Influence of PEG Chain Length of Functionalized Magnetic Nanoparticles on the Cytocompatibility and Immune Competence of Primary Murine Macrophages and Dendritic Cells.

A major drawback of nanoparticles (NPs) for biomedical applications is their preferential phagocytosis in immune cells, which can be avoided by surface modifications like PEGylation. Nevertheless, examinations of different polyethylene glycol (PEG) chain lengths on the competence of immune cells as well as possible immunotoxic effects are still sparse. Therefore, primary murine macrophages and dendritic cells were generated and incubated with magnetic nanoporous silica nanoparticles (MNPSNPs) modified with different mPEG chains (2 kDa, 5 kDa, and 10 kDa). Cytotoxicity, cytokine release, and the formation of reactive oxygen species (ROS) were determined. Immune competence of both cell types was examined and uptake of MNPSNPs into macrophages was visualized. Concentrations up to 150 µg/mL MNPSNPs showed no effects on the metabolic activity or immune competence of both cell types. However, ROS significantly increased in macrophages incubated with larger PEG chains, while the concentration of cytokines (TNF-α and IL-6) did not indicate a proinflammatory process. Investigations on the uptake of MNPSNPs revealed no differences in the onset of internalization and the intensity of intracellular fluorescence. The study gives no indication for an immunotoxic effect of PEGylated MNPSNPs. Nevertheless, there is still a need for optimization regarding their internalization to ensure an efficient drug delivery.

Sponge-liked Silica Nanoporous Particles for Sustaining Release and Long-Term Antibacterial Activity of Natural Essential Oil.

To improve the sustained release and long-term antibacterial activity of Chimonanthus nitens Oliv. essential oil (CEO), novel sponge-liked nanoporous silica particles (SNP) were synthesized via the soft template method, which was employed as a biocompatible carrier to prepare spong-liked nanoporous silica particles loading with CEO (CEO-SNP) through physical adsorption. The structure and properties of the samples were characterized via N2 adsorption/desorption measurements, thermogravimetry (TGA), Fourier transform infrared, SEM and TEM. The result showed that the SNP exhibited an excellent loading capability of CEO up to 76.3%. The thermal stability and release behavior of the CEO were significantly improved via the physical adsorption of the SNP materials. The release profile of CEO was in accordance with the first-order kinetic model, which meant that the release mechanism was drug Fick's diffusion. The antibacterial evaluation results demonstrated that the CEO-SNP exhibited strong antibacterial activity against S. aureus, E. coli and P. aeruginosa. The antibacterial results have shown that the CEO-SNP could destroy the cell structure of bacteria, and result in the generation of oxidative stress and the release of nucleic acid. After storage of 30 d at 25 °C, the CEO-SNP still had the stronger antibacterial activity towards S. aureus, E. coli and P. aeruginosa in comparison with CEO. Therefore, the sponge-like silica nanoporous particles seemed to be a promising carrier for long-term stability and antibacterial delivery of CEO.

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics.

BACKGROUND: In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology. RESULTS: Clinical and histological examinations showed no MNPSNP-associated changes in mice at all investigated time points. Although PEGylated, MNPSNPs were mainly trapped in lung, liver, and spleen. Over time, they showed two distributional patterns: early significant drops in blood, lung, and kidney and slow decreases in liver and spleen. The accumulation of MNPSNPs on the magnetizable implant and in its area was very low with no significant differences towards the control. CONCLUSION: Despite massive nanoparticle capture by the mononuclear phagocyte system, no significant pathomorphological alterations were found in affected organs. This shows good biocompatibility of MNPSNPs after intravenous administration. The organ uptake led to insufficient availability of MNPSNPs in the implant region. For that reason, among others, the nanoparticles did not achieve targeted accumulation in the desired way, manifesting future research need. However, with different conditions and dimensions in humans and further modifications of the nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason.

In vitro and in vivo accumulation of magnetic nanoporous silica nanoparticles on implant materials with different magnetic properties.

BACKGROUND: In orthopedic surgery, implant-associated infections are still a major problem. For the improvement of the selective therapy in the infection area, magnetic nanoparticles as drug carriers are promising when used in combination with magnetizable implants and an externally applied magnetic field. These implants principally increase the strength of the magnetic field resulting in an enhanced accumulation of the drug loaded particles in the target area and therewith a reduction of the needed amount and the risk of undesirable side effects. In the present study magnetic nanoporous silica core-shell nanoparticles, modified with fluorophores (fluorescein isothiocyanate/FITC or rhodamine B isothiocyanate/RITC) and poly(ethylene glycol) (PEG), were used in combination with metallic plates of different magnetic properties and with a magnetic field. In vitro and in vivo experiments were performed to investigate particle accumulation and retention and their biocompatibility. RESULTS: Spherical magnetic silica core-shell nanoparticles with reproducible superparamagnetic behavior and high porosity were synthesized. Based on in vitro proliferation and viability tests the modification with organic fluorophores and PEG led to highly biocompatible fluorescent particles, and good dispersibility. In a circular tube system martensitic steel 1.4112 showed superior accumulation and retention of the magnetic particles in comparison to ferritic steel 1.4521 and a Ti90Al6V4 control. In vivo tests in a mouse model where the nanoparticles were injected subcutaneously showed the good biocompatibility of the magnetic silica nanoparticles and their accumulation on the surface of a metallic plate, which had been implanted before, and in the surrounding tissue. CONCLUSION: With their superparamagnetic properties and their high porosity, multifunctional magnetic nanoporous silica nanoparticles are ideal candidates as drug carriers. In combination with their good biocompatibility in vitro, they have ideal properties for an implant directed magnetic drug targeting. Missing adverse clinical and histological effects proved the good biocompatibility in vivo. Accumulation and retention of the nanoparticles could be influenced by the magnetic properties of the implanted plates; a remanent martensitic steel plate significantly improved both values in vitro. Therefore, the use of magnetizable implant materials in combination with the magnetic nanoparticles has promising potential for the selective treatment of implant-associated infections.

Isatin functionalized nanoporous SBA-15 as a selective fluorescent probe for the detection of Hg(II) in water.

A highly ordered mesoporous silica material functionalized with isatin (SBA-Pr-IS) was designed and synthesized. Characterization techniques including XRD, TGA, BET, SEM, and FT-IR were employed to characterize the pore structure, textural properties, microscopic morphology, and molecular composition of grafted organic moieties of SBA-Pr-IS. The successful attachment of the organic moiety (0.34 mmol g-1) without the SBA-15 structure collapsing after the modification steps was confirmed. Fluorescence characterization of SBA-Pr-IS was examined upon addition of a wide variety of cations in aqueous medium and it showed high sensitivity toward Hg2+ ions. During testing in an ion competition experiment, it was observed that the fluorescence changes of the probe were remarkably specific for Hg2+ ions. Furthermore, a good linearity between the fluorescence intensity of this material and the concentration of Hg2+ ions was constructed with a suitable detection limit of 3.7 × 10-6 M. Finally, the applicability of the proposed method was successfully evaluated for the determination of Hg2+ ions in real samples. Therefore, SBA-Pr-IS can be used as an efficient fluorescence probe for Hg2+ ions. Graphical Abstract A novel organic-inorganic hybrid material was designed and synthesized by functionalization of SBA-15 mesoporous silica material with isatin. The evaluation of the sensing ability of SBA-Pr-IS using fluorescence spectroscopy revealed that the SBA-Pr-IS was a selective fluorescent probe for Hg2+ ion in water in the presence of a wide range of metal cations.

Analysis of formaldehyde and acrolein in the aqueous samples using a novel needle trap device containing nanoporous silica aerogel sorbent.

In this research, a needle trap device (NTD) packed with nanoporous silica aerogel as a sorbent was used as a new technique for sampling and analysis of formaldehyde and acrolein compounds in aqueous and urine samples. The obtained results were compared with those of the commercial sorbent Carboxen1000. Active sampling was used and a 21-G needle was applied for extraction of gas in the sample headspace. The optimization of experimental parameters like salt addition, temperature and desorption time was done and the performance of the NTD for the extraction of the compounds was evaluated. The optimum temperature and time of desorption were 280 °C and 2 min, respectively. The ranges of limit of detection, limit of quantification and relative standard deviation (RSD) were 0.01-0.03 µg L-1, 0.03-0.1 µg L-1 and 2.8-7.3%, respectively. It was found that the NTD containing nanoporous silica aerogel had a better performance. Thus, this technique can be applied as an effective and reliable method for sampling and analysis of aldehyde compounds from different biological matrices like urine, exhalation and so on.

A Novel Naphthalene-Immobilized Nanoporous SBA-15 as a Highly Selective Optical Sensor for Detection of Fe(3+) in Water.

A novel organic-inorganic hybrid optical sensor (SBA-NCO) was designed and synthesized through immobilization of isocyanatopropyl-triethoxysilane and 1-amino-naphthalene onto the surface of SBA-15 by post-grafting method. The characterization of materials using XRD, TEM, N2 adsorption-desorption, and FT-IR techniques confirmed the successful attachment of organic moieties and preserving original structure of SBA-15 after modification step. Fluorescence experiments demonstrated that SBA-NCO was a highly selective optical sensor for the detection of Fe(3+) directly in water over a wide range of metal cations including Na(+), Mg(2+), Al(3+), K(+), Ca(2+), Cr(3+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+) in a wide pH values.

Nanopore film based enrichment and quantification of low abundance hepcidin from human bodily fluids.

Endogenous peptides that represent biological and pathological information of disease have attracted interest for diagnosis. However, the extraction of those low abundance peptides is still a challenge because of the complexity of human bodily fluids (HBF). Hepcidin, a peptide hormone, has been recognized as a biomarker for iron-related diseases. There is no rapid and reliable way to enrich them from HBF. Here we describe a peptide extraction approach based on nanoporous silica thin films to successfully detect hepcidin from HBF. Cooperative functions of nanopore to biomolecule, including capillary adsorption, size-exclusion and electrostatic interaction, were systematically investigated to immobilize the target peptide. To promote this new approach to clinical practices, we further applied it to successfully assay the hepcidin levels in HBF provided by healthy volunteers and patients suffering from inflammation. Our finding provides a high-throughput, rapid, label-free and cost-effective detection method for capturing and quantifying low abundance peptides from HBF. FROM THE CLINICAL EDITOR: Diagnosing diseases with low concentration peptide biomarkers remains challenging. This team of authors describes a peptide extraction approach based on nanoporous silica thin films to successfully detect low concentrations of hepcidin from human body fluids collected from 119 healthy volunteers and 19 inflammation patients.

Coumarin derivative-functionalized nanoporous silica as an on-off fluorescent sensor for detecting Fe3+ and Hg2+ ions: a circuit logic gate.

A highly efficient fluorescent sensor (S-DAC) was easily created by functionalizing the SBA-15 surface with N-(2-Aminoethyl)-3-Aminopropyltrimethoxysilane followed by the covalent attachment of 7-diethylamino 3-acetyl coumarin (DAC). This chemosensor (S-DAC) demonstrates selective and sensitive recognition of Fe3+ and Hg2+ in water-based solutions, with detection limits of 0.28 × 10-9 M and 0.2 × 10-9 M for Hg2+ and Fe3+, respectively. The sensor's fluorescence characteristics were examined in the presence of various metal ions, revealing a decrease in fluorescence intensity upon adding Fe3+ or Hg2+ ions at an emission wavelength of 400 nm. This sensor was also able to detect ferric and mercury ions in spinach and tuna fish. The quenching mechanism of S-DAC was investigated using UV-vis spectroscopy, which confirmed a static-type mechanism for fluorescence quenching. Moreovre, the decrease in fluorescence intensity caused by mercury and ferric ions can be reversed using trisodium citrate dihydrate and EDTA as masking agents, respectively. As a result, a circuit logic gate was designed using Hg2+, Fe3+, trisodium citrate dihydrate, and EDTA as inputs and the quenched fluorescence emission as the output.

Effective transport of aggregated hypericin encapsulated in SBA-15 nanoporous silica particles for photodynamic therapy of cancer cells.

Photodynamic therapy (PDT) represents an interesting modality for the elimination of damaged biomaterials and cells. This treatment takes advantage of the photosensitizing properties of molecules that are active only when irradiated with light. In the present work, a dual property of hypericin, a hydrophobic molecule with high performance in photodiagnostics and photodynamic therapy, was exploited. The non-fluorescent and photodynamically inactive form of hypericin aggregates was loaded into the nanopores of SBA-15 silica particles. The synthesized particles were characterized by infrared spectroscopy, thermogravimetry, differential thermal analysis, small-angle X-ray scattering and transmission electron microscopy. Hypericin aggregates were confirmed by absorption spectra typical of aggregated hypericin and by its short fluorescence lifetime. Release of hypericin from the particles was observed toward serum proteins, mimicking physiological conditions. Temperature- and time-dependent uptake of hypericin by cancer cells showed gradual release of hypericin from the particles and active cellular transport by endocytosis. A closer examination of SBA-15-hypericin uptake by fluorescence lifetime imaging showed that aggregated hypericin molecules, characterized by a short fluorescence lifetime (∼4 ns), were still present in the SBA-15 particles upon uptake by cells. However, monomerization of hypericin in cancer cells was observed by extending the hypericin fluorescence lifetime by ∼8 ns, preferentially in lipid compartments and the plasma membrane. This suggests a promising prognosis for delayed biological activity of the entire cargo, which was confirmed by effective PDT in vitro. In summary, this work presents an approach for safe, inactive delivery of hypericin that is activated at the target site in cells and tissues.

Low-field NMR investigations on dynamics of crude oil confined into nanoporous silica rods and white powder.

In the present study, to mimic the natural confinement of crude oils, model experiments are conducted with crude oils having different physical properties and maltenes of parent crude oils without asphaltenes confined into engineered nanoporous silica rods with pore diameters of 2.5 and 10.0 nm and white powdered nanoporous silica with pore diameters of 2.5 and 4.0 nm. This will help with suggesting potential treatments for enhancing crude oil recovery. Low-field nuclear magnetic resonance (LF-NMR) relaxometry has been applied to achieve this goal. The nanoporous proxies resemble real-life nanoporous rocks of reservoirs. The dynamics of confined crude oils with different oAPI gravity deviate from bulk dynamics, and deviation changes depending on the oAPI gravity. This suggests that treatments must be decided appropriately before crude oil production. Similar treatments could be applied for light and medium-heavy crude oils. Mathematical analysis of NMR relaxation curves of confined crude oils with different fractions of SARA (saturates, aromatics, resins, asphaltenes) indicates that the conventional SARA approach needs a better definition for the confined state of matter. The NMR relaxation behavior of confined maltenes shows that resin molecules might act like saturates in natural confinement with various scale pores from nano to micro and even macro, or aromatics might show resin-like behaviors. Confinement of brine and a light crude oil into white powdered nanoporous silica proxies demonstrates that brine could be utilized along with some additives such as nanoparticles for oil recovery. Therefore, these issues must be evaluated in deciding the proper treatments for crude oil production.

Development of Autopolymerizing Resin Material with Antimicrobial Properties Using Montmorillonite and Nanoporous Silica.

Although autopolymerizing resin offers numerous applications in orthodontic treatment, plaque tends to accumulate between the appliance and the mucosa, which increases the number of microorganisms present. In this study, we added cetylpyridinium chloride (CPC) loaded montmorillonite (Mont) and nanoporous silica (NPS) to autopolymerizing resin (resin-Mont, resin-NPS) and evaluated their drug release capacity, antimicrobial capacity, drug reuptake capacity, mechanical strength, and color tone for the devolvement of autopolymerizing resin with antimicrobial properties. As observed, resin-Mont and resin-NPS were capable of the sustained release of CPC for 14 d, and a higher amount of CPC was released compared to that of resin-CPC. Additionally, resin-Mont and resin-NPS could reuptake CPC. Moreover, the antimicrobial studies demonstrated that resin-Mont and resin-NPS could release effective amounts of CPC against Streptococcus mutans for 14 d and 7 d after reuptake, respectively. Compared to resin-CPC, resin-Mont exhibited a higher sustained release of CPC in all periods, both in the initial sustained release and after reuptake. However, the mechanical strength decreased with the addition of Mont and NPS, with a 36% reduction observed in flexural strength for resin-Mont and 25% for resin-NPS. The application of these results to the resin portion of the orthodontic appliances can prevent bacterial growth on the surface, as well as on the interior, of the appliances and mitigate the inflammation of the mucosa.

Surface Interactions and Nanoconfinement of Methane and Methane plus CO2 Revealed by High-Pressure Magic Angle Spinning NMR Spectroscopy and Molecular Dynamics.

This study explores the fundamental, molecular- to microscopic-level behavior of methane gas confined into nanoporous silica proxies with different pore diameters and surface-to-volume (S/V) ratios. Surfaces and pore walls of nanoporous silica matrices are decorated with hydroxyl (-OH) groups, resembling natural heterogeneity. High-pressure MAS NMR was utilized to characterize the interactions between methane and the engineered nanoporous silica proxies under various temperature and pressure regimes. There was a change in the chemical shift position of confined methane slightly in the mixtures with nanoporous silica up to 393 K, as shown by high-pressure 13C-NMR. The 13C-NMR chemical shift of methane was changed by pressure, explained by the densification of methane inside the nanoporous silica materials. The influence of pore diameter and S/V of the nanoporous silica materials on the behaviors and dynamics of methane were studied. The presence of CO2 in mixtures of silica and methane needs analysis with caution because CO2 in a supercritical state and gaseous CO2 change the original structure of nanoporous silica and change surface area and pore volume. According to simulation, the picosecond scale dynamics of methane confined in larger pores of amorphous silica is faster. In the 4 nm pore, the diffusivity obtained from MD simulations in the pore with a higher S/V ratio is slower due to the trapping of methane molecules in adsorbed layers close to the corrugated pore surface. In contrast, relaxation measured with NMR for smaller pores (higher S/V) exhibits larger T1, indicating slower relaxation.

Selective Detection of Volatile Organics in a Mixture Using a Photoionization Detector and Thermal Desorption from a Nanoporous Preconcentrator.

The selective detection of individual hazardous volatile organic compounds (VOCs) within a mixture is of great importance in industrial contexts due to environmental and health concerns. Achieving this with inexpensive, portable detectors continues to be a significant challenge. Here, a novel thermal separator system coupled with a photoionization detector has been developed, and its ability to selectively detect the VOCs isopropanol and 1-octene from a mixture of the two has been studied. The system includes a nanoporous silica preconcentrator in conjunction with a commercially available photoionization detector (PID). The PID is a broadband total VOC sensor with little selectivity; however, when used in conjunction with our thermal desorption approach, selective VOC detection within a mixture can be achieved. VOCs are adsorbed in the nanoporous silica over a 5 min period at 5 °C before being desorbed by heating at a fixed rate to 70 °C and detected by the PID. Different VOCs desorb at different times/temperatures, and mathematical analysis of the set of PID responses over time enabled the contributions from isopropanol and 1-octene to be separated. The concentrations of each compound individually could be measured in a mixture with limits of detection less than 10 ppbv and linearity errors less than 1%. Demonstration of a separation of a mixture of chemically similar compounds, benzene and o-xylene, is also provided.

Relating Mobility of dsRNA in Nanoporous Silica Particles to Loading and Release Behavior.

Nanoparticle delivery of polynucleic acids traditionally relies on the modulation of surface interactions to achieve loading and release. This work investigates the additional role of confinement in mobility of dsRNA (84 and 282 base pair (bp) sequences of Spodoptera frugiperda) as a function of silica nanopore size (nonporous, 3.9, 8.0, and 11.3 nm). Amine-functionalized nanoporous silica microspheres (NPSMs, ∼10 µm) are used to directly visualize the loading and exchange of fluorescently labeled dsRNA. Porous particles are fully accessible to both lengths of dsRNA by passive diffusion, except for 282 bp dsRNA in 3.9 nm pores. The stiffness of dsRNA suggests that encapsulation occurs by threading into nanopores, which is inhibited when the ratio of dsRNA length to pore size is large. The mobility of dsRNA at the surface and in the core of NPSMs, as measured by fluorescence recovery after photobleaching, is similar. The mobility increases with pore size (from 0.0002 to 0.001 µm2/s for 84 bp dsRNA in 3.9-11.3 nm pores) and decreases with the length of dsRNA. However, when the dsRNA is unable to load into the pores (on nonporous particles and for 282 bp dsRNA in 3.9 nm pores), surface mobility is not detectable. The pore structure appears to serve as a "source" to provide a mobile network of dsRNA at the particle surface. The importance of mobility is demonstrated by exchange experiments, where NPSMs saturated with mobile dsRNA can exchange dsRNA with the surrounding solution, while immobile dsRNA is not exchanged. These results indicate that nanoparticle synthesis techniques that provide pores large enough to take up polynucleic acids internally (and not simply on the external surface of the particle) can be harnessed to design polynucleic acid/nanoporous silica combinations for controlled mobility as a path forward toward effective nanocarriers.

Chemically induced hypoxia by dimethyloxalylglycine (DMOG)-loaded nanoporous silica nanoparticles supports endothelial tube formation by sustained VEGF release from adipose tissue-derived stem cells.

Inadequate vascularization leading to insufficient oxygen and nutrient supply in deeper layers of bioartificial tissues remains a limitation in current tissue engineering approaches to which pre-vascularization offers a promising solution. Hypoxia triggering pre-vascularization by enhanced vascular endothelial growth factor (VEGF) expression can be induced chemically by dimethyloxalylglycine (DMOG). Nanoporous silica nanoparticles (NPSNPs, or mesoporous silica nanoparticles, MSNs) enable sustained delivery of molecules and potentially release DMOG allowing a durable capillarization of a construct. Here we evaluated the effects of soluble DMOG and DMOG-loaded NPSNPs on VEGF secretion of adipose tissue-derived stem cells (ASC) and on tube formation by human umbilical vein endothelial cells (HUVEC)-ASC co-cultures. Repeated doses of 100 µM and 500 µM soluble DMOG on ASC resulted in 3- to 7-fold increased VEGF levels on day 9 (P < 0.0001). Same doses of DMOG-NPSNPs enhanced VEGF secretion 7.7-fold (P < 0.0001) which could be maintained until day 12 with 500 µM DMOG-NPSNPs. In fibrin-based tube formation assays, 100 µM DMOG-NPSNPs had inhibitory effects whereas 50 µM significantly increased tube length, area and number of junctions transiently for 4 days. Thus, DMOG-NPSNPs supported endothelial tube formation by upregulated VEGF secretion from ASC and thus display a promising tool for pre-vascularization of tissue-engineered constructs. Further studies will evaluate their effect in hydrogels under perfusion.

Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs.

This study aims to examine the contribution of nanoporous silica entrapped lipid-drug complexes (NSCs) in improving the solubility and bioavailability of dutasteride (DUT). An NSC was loaded with DUT (dissolved in lipids) and dispersed at a nanoscale level using an entrapment technique. NSC microemulsion formation was confirmed using a ternary phase diagram, while the presence of DUT and lipid entrapment in NSC was confirmed using scanning electron microscopy. Differential scanning calorimetry and X-ray diffraction revealed the amorphous properties of NSC. The prepared all NSC had excellent flowability and enhanced DUT solubility but showed no significant difference in drug content homogeneity. An increase in the lipid content of NSC led to an increase in the DUT solubility. Further the NSC were formulated as tablets using D-α tocopheryl polyethylene glycol 1000 succinate, glyceryl caprylate/caprate, and Neusilin®. The NSC tablets showed a high dissolution rate of 99.6% at 30 min. Furthermore, NSC stored for 4 weeks at 60 °C was stable during dissolution testing. Pharmacokinetic studies performed in beagle dogs revealed enhanced DUT bioavailability when administered as NSC tablets. NSC can be used as a platform to develop methods to overcome the technical and commercial limitations of lipid-based preparations of poorly soluble drugs.

Formation of Double-Helical Structures by Silica Nanotubes Templated by Mixtures of Common Nonionic Surfactants in Aqueous Solutions.

Micelles of Pluronic F108 (EO132PO50EO132)/P104 (EO27PO61EO27) surfactant mixtures swollen with toluene were found to template silica nanotubes that formed double-helical structures under appropriately selected aqueous acidic solution conditions. In particular, the double-helical nanotube structure (DHNTS) formed as a main product at 15 °C for 30-37.5 wt % of Pluronic P104 in a surfactant mixture, with 35 wt % being particularly suitable. The formation of DHNTSs appears to involve a spontaneous wrapping of micelle-templated nanotubes around one another, while a similar structure was known to form only under confinement of anodic alumina pores of appropriate diameter. In addition to DHNTSs, other helical or circular structures, such as a helical nanotube tightly wrapped around a straight nanotube, or nanotube(s) wrapped around a sphere, were observed in many cases as minor components. DHNTSs formed as a major component at a well-defined proportion of silica precursor to surfactant at 15 °C, while the relative amount of the swelling agent and the hydrochloric acid concentration could be varied considerably. The hydrothermal treatment temperature was used to adjust the pore diameter of the DHNTS. However, structures formed without the hydrothermal treatment or with the treatment at a moderate temperature appeared very soft, while the treatment at excessively high temperature resulted in a development of significant gaps in the nanotube walls. Our results establish DHNTS as a well-defined ordered mesoporous silica with ultralarge (∼35 nm) helical mesopores of some degree of diameter adjustability, accessible under aqueous conditions using common nonionic surfactants as templating agents.

Ion Capture and Release Ability of Glass Ionomer Cement Containing Nanoporous Silica Particles with Different Pore and Particle Size.

This study prepared glass ionomer cement (GIC) containing nanoporous silica (NPS) (GIC-NPS) at 5 wt% concentrations using 3 types of NPS with different pore and particle sizes and evaluated the differences in their cationic ion capture/release abilities and mechanical properties. The cationic water-soluble dye was used as cationic ion. The test GIC-NPS complexes captured dyes by immersion in 1 wt% dye solutions. All the GIC-NPS complexes released dyes for 28 d, and the amount of dye released from the complexes increased with decreasing pore size; however, the particle size of NPS did not affect the amount of dye released. Additionally, GIC-NPS was able to recharge the dye, and the amount of released the dye by the complexes after recharge was almost identical to the amount released on the first charge. Although not significantly different, the compressive strength of GIC-NPS was slightly greater than that of GIC without NPS regardless of the type of NPS. These results suggest that the degree of capture and release of cationic molecules, such as drugs, can be controlled by optimizing the pore size of NPS without sacrificing its mechanical strength when its content is 5 wt%.

Calcium Charge and Release of Conventional Glass-Ionomer Cement Containing Nanoporous Silica.

The aim of this study was to evaluate calcium charge and release of conventional glass-ionomer cement (GIC) containing nanoporous silica (NPS). Experimental specimens were divided into two groups: the control (GIC containing no NPS) and GIC-NPS (GIC containing 10 wt % NPS). The specimens were immersed in calcium chloride solutions of 5 wt % calcium concentration for 24 h at 37 °C, whereupon the calcium ion release of the specimens was measured. The calcium ion release behavior of GIC-NPS after immersion in the calcium solution was significantly greater than that of the control. Scanning electron microscopy and electron-dispersive X-ray spectroscopy results indicated that calcium penetrated inside the GIC-NPS specimen, while the calcium was primarily localized on the surface of the control specimen. It was demonstrated that NPS markedly improved the calcium charge and release property of GIC.