanical resin matrix/filler interlocking in dental resin composites, and to investigate the effect of silica morphology, loading, and compositions on their mechanical properties. MethodsWMS (average diameter of 496nm) was prepared through the self-assembly method and characterized by the use of the electron microscopy, dynamic light scattering, and the N2 adsorption–desorption measurements. The mechanical properties of resin composites containing silanized WMS and nonporous smaller silica were evaluated with a universal mechanical testing machine. Field-emission scanning electron microscopy was used to study the fracture morphology of dental composites. Resin composites including silanized silica particles (average diameter of 507nm) served as the control group. ResultsHigher filler loading of silanized WMS substantially improved the mechanical properties of the neat resin matrix, over the composites loaded with regular silanized silica particles similar in size. The impregnation of smaller secondary silica particles with diameters of 90 and 190nm, denoted respectively as Si90 and Si190, increased the filler loading of the bimodal WMS filler (WMS-Si90 or WMS-Si190) to 60wt%, and the corresponding composites exhibited better mechanical properties than the control fillers made with regular silica particles. Among all composites, the optimal WMS-Si190- filled composite (mass ratio WMS:Si190=10:90, total filler loading 60wt%) exhibited the best mechanical performance including flexural strength, flexural modulus, compressive strength and Vickers microhardness. SignificanceThe incorporation of WMS and its mixed bimodal fillers with smaller silica particles led to the design and formulation of dental resin composites with superior mechanical properties.

How Can Doxorubicin Loading Orchestrate in Vitro Degradation Behaviors of Mesoporous Silica Nanoparticles under a Physiological Condition?

In the field of drug-delivery research, mesoporous silica nanoparticles (MSNs) have received a great deal of attention because of their capability to load and release drug molecules through the internal mesopores. To maximize the biomedical applicability of MSN-based drug carriers, it is important to ensure their degradability in a physiological environment as well as to obtain MSNs with desirable physicochemical properties. We present in vitro degradability of drug-loaded MSNs (DMSNs) that contain an anticancer drug (doxorubicin) in the pores and are suspended in physiological media (i.e., PBS at 37 °C). To obtain comprehensive understanding of the degradation process of DMSNs, cargo-free MSNs and nonporous solid silica nanoparticles (SSNs) were studied comparatively. Degradation of each particle was studied by using ICP, TEM, and gas sorption measurement and analyzed in terms of structural parameters, external particle surface dissolution, and acidity of the PBS. It is demonstrated for the first time that drug loading into the pores leads to better degradability of MSNs by combining each distinct advantage of bare MSNs and SSNs to make DMSNs simultaneously possess an initial degradation rate as fast as drug-unloaded MSNs and a total degradation quantity as high as SSNs. The presented data not only demonstrate a high biodegradability of MSN-based drug carriers but also provide new insights into their unique in vitro degradation pattern.

Enhanced Acrylate Production from 2-Acetoxypropanoic Acid Esters

Reaction conditions and reactor geometry for producing acrylates in high yield from lactic acid-derived 2-acetoxypropanoic acid (APA) esters are presented. An acrylate ester yield of 75% is achieved from methyl and benzyl APA esters at 550 °C in a fixed bed reactor filled with nonporous silica particles, carbon dioxide as a diluent gas, and acetic acid as a co-feed with the APA ester. The yield from methyl and benzyl APA esters is remarkably higher than from ethyl or butyl esters of APA, which have hydrogen atoms on the β-carbon of the ester functional group and thus can undergo alkene elimination, leading to reduced acrylate yield. Under optimum conditions, APA conversion to acrylates is stable over 30 h of continuous operation with little carbon deposition on the contact material.

Superparamagnetic nanohybrids with cross-linked polymers providing higher in vitro stability

A simple, rapid, reproducible, and scalable method for generating highly stable cross-linked superparamagnetic nanohybrids was developed. Pre-coating of superparamagnetic iron oxide nanoparticle surfaces with a biocompatible polymer, hydroxy polyvinyl alcohol (PVA-OH) prior to cross-linking with silica precursor resulted in improved stability, uniform morphologies and allows for further surface functionalization. The obtained magnetic nanohybrids contain a non-porous silica layer, are monodisperse (size 50.0 ± 3.7 nm), and show colloidal stability applicable for biomedical applications (pH 7.35–7.45) with long shelf life (>9 months). In vitro studies indicate that as-prepared nanohybrids are non-cytotoxic and highly robust toward endosomal/lysosomal conditions, with no particle dissolution evident for up to 42 days. As a demonstration of the potential utility of these nanohybrids in medical diagnostic applications (e.g., MRI), surface functionalization with folic acid resulted in particle recognition and affinity to folate receptor-positive cervix (HeLa) cells. Accordingly, the facile development of these non-toxic, stable cross-linked magnetic nanohybrids, with the added benefit of scalable preparation, should serve as an entry point for the further development of safer, target specific, MRI contrast agents for cancer diagnosis.

Synthesis, characterization and cellular cytotoxicity evaluation of a new magnetic nanoparticle carrier co-functionalized with amine and folic acid

In the present work, for the first time, co-functionalizing the surface of a core-shell Fe3O4@nSiO2 nanoparticle was performed for transporting doxorubicin anticancer drug (DOX). This core-shell nanoparticle (NP) is composed of superparamagnetic iron oxide core synthesized by solvothermal method and a nonporous silica (nSiO2) layer shell. The nanocomposite shell was co-functionalized with amine group (NH) and folic acid (FA). The characterization results confirmed the super-paramagnetic property of Fe3O4@nSiO2 nanoparticle with the average particle size of 75 nm. In addition, the successful co-functionalizing the surface of NPs was confirmed with FTIR analysis. Dox loading on the nanocomposite was performed at the optimum adsorption condition with the entrapment efficiency of 81.5%. In vitro release study showed a very slow release at pH = 7.4 while a relative rapid release within 10 h and a sustained release until 144 h was observed at pH = 5.5. Finally, the in vitro cytotoxicity assay showed that cellular cytotoxicity of DOX-loaded Fe3O4@nSiO2-NHFA on the breast cancer cell lines (MDA-MB-231) is increased considerably in comparison to free DOX. This confirms the improvement of the synthesized nanocomposite structure. All results confirmed that this new synthesized nanoparticle with an appropriate size and cellular cytotoxicity is a suitable candida for drug-delivery vehicles.

The Effects of Nonporous Silica Nanoparticles on Cultured Human Keratocytes.

Silica nanoparticles (SiNPs) are promising carriers for ophthalmic drug delivery. In this study, we investigated the effect of various sizes of nonporous SiNPs on cultured human keratocytes. Three different sizes of SiNPs (50, 100, and 150 nm) were manufactured. Primarily cultured human keratocytes were exposed to different concentrations (0, 25, 50, and 100 μg/mL) of three sizes of SiNPs for up to 72 hours. Intracellular reactive oxygen species (ROS) generation, cellular viability, lactate dehydrogenase (LDH) assay, autophagy, vimentin expression, and mammalian target of rapamycin (mTOR) pathway activation were evaluated. Intracellular distribution of SiNPs was evaluated with transmission electron microscopy. Transmission electron microscopy revealed SiNPs were taken up by keratocytes inside cytoplasmic vacuoles. Neither nuclear entry of SiNPs nor mitochondrial structural damage was observed. Both intracellular ROS generation and LDH level remained unchanged with up to 100 μg/mL SiNP treatment. Cellular viability was not affected by SiNP treatment. Autophagy showed significant dose-dependent activation with 50- and 100-nm SiNPs. However, mTOR activation remained unchanged. Vimentin expression did not show any significant increase with SiNPs. Our findings suggested that 50-, 100-, and 150-nm SiNPs did not induce significant cytotoxicity in cultured human keratocytes at concentrations up to 100 μg/mL.

Multifunctional silica nanoparticles as a promising theranostic platform for biomedical applications

Recent advances in the use of nonporous silica nanoparticles as theranostic platforms for various biomedical applications, particularly in drug delivery, bioimaging and bio-adhesives.

Covalent Immobilization of Human Placental 17β-Hydroxysteroid Dehydrogenase Type 1 onto Glutaraldehyde Activated Silica Coupled with LC-TOF/MS for Anti-Cancer Drug Screening Applications.

Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), a potential target in breast cancer prevention and therapy, was extracted from human placenta and immobilized on nonporous silica (∼5μm) with a covalent method for the first time. The optimum initial enzyme concentration and immobilization time during the immobilization process were 0.42mgmL-1 and 12h, repectively. The binding was confirmed by scanning electron microscope (SEM) and infrared spectroscopy (FT-IR). It could improve the pH, thermal and storage stability compared to free enzyme. Moreover, the immobilized enzyme could be reused at least four times. A screening method based on it coupled with liquid chromatography-time-of-flight mass spectrometer (LC-TOF/MS) was established, and the half-maximal inhibitory concentration (IC 50) of apigenin for the immobilized enzyme was 291nM. Subsequently, 10 natural products were evaluated leading to inhibition of the activity of 17β-HSD1 at the concentration of 25μM, and six of them inhibit the activity over 50%.

Protein-Containing Lipid Bilayers Intercalated with Size-Matched Mesoporous Silica Thin Films.

Proteins are key components in a multitude of biological processes, of which the functions carried out by transmembrane (membrane-spanning) proteins are especially demanding for investigations. This is because this class of protein needs to be incorporated into a lipid bilayer representing its native environment, and in addition, many experimental conditions also require a solid support for stabilization and analytical purposes. The solid support substrate may, however, limit the protein functionality due to protein-material interactions and a lack of physical space. We have in this work tailored the pore size and pore ordering of a mesoporous silica thin film to match the native cell-membrane arrangement of the transmembrane protein human aquaporin 4 (hAQP4). Using neutron reflectivity (NR), we provide evidence of how substrate pores host the bulky water-soluble domain of hAQP4, which is shown to extend 7.2 nm into the pores of the substrate. Complementary surface analytical tools, including quartz crystal microbalance with dissipation monitoring (QCM-D) and fluorescence microscopy, revealed successful protein-containing supported lipid bilayer (pSLB) formation on mesoporous silica substrates, whereas pSLB formation was hampered on nonporous silica. Additionally, electron microscopy (TEM and SEM), light scattering (DLS and stopped-flow), and small-angle X-ray scattering (SAXS) were employed to provide a comprehensive characterization of this novel hybrid organic-inorganic interface, the tailoring of which is likely to be generally applicable to improve the function and stability of a broad range of membrane proteins containing water-soluble domains.

Durable Superhydrophobic Particles Mimicking Leafhopper Surface: Superoleophilicity and Very Low Surface Energy

The powder coating on brochosomes of leafhopper can repel water, diiodomethane (DM), and ethylene glycol (EG) droplets with contact angle >150°. This is attributed to the very low surface energy as low as <1.0 mN m–1 and their porous honeycomb structure. In this work, grafted silica nanoparticles with properties similar to leafhopper (LH) particle coating is synthesized in a single step by catalytic grafting of stearic acid on nonporous silica nanoparticles. The particles repel water, diiodomethane, and ethylene glycol with contact angle 167°, 161°, and 157°, respectively. The surface energy is also found as <1.0 mN m–1. The particle coating shows sliding angle <10° with these probe liquids. The superhydrophobic particles are resistant to pH = 1 to 13, boiling water conditions and preserves super-repelling nature to reference liquids after the treatments. In a mixture of hexane/water or kerosene/water, the particles completely wet the oleophilic part and repel water layer due to superoleophilic–superhydro...

Immobilization of proline-specific endoprotease on nonporous silica nanoparticles functionalized with amino group.

Enzyme immobilization is believed to provide an excellent base for increasing environmental tolerance of enzyme and considerable period of time. In this work, a kind of nonporous silica nanoparticles functionalized with amino group was synthesized to immobilize proline-specific endoprotease (PSEP). PSEP is known to specifically cleave peptides (or esters) at the carboxyl side of proline, thus can prevent the formation of haze and prolong the shelf life of beer. After immobilization, the environmental tolerance (temperature and pH, respectively) was obviously improved, and the immobilized enzyme can retain above 90% of its original activity after 6 uses. Moreover, the immobilized enzyme can effectively prevent the formation of chill-haze using fresh beer fermentation liquid.

The Influence of Zeolites on Radical Formation During Lignin Pyrolysis.

Lignin from lignocellulosic biomass is a promising source of energy, fuels, and chemicals. The conversion of the polymeric lignin to fuels and chemicals can be achieved by catalytic and noncatalytic pyrolysis. The influence of nonporous silica and zeolite catalysts, such as silicalite, HZSM5, and HUSY, on the radical and volatile product formation during lignin pyrolysis was studied by in situ high-temperature electron paramagnetic resonance spectroscopy (HTEPR) as well as GC-MS. Higher radical concentrations were observed in the samples containing zeolite compared to the sample containing only lignin, which suggests that there is a stabilizing effect by the inorganic surfaces on the formed radical fragments. This effect was observed for nonporous silica as well as for HUSY, HZSM5, and silicalite zeolite catalysts. However, the effect is far larger for the zeolites owing to their higher specific surface area. The zeolites also showed an effect on the volatile product yield and the product distribution within the volatile phase. Although silicalite showed no effect on the product selectivity, the acidic zeolites such as HZSM5 or HUSY increased the formation of deoxygenated products such as benzene, toluene, xylene (BTX), and naphthalene.

Supercritical Fluid Atomic Layer Deposition: Base-Catalyzed Deposition of SiO2.

An in situ FTIR thin film technique was used to study the sequential atomic layer deposition (ALD) reactions of SiCl4, tetraethyl orthosilicate (TEOS) precursors, and water on nonporous silica powder using supercritical CO2 (sc-CO2) as the solvent. The IR work on nonporous powders was used to identify the reaction sequence for using a sc-CO2-based ALD to tune the pore size of a mesoporous silica. The IR studies showed that only trace adsorption of SiCl4 occurred on the silica, and this was due to the desiccating power of sc-CO2 to remove the adsorbed water from the surface. This was overcome by employing a three-step reaction scheme involving a first step of adsorption of triethylamine (TEA), followed by SiCl4 and then H2O. For TEOS, a three-step reaction sequence using TEA, TEOS, and then water offered no advantage, as the TEOS simply displaced the TEA from the silica surface. A two-step reaction involving the addition of TEOS followed by H2O in a second step did lead to silica film growth. However, higher growth rates were obtained when using a mixture of TEOS/TEA in the first step. The hydrolysis of the adsorbed TEOS was also much slower than that of the adsorbed SiCl4, and this was overcome by using a mixture of water/TEA during the second step. While the three-step process with SiCl4 showed a higher linear growth rate than obtained with two-step process using TEOS/TEA, its use was not practical, as the HCl generated led to corrosion of our sc-CO2 delivery system. However, when applying the two-step ALD reaction using TEOS on an MCM-41 powder, a 0.21 nm decrease in pore diameter was obtained after the first ALD cycle whereas further ALD cycles did not lead to further pore size reduction. This was attributed to the difficulty in removal of the H2O in the pores after the first cycle.

Mathematical modeling of the gas transport through PEBAX/(nonporous silica) nanocomposite membranes: Development based on Van Amerongen and Van Krevelen relations

This study tries to develop an explicit and phenomenological model to describe transport properties of penetrants through nanocomposite membranes. The model development procedure was conducted regarding experimental observations. Poly(Ether Block Amid), PEBAX (grade 1657), and SiO2 nanoparticles were applied to fabricate the neat and the nanocomposite membranes. Permeability, solubility and diffusivity of four permanent gases (CO2, H2, N2 and CH4) were measured through the fabricated membranes at temperature range of (298–338 K), and a fixed transmembrane pressure (TMP) of 2 bar. The proposed model was developed based on the solution-diffusion theory, to calculate solubility, diffusivity and permeability of the penetrants through the nanocomposite membranes. The Van Amerongen and Van Krevelen relations were applied to estimate solution and diffusion coefficients of the penetrants through the neat membrane regarding the physical properties of penetrants and glass transition temperature of the polymer. Then, solution and diffusion coefficients through the nanocomposite membranes were correlated to those of the neat membrane and structural properties of the nanocomposite membranes. The results showed that the presented model in this study can efficiently calculate solubility, diffusivity and then permeability of the penetrants through the fabricated nanocomposite membranes (e.g. the calculated values and the experimental data have a correlation coefficient, R2, higher than 0.95, 0.97, and 0.96 for solubility, diffusivity and permeability, respectively).

Magnetic Core-Shell to Yolk-Shell Structures in Palladium-Catalyzed Suzuki-Miyaura Reactions: Heterogeneous versus Homogeneous Nature.

This study describes a comparative investigation on the heterogeneous versus homogeneous nature of the Pd-catalyzed Suzuki-Miyaura cross-coupling reaction mechanism with specific magnetic hierarchical core-shell and yolk-shell structures. The hierarchical core-shell Fe3 O4 @SiO2 -Pd@mCeO2 (m=mesoporous) catalyst contains a core of nonporous silica-sheltered magnetite (Fe3 O4 ) nanoparticles (NPs), a transition layer of active palladium (Pd) NPs, and an outer shell of porous ceria (CeO2 ). The magnetic yolk-shell Fe3 O4 @h-Pd@mCeO2 (h=hollow) catalyst was prepared by selectively etching the nonporous silica interlayers. Notably, the results of the hot-filtration heterogeneity test, the effect of Pd concentration, and solid-phase poisoning, indicate that the two kinds of catalysts function in Pd-catalyzed Suzuki-Miyaura cross-coupling reactions through different catalytic mechanisms. Moreover, both catalysts demonstrated better catalytic activity than the Fe3 O4 @SiO2 -Pd catalyst. This finding can be ascribed to the outermost CeO2 shell having a high concentration of trivalent cerium and oxygen vacancies, which gives rise to the increased electron density of Pd NPs, and a faster rate-determining step in the oxidative addition reaction for the Suzuki reaction. In addition, we propose a feasible mechanism elucidating the synergistic effect between the supporting CeO2 and active species.

Membrane interactions of mesoporous silica nanoparticles as carriers of antimicrobial peptides

Membrane interactions are critical for the successful use of mesoporous silica nanoparticles as delivery systems for antimicrobial peptides (AMPs). In order to elucidate these, we here investigate effects of nanoparticle charge and porosity on AMP loading and release, as well as consequences of this for membrane interactions and antimicrobial effects. Anionic mesoporous silica particles were found to incorporate considerable amounts of the cationic AMP LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (LL-37), whereas loading is much lower for non-porous or positively charged silica nanoparticles. Due to preferential pore localization, anionic mesoporous particles, but not the other particles, protect LL-37 from degradation by infection-related proteases. For anionic mesoporous nanoparticles, membrane disruption is mediated almost exclusively by peptide release. In contrast, non-porous silica particles build up a resilient LL-37 surface coating due to their higher negative surface charge, and display largely particle-mediated membrane interactions and antimicrobial effects. For positively charged mesoporous silica nanoparticles, LL-37 incorporation promotes the membrane binding and disruption displayed by the particles in the absence of peptide, but also causes toxicity against human erythrocytes. Thus, the use of mesoporous silica nanoparticles as AMP delivery systems requires consideration of membrane interactions and selectivity of both free peptide and the peptide-loaded nanoparticles, the latter critically dependent on nanoparticle properties.

Dissolution kinetics of mesoporous silica nanoparticles in different simulated body fluids

The application of mesoporous silica nanoparticles as a platform for drug delivery and bioimaging requires a good understanding of the degradability of these particles under physiological conditions. Optimally, the degradability should be studied in vivo using relevant administration routes and dosings, but such studies are complicated and expensive. Thus, the biodegradability is often studied in vitro using simulated body fluids. However, such studies are scarce to date, and the results are partially conflicting. The aims of this study were therefore (a) to determine the influence of the composition of different simulated body fluids on the observed silica dissolution rates and (b) to establish morphological key parameters that determine the dissolution kinetics of silica nanoparticles. As dissolution media, simulated body fluid (SBF), simulated lung fluid (SLF), simulated gastric juice (SGF) and PBS buffer were used, and the silica concentration was kept below the silica saturation limit. Three mesoporous silica particles of different sizes were studied together with one non-porous Stober-type silica particle. The observed silica dissolution rates followed the order SLF > SBF ≈ PBS ≫ SGF. Apart from general pH effects, the presence of organic acids in SLF is suggested to enhance the silica dissolution rate. The specific surface area was identified as the main parameter controlling the rate of dissolution of the different silica particles studied, while particle size influences were minor. The dissolution of mesoporous silicas with different particle sizes has been studied in four different physiological buffers.

Molecular dynamics simulation of helium diffusion in vitreous silica

The helium diffusion through the non-porous vitreous silica was simulated by the molecular dynamics (MD) method. Truncated Morse potential was used to create models of vitreous silica. It was found that the quality of the simulation has been determined by the two main factors: the correct model of matrix in terms of the interstitial space geometry, and the quality of the gas-matrix interaction potential parameterization. The density of silica glass was in a good accordance with the experimental value 2.2g/cm3. The helium-silica interaction potential's parameterization has been done as close as possible to the conditions of a real migration of helium through the doorways connecting adjacent solubility sites. Taking into account of these two factors has allowed simulating the diffusion of helium through vitreous silica by molecular dynamics simulation quantitatively and calculating the diffusion coefficients which are close to the experimental values available in the literature.

Nanoporous aerogel as a bacteria repelling hygienic material for healthcare environment

Healthcare-associated infections (HAIs) caused by pathogenic bacteria are a worldwide problem and responsible for numerous cases of morbidity and mortality. Exogenous cross-contamination is one of the main mechanisms contributing to such infections. This work investigates the potential of hydrophobically modified nanoporous silica aerogel as an antiadhesive hygienic material that can inhibit exogenous bacterial contamination. Nanoporous silica aerogels were synthesized via sol–gel polymerization of tetraethyl orthosilicate and hydrophobized using trimethylsilyl chloride. Bacterial adhesion characteristics were evaluated via dip-inoculation in suspensions of Gram-negative Escherichia coli O157:H7 and Gram-positive Staphylococcus aureus. The attachment of E. coli O157:H7 and S. aureus to hydrophobic nanoporous silica aerogel (HNSA) was found to be significantly lower than that to hydrophilic and hydrophobic nonporous silica materials: 99.91% (E. coli O157:H7) and 99.93% (S. aureus) reduction in comparison to hydrophilic nonporous silica, and 82.95% (E. coli O157:H7) and 84.90% (S. aureus) reduction in comparison to hydrophobic nonporous silica. These results suggest that the use of HNSA as surfaces that come into contact with bacterial pathogens in the healthcare environment can improve bacterial hygiene, and therefore may reduce the rate of HAIs.