Anisotropic atomic layer deposition profiles of TiO₂ in hierarchical silica material with multiple porosity

Anisotropic deposition profiles of TiO2 in Zeotile-4 ordered mesoporous silica material are obtained using Atomic Layer Deposition (ALD) involving alternating pulses of tetrakis(dimethylamino) titanium (TDMAT) and water. TiO2 concentration profiles visualized by transmission electron microscopy (TEM) on particle cross sections reveal the systematic deeper penetration of the deposition front along the main channels and the more limited penetration in the perpendicular direction through the narrower slit-like mesopores. In ordered mesoporous material with one-dimensional pore system ALD leads to pore plugging. Diffusion limited ALD is shown to be useful for TiO2 deposition in anisotropic mesoporous support materials

Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica

This study aims to evaluate the in vivo performance of ordered mesoporous silica (OMS) as a carrier for poorly water soluble drugs. Itraconazole was selected as model compound. Physicochemical characterization was carried out by SEM, TEM, nitrogen adsorption, DSC, TGA and in vitro dissolution. After loading itraconazole into OMS, its oral bioavailability was compared with the crystalline drug and the marketed product Sporanox® in rabbits and dogs. Plasma concentrations of itraconazole and OH-itraconazole were determined by HPLC-UV. After administration of crystalline itraconazole in dogs (20 mg), no systemic itraconazole could be detected. Using OMS as a carrier, the AUC₀-₈ was boosted to 681 ± 566 nM h. In rabbits, the AUC₀-₂₄ increased significantly from 521 ± 159 nM h after oral administration of crystalline itraconazole (8 mg) to 1069 ± 278 nM h when this dose was loaded into OMS. Tmax decreased from 9.8 ± 1.8 to 4.2 ± 1.8 h. No significant differences (AUC, Cmax, and Tmax) could be determined when comparing OMS with Sporanox® in both species. The oral bioavailability of itraconazole formulated with OMS as a carrier compares well with the marketed product Sporanox®, in rabbits as well as in dogs. OMS can therefore be considered as a promising carrier to achieve enhanced oral bioavailability for drugs with extremely low water solubility.status: publishe

Binary phase diagram of tetraethyl orthosilicate and carbon dioxide

Phase equilibrium data for the system tetraethyl orthosilicate (TEOS)-carbon dioxide (CO2) are presented. The measurements were conducted in a variable volume phase monitoring cell at different temperatures (306.2, 313.2, 323.2, 333.2, and 343.2) K. The mole fraction of TEOS in the binary mixture was varied from 0.00 to 0.08. The data were fitted using the Peng-Robinson equation of state. The model accounts for literature data on phase behavior over the entire composition range. © 2008 American Chemical Society.status: publishe

Physical state of poorly water soluble therapeutic molecules loaded into SBA-15 ordered mesoporous silica carriers: a case study with itraconazole and ibuprofen

The ordered mesoporous silica material SBA-15 was loaded with the model drugs itraconazole and ibuprofen using three different procedures: (i) adsorption from solution, (ii) incipient wetness impregnation, and (iii) heating of a mixture of drug and SBA-15 powder. The location of the drug molecules in the SBA-15 particles and molecular interactions were investigated using nitrogen adsorption, TGA, DSC, DRS UV−vis, and XPS. The in vitro release of hydrophobic model drugs was evaluated in an aqueous environment simulating gastric fluid. The effectiveness of the loading method was found to be strongly compound dependent. Incipient wetness impregnation using a concentrated itraconazole solution in dichloromethane followed by solvent evaporation was most efficient for dispersing itraconazole in SBA-15. The itraconazole molecules were located on the mesopore walls and inside micropores of the mesopore walls. When SBA-15 was loaded by slurrying it in a diluted itraconazole solution from which the solvent was evaporated, the itraconazole molecules ended up in the mesopores that they plugged locally. At a loading of 30 wt %, itraconazole exhibited intermolecular interactions inside the mesopores revealed by UV spectroscopy and endothermic events traced with DSC. The physical mixing of itraconazole and SBA-15 powder followed by heating above the itraconazole melting temperature resulted in formulations in which glassy itraconazole particles were deposited externally on the SBA-15 particles. Loading with ibuprofen was successful with each of the three loading procedures. Ibuprofen preferably is positioned inside the micropores. In vitro release experiments showed fast release kinetics provided the drug molecules were evenly deposited over the mesoporous surface.status: publishe

Investigation of the cytotoxicity of nanozeolites A and Y

Nanosized zeolite particles are important materials for many applications in the field of nanotechnology. The possible adverse effects of these nanomaterials on human health have been scarcely investigated and remain largely unknown. This study reports the synthesis of nanozeolites Y and A with particle sizes of 25-100 nm and adequate colloidal stability for in vitro cytotoxicity experiments. The cytotoxic response of macrophages, epithelial and endothelial cells to these nanocrystals was assessed by determining mitochondrial activity (MTT assay) and cell membrane integrity (LDH leakage assay). After 24 h of exposure, no significant cytotoxic activity was detected for nanozeolite doses up to 500 μg/ml. The addition of fetal calf serum to the cell culture medium during exposure did not significantly change this low response. The nanozeolites showed low toxicity compared with monodisperse amorphous silica nanoparticles of similar size (60 nm). These results may contribute to the application of safe nanozeolites for purposes such as medical imaging, sensing materials, low-k films and molecular separation processes.status: publishe

Molecular organization of hydrophobic molecules and co-adsorbed water in SBA-15 ordered mesoporous silica material

The purpose of this study was to improve our understanding of the molecular organization of hydrophobic guest molecules in the presence of co-adsorbed water inside SBA-15 ordered mesoporous silica material. Understanding this adsorption competition is essential in the development of applications of controlled adsorption and desorption. The poorly water soluble drug compound itraconazole and the fluorescent probe Nile red were selected for the study. The interaction between itraconazole and SBA-15 was investigated using FT-IR, H-1 MAS NMR and Si-29 MAS NMR spectroscopy, by determination of adsorption isotherms and release kinetics in simulated gastric fluid. The distribution and migration of the hydrophobic fluorescent probe Nile red was visualized in situ using confocal fluorescence microscopy. For both molecules, there was a pronounced influence of the co-adsorbed water on adsorption, hydrophobic aggregation and migration in SBA-15 pores. These insights contribute to the development of practical methods for loading ordered mesoporous silica materials with hydrophobic molecules.status: publishe

Investigation of the cytotoxicity of nanozeolites A and Y.

Nanosized zeolite particles are important materials for many applications in the field of nanotechnology. The possible adverse effects of these nanomaterials on human health have been scarcely investigated and remain largely unknown. This study reports the synthesis of nanozeolites Y and A with particle sizes of 25-100 nm and adequate colloidal stability for in vitro cytotoxicity experiments. The cytotoxic response of macrophages, epithelial and endothelial cells to these nanocrystals was assessed by determining mitochondrial activity (MTT assay) and cell membrane integrity (LDH leakage assay). After 24 h of exposure, no significant cytotoxic activity was detected for nanozeolite doses up to 500 μg/ml. The addition of fetal calf serum to the cell culture medium during exposure did not significantly change this low response. The nanozeolites showed low toxicity compared with monodisperse amorphous silica nanoparticles of similar size (60 nm). These results may contribute to the application of safe nanozeolites for purposes such as medical imaging, sensing materials, low-k films and molecular separation processes

Single-step alcohol-free synthesis of core-shell nanoparticles of beta-casein micelles and silica

A new, single-step protocol for wrapping individual nanosized β-casein micelles with silica is presented. This biomolecule-friendly synthesis proceeds at low protein concentration at almost neutral pH, and makes use of sodium silicate instead of the common silicon alkoxides. This way, formation of potentially protein-denaturizing alcohols can be avoided. The pH of the citrate-buffered synthesis medium is close to the isoelectric point of β-casein, which favours micelle formation. A limited amount of sodium silicate is added to the protein micelle suspension, to form a thin silica coating around the β-casein micelles. The size distribution of the resulting protein-silica structures was characterized using DLS and SAXS, as well as 1H NMR DOSY with a dedicated pulsed-field gradient cryo-probehead to cope with the low protein concentration. The degree of silica-condensation was investigated by 29Si MAS NMR, and the nanostructure was revealed by advanced electron microscopy techniques such as ESEM and HAADF-STEM. As indicated by the combined characterization results, a silica shell of 2 nm is formed around individual β-casein micelles giving rise to separate protein core-silica shell nanoparticles of 17 nm diameter. This alcohol-free method at mild temperature and pH is potentially suited for packing protein molecules into bio-compatible silica nanocapsules for a variety of applications in biosensing, therapeutic protein delivery and biocatalysis. © the Partner Organisations 2014.status: publishe