The Methyl Functionality of Monolithic Silica Xerogels Synthesized via the Co-Gelation Approach Combined with Surface Silylation.

The present research aims to investigate the chemical and morphological properties of the methylated silica xerogels produced via the co-gelation approach combined with surface silylation. In the sol−gel synthesis, methyltrimethoxysilane (MTMS) and tetraethylorthosilicate (TEOS) were utilized as silica precursors and trimethylchlorosilane (TMCS) served as a silylating agent. Structural changes were observed depending on the MTMS/TEOS molar ratio and on the post-synthesis-performed surface silylation of the xerogels. Post-synthesis silylation plays a critical role in the exchanging of the surface silanols with methyl groups, preserving the monolithic form. The morphological and structural changes were followed by SEM, 29Si-MAS-NMR, FTIR spectroscopy, nitrogen porosimetry, and contact angle measurements. The results have shown significant structural variations depending especially on the MTMS content. With an increasing MTMS content, the morphology of the samples has changed from a micro/mesoporous texture to a meso/macroporous texture. A higher degree of methyl substitution has been achieved for the silylated samples both confirmed by the FTIR and 29Si-NMR results. On the other hand, only the samples with a high MTMS content could preserve their structural integrity after evaporative drying, and all have exhibited a high degree of hydrophobicity with θ > 140°.

Physicochemical Characterization and Drug Release Properties of Methyl-Substituted Silica Xerogels Made Using Sol-Gel Process.

In this work, a multi-analytical approach involving nitrogen porosimetry, small angle neutron and X-ray scattering, Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, X-ray diffraction, thermal analysis and electron microscopy was applied to organically modified silica-based xerogels obtained through the sol-gel process. Starting from a tetraethoxysilane (TEOS) precursor, methyltriethoxysilane (MTES) was added to the reaction mixture at two different pH values (2.0 and 4.5) producing hybrid xerogels with different TEOS/MTES molar ratios. Significant differences in the structure were revealed in terms of the chemical composition of the silica network, hydrophilic/hydrophobic profile, particle dimension, pore shape/size and surface characteristics. The combined use of structural characterization methods allowed us to reveal a relation between the cavity dimensions, the synthesis pH value and the grade of methyl substitution. The effect of the structural properties on the controlled Captopril release efficiency has also been tested. This knowledge facilitates tailoring the pore network for specific usage in biological/medical applications. Knowledge on structural aspects, as reported in this work, represents a key starting point for the production of high-performance silica-based hybrid materials showing enhanced efficacy compared to bare silica prepared using only TEOS.

Hybrid Silica Materials Applied for Fuchsine B Color Removal from Wastewaters.

Hybrid materials, with applications in fuchsine B color removal from wastewaters, were obtained by in situ incorporation of platinum nanoparticles and/or Pt-porphyrin derivatives into silica matrices. The inorganic silica matrices were synthesized by the sol-gel method, conducted in acid-base catalysis in two steps and further characterized by Nitrogen porosimetry, Small Angle Neutron Scattering (SANS), Scanning electron microscopy, Atomic force microscopy and UV-vis spectroscopy. All of the investigated silica hybrid materials were 100% efficient in removing fuchsine B if concentrations were lower than 1 × 10-5 M. For higher concentrations, the silica matrices containing platinum, either modified with Pt-metalloporphyrin or with platinum nanoparticles (PtNPs), are the most efficient materials for fuchsine B adsorption from wastewaters. It can be concluded that the presence of the platinum facilitates chemical interactions with the dye molecule through its amine functional groups. An excellent performance of 197.28 mg fuchsine B/g adsorbent material, in good agreement with the best values mentioned in literature, was achieved by PtNPs-silica material, capable of removing the dye from solutions of 5 × 10-4 M, even in still conditions.

Mechanism of Hydration and Hydration Induced Structural Changes of Calcium Alginate Aerogel.

The most relevant properties of polysaccharide aerogels in practical applications are determined by their microstructures. Hydration has a dominant role in altering the microstructures of these hydrophilic porous materials. To understand the hydration induced structural changes of monolithic Ca-alginate aerogel, produced by drying fully cross-linked gels with supercritical CO2, the aerogel was gradually hydrated and characterized at different states of hydration by small-angle neutron scattering (SANS), liquid-state nuclear magnetic resonance (NMR) spectroscopy, and magic angle spinning (MAS) NMR spectroscopy. First, the incorporation of structural water and the formation of an extensive hydration sphere mobilize the Ca-alginate macromolecules and induce the rearrangement of the dry-state tertiary and quaternary structures. The primary fibrils of the original aerogel backbone form hydrated fibers and fascicles, resulting in the significant increase of pore size, the smoothing of the nanostructured surface, and the increase of the fractal dimension of the matrix. Because of the formation of these new superstructures in the hydrated backbone, the stiffness and the compressive strength of the aerogel significantly increase compared to its dry-state properties. Further elevation of the water content of the aerogel results in a critical hydration state. The Ca-alginate fibers of the backbone disintegrate into well-hydrated chains, which eventually form a quasi-homogeneous hydrogel-like network. Consequently, the porous structure collapses and the well-defined solid backbone ceases to exist. Even in this hydrogel-like state, the macroscopic integrity of the Ca-alginate monolith is intact. The postulated mechanism accounts for the modification of the macroscopic properties of Ca-alginate aerogel in relation to both humid and aqueous environments.

Design and Assessment of a Polyurethane Carrier Used for the Transmembrane Transfer of Acyclovir.

THE Herpes simplex viruses (HSV-1, HSV-2) are responsible for a wide variety of conditions, from cutaneous-mucosal to central nervous system (CNS) infections and occasional infections of the visceral organs, some of them with a lethal end. Acyclovir is often used intravenously, orally, or locally to treat herpetic infections but it must be administered with caution to patients with kidney disease and to children of early age. The main objectives of this study were to synthesize and evaluate new polyurethane nanoparticles that might be used as proper transmembrane carriers for acyclovir. Polyurethane particles were obtained by a polyaddition process: a mixture of two aliphatic diisocyanates used as organic phase was added to a mixture of butanediol and polyethylene glycol used as aqueous phase. Two different samples (with and without acyclovir, respectively) were synthesized and characterized by UV-Vis spectra in order to assess the encapsulation efficacy and the release profile, FT-IR, DSC, SEM, and SANS for structural characterization, as well as skin irritation tests. Nearly homogeneous samples with particle sizes between 78 and 91 nm have been prepared and characterized revealing a medium tendency to form clusters and a high resistance to heat up to 300 °C. The release profile of these nanoparticles is characteristic to a drug delivery system with a late discharge of the loaded active agents. Very slight increases in the level of transepidermal water loss and erythema were found in a 15-day evaluation on human skin. The results suggest the synthesis of a non-irritative carrier with a high encapsulation efficacy that can be successfully used for the transmembrane transfer of acyclovir.

Obtaining and Characterization of a Polydisperse System Used as a Transmembrane Carrier for Isosorbide Derivatives.

Due to their effect of vasodilatation, isosorbide nitrates represent one of the most important and most used solutions for angina pectoris. Unfortunately, these compounds have multiple dose-related adverse drug reactions such as headache, weakness, mild dizziness, and occasionally heart rate changes, nausea, vomiting, and sweating. The main aims of this research were to obtain and to evaluate new polyurethane (PU) structures that can be used as a proper transmembrane carrier with an improved release kinetic. Chitosan-based PU structures were obtained by a polyaddition process between hexamethylene diisocyanate and a mixture of chitosan, butanediol, and polyethylene glycol in the presence of caffeine as a synthesis catalyst. The obtained samples (with and without isosorbide nitrates) were characterized regarding the encapsulation and release rate (UV-Vis spectra), chemical composition (FTIR), thermal stability (thermal analysis), morphology changes (SEM and SANS), and in vivo irritation tests. These methods revealed no significant differences between the two sample structures. Multipopulational structures with sizes between 73 and 310 nm, with an increased tendency to form clusters and a high resistance to heat (up to 280°C), were obtained. This study presents an alternative administration of isosorbide derivatives based on a PU carrier with a high biocompatibility and a prolonged release.

SiO2-PVA-Fe(acac)3 Hybrid Based Superparamagnetic Nanocomposites for Nanomedicine: Morpho-textural Evaluation and In Vitro Cytotoxicity Assay.

A facile sol-gel route has been applied to synthesize hybrid silica-PVA-iron oxide nanocomposite materials. A step-by-step calcination (processing temperatures up to 400 °C) was applied in order to oxidize the organics together with the iron precursor. Transmission electron microscopy, X-ray diffraction, small angle neutron scattering, and nitrogen porosimetry were used to determine the temperature-induced morpho-textural modifications. In vitro cytotoxicity assay was conducted by monitoring the cell viability by the means of MTT assay to qualify the materials as MRI contrast agents or as drug carriers. Two cell lines were considered: the HaCaT (human keratinocyte cell line) and the A375 tumour cell line of human melanoma. Five concentrations of 10 µg/mL, 30 µg/mL, 50 µg/mL, 100 µg/mL, and 200 µg/mL were tested, while using DMSO (dimethylsulfoxid) and PBS (phosphate saline buffer) as solvents. The HaCaT and A375 cell lines were exposed to the prepared agent suspensions for 24 h. In the case of DMSO (dimethyl sulfoxide) suspensions, the effect on human keratinocytes migration and proliferation were also evaluated. The results indicate that only the concentrations of 100 µg/mL and 200 µg/mL of the nanocomposite in DMSO induced a slight decrease in the HaCaT cell viability. The PBS based in vitro assay showed that the nanocomposite did not present toxicity on the HaCaT cells, even at high doses (200 µg/mL agent).

Small-Angle Neutron Scattering Study of High Fat Fish Oil-In-Water Emulsion Stabilized with Sodium Caseinate and Phosphatidylcholine.

We report on small-angle neutron scattering (SANS) investigations of separate phase domains in high fat (70%) oil-in-water emulsions emulsified with the combination of sodium caseinate (CAS) and phosphatidylcholine (PC). The emulsion as a whole was studied by contrast variation to identify scattering components dominated by individual emulsifiers. The emulsion was subsequently separated into the aqueous phase and the oil-rich droplet phase, which were characterized separately. Emulsions produced with 1.05% (w/w) CAS and PC fraction which varies between 1.75% (w/w) and 0.35% (w/w) provided droplets between 10 and 19 µm in surface weighted mean in 70% fish oil-in-water emulsions. At least two-third of the overall CAS is associated with the interface, while the rest remains with the aqueous phase. Six percent of PC formed a monolayer in the interface, while the rest of the PC remains in the droplet phase in the form of multilayers. When the separated components were resuspended, the resuspended emulsion showed similar characteristics compared to the original emulsion in terms of droplet size distribution and neutron scattering. Instead, CAS in the aqueous phase separated from the emulsion shows aggregation not present in the corresponding CAS-in-D2O system.

Gelatin content governs hydration induced structural changes in silica-gelatin hybrid aerogels - Implications in drug delivery.

Silica-gelatin hybrid aerogels of varying gelatin content (from 4 wt.% to 24 wt.%) can be conveniently impregnated with hydrophobic active agents (e.g. ibuprofen, ketoprofen) in supercritical CO2 and used as drug delivery systems. Contrast variation neutron scattering (SANS) experiments show the molecular level hybridization of the silica and the gelatin components of the aerogel carriers. The active agents are amorphous, and homogeneously dispersed in these porous, hybrid matrices. Importantly, both fast and retarded drug release can be achieved with silica-gelatin hybrid aerogels, and the kinetics of drug release is governed by the gelatin content of the carrier. In this paper, for the first time, a molecular level explanation is given for the strong correlation between the composition and the functionality of a family of aerogel based drug delivery systems. Characterization of the wet aerogels by SANS and by NMR diffusiometry, cryoporometry and relaxometry revealed that the different hydration mechanisms of the aerogels are responsible for the broad spectrum of release kinetics. Low-gelatin (4-11 wt.%) aerogels retain their open-porous structure in water, thus rapid matrix erosion dictates fast drug release from these carriers. In contrast to this, wet aerogels of high gelatin content (18-24 wt.%) show well pronounced hydrogel-like characteristics, and a wide gradual transition zone forms in the solid-liquid interface. The extensive swelling of the high-gelatin hybrid backbone results in the collapse of the open porous structure, that limits mass transport towards the release medium, resulting in slower, diffusion controlled drug release. STATEMENT OF SIGNIFICANCE: Developing new drug delivery systems is a key aspect of pharmaceutical research. Supercritically dried mesoporous aerogels are ideal carriers for small molecular weight drugs due to their open porous structures and large specific surface areas. Hybrid silica-gelatin aerogels can display both fast and retarded drug release properties based on the gelatin contents of their backbones. The structural characterization of the aerogels by SANS and by NMR diffusiometry, cryoporometry and relaxometry revealed that the different hydration mechanisms of the hybrid backbones are responsible for the broad spectrum of release kinetics. The molecular level understanding of the functionality of these hybrid inorganic-biopolymer drug delivery systems facilitates the realization of quality-by-design in this research field.

Interfacial structure of 70% fish oil-in-water emulsions stabilized with combinations of sodium caseinate and phosphatidylcholine.

We report on the structural evaluation of high fat fish oil-in-water emulsions emulsified with sodium caseinate (CAS) and phosphatidylcholine (PC). The microemulsions contained 70% (w/w) fish oil with 1.05-1.4% (w/w) CAS and 0.4-1.75% (w/w) PC and were studied by the combination of light scattering together with small-angle X-ray and neutron scattering (SAXS/SANS). Aqueous CAS forms aggregates having a denser core of about 100 kDa and less dense shell about 400 kDa with the hard sphere diameter of 20.4 nm. PC appears as multilayers whose coherence length spans from 40 to 100 nm. PC monolayer separates oil and water phases. Moreover, 80% CAS particles are loosely bound to the interface but are not forming continuous coverage. The distance between aggregated CAS particles in microemulsion is increased compared to CAS aggregates in pure CAS-in-water system. PC multilayers become larger in the presence of oil-water interface compared to the pure PC mixtures. Bilayers become larger with increasing PC concentration. This study forms a structural base for the combination of CAS and PC emulsifiers forming a well-defined thin and dense PC layer together with thick but less dense CAS layer, which is assumed to explain its better oxidative stability compared to single emulsifiers.

Synthesis and characterization of a polyurethane carrier used for a prolonged transmembrane transfer of a chili pepper extract.

PURPOSE: Red chili peppers have been highly valued in gastronomy and traditional medicine since ancient times; it seems that it is not just an ingredient for food but also a good remedy for various medical conditions such as increased blood pressure and high levels of serum triglycerides and cholesterol, myocardial infarction, arthritis, and migraines. The objective of this study is the characterization of a new carrier used for encapsulated extract. METHODS: Chili pepper extract was obtained and was physically entrapped inside polyurethane microparticles in order to diminish the irritative potential of this extract. The particles were evaluated by Zetasizer measurements, small-angle neutron scattering and thermal analysis, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy; the encapsulation efficacy and the drug release profile were assessed by UV-Vis spectroscopy. Bioevaluations on mice skin were performed to predict the irritative potential of the samples. RESULTS: Two different types of samples were compared: hollow polyurethane microparticles vs polyurethane particles containing the natural extract. The sizes of the particles were very similar, but the sample containing the extract presents three particle populations (the polydispersity index increases from 0.3 to 0.6 from one sample to another). The zeta-potential measurements and SEM images indicate a medium tendency to form clusters, while the UV-Vis study revealed an almost 70% encapsulation efficacy. CONCLUSION: The results suggest that encapsulation of a chili pepper extract inside polyurethane microparticles leads to a non-irritative product with a prolonged release: ~30% of encapsulated extract is released within the first 8 days and a maximum 45% is reached in 2 weeks.

Improved Optical and Morphological Properties of Vinyl-Substituted Hybrid Silica Materials Incorporating a Zn-Metalloporphyrin.

This work is focused on a novel class of hybrid materials exhibiting enhanced optical properties and high surface areas that combine the morphology offered by the vinyl substituted silica host, and the excellent absorption and emission properties of 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin-Zn(II) tetrachloride as a water soluble guest molecule. In order to optimize the synthesis procedure and the performance of the immobilized porphyrin, silica precursor mixtures of different compositions were used. To achieve the requirements regarding the hydrophobicity and the porous structure of the gels for the successful incorporation of porphyrin, the content of vinyltriacetoxysilane was systematically changed and thoroughly investigated. Substitution of the silica gels with organic groups is a viable way to provide new properties to the support. An exhaustive characterization of the synthesized silica samples was realised by complementary physicochemical methods, such as infrared spectroscopy (FT-IR), absorption spectroscopy (UV-Vis) and photoluminescence, nuclear magnetic resonance spectroscopy (29Si-MAS-NMR) transmission and scanning electron microscopy (TEM and SEM), nitrogen absorption (BET), contact angle (CA), small angle X ray and neutron scattering (SAXS and SANS). All hybrids showed an increase in emission intensity in the wide region from 575 to 725 nm (Q bands) in comparison with bare porphyrin. By simply tuning the vinyltriacetoxysilane content, the hydrophilic/hydrophobic profile of the hybrid materials was changed, while maintaining a high surface area. Good control of hydrophobicity is important to enhance properties such as dispersion, stability behaviour, and resistance to water, in order to achieve highly dispersible systems in water for biomedical applications.

Association of Enterococcus cecorum with vertebral osteomyelitis and spondylolisthesis in broiler parent chicks.

Enterococcus cecorum is the most frequently occurring enterococcal species in the intestine of chickens of over 12 weeks of age, and there are few reports on its isolation from the skeleton of broiler parent chicks. In the present study, observations on vertebral osteomyelitis and spondylolisthesis ('kinky back syndrome') showing high incidence in 8 broiler parent flocks in different parts of Hungary are summarised. Clinical signs were seen only in roosters between 5 and 13 weeks of age. Diseased birds were alert and remained sitting on their hocks with their feet slightly raised off the ground. Incidence of the disease among male birds ranged from 8% to 30% depending on flocks. Enlargement and distortion of the body of the 6th vertebra were seen as the main pathological lesions. The cavity of the spinal canal was constricted by the distorted vertebral bodies. Resorption of bone tissue and sequestrum formation, signs of increased osteoclast activity, proliferation of fibrotic tissues, infiltration with heterophils and formation of sclerotic layers were detected in the vertebral bodies. From all 24 samples collected from the vertebral lesions, Enterococcus cecorum was isolated and identified using metabolic fingerprinting as well as 16S rRNA gene sequencing. Demonstration of E. cecorum from the vertebral lesions in all examined broiler breeder roosters showing the same clinical and pathological findings in different flocks suggested the pathogenic role of this microorganism for the first time in Hungary.