Utilizing Laser Activation of Photothermal Plasmonic Nanoparticles to Induce On-Demand Drug Amorphization inside a Tablet.

Poor aqueous drug solubility represents a major challenge in oral drug delivery. A novel approach to overcome this challenge is drug amorphization inside a tablet, that is, on-demand drug amorphization. The amorphous form is a thermodynamically instable, disordered solid-state with increased dissolution rate and solubility compared to its crystalline counterpart. During on-demand drug amorphization, the drug molecularly disperses into a polymer to form an amorphous solid at elevated temperatures inside a tablet. This study investigates, for the first time, the utilization of photothermal plasmonic nanoparticles for on-demand drug amorphization as a new pharmaceutical application. For this, near-IR photothermal plasmonic nanoparticles were tableted together with a crystalline drug (celecoxib) and a polymer (polyvinylpyrrolidone). The tablets were subjected to a near-IR laser at different intensities and durations to study the rate of drug amorphization under each condition. During laser irradiation, the plasmonic nanoparticles homogeneously heated the tablet. The temperature was directly related to the rate and degree of amorphization. Exposure times as low as 180 s at 1.12 W cm-2 laser intensity with only 0.25 wt % plasmonic nanoparticles and up to 50 wt % drug load resulted in complete drug amorphization. Therefore, near-IR photothermal plasmonic nanoparticles are promising excipients for on-demand drug amorphization with laser irradiation.

The Effect of the Molecular Weight of Polyvinylpyrrolidone and the Model Drug on Laser-Induced In Situ Amorphization.

Laser radiation has been shown to be a promising approach for in situ amorphization, i.e., drug amorphization inside the final dosage form. Upon exposure to laser radiation, elevated temperatures in the compacts are obtained. At temperatures above the glass transition temperature (Tg) of the polymer, the drug dissolves into the mobile polymer. Hence, the dissolution kinetics are dependent on the viscosity of the polymer, indirectly determined by the molecular weight (Mw) of the polymer, the solubility of the drug in the polymer, the particle size of the drug and the molecular size of the drug. Using compacts containing 30 wt% of the drug celecoxib (CCX), 69.25 wt% of three different Mw of polyvinylpyrrolidone (PVP: PVP12, PVP17 or PVP25), 0.25 wt% plasmonic nanoaggregates (PNs) and 0.5 wt% lubricant, the effect of the polymer Mw on the dissolution kinetics upon exposure to laser radiation was investigated. Furthermore, the effect of the model drug on the dissolution kinetics was investigated using compacts containing 30 wt% of three different drugs (CCX, indomethacin (IND) and naproxen (NAP)), 69.25 wt% PVP12, 0.25 wt% PN and 0.5 wt% lubricant. In perfect correlation to the Noyes-Whitney equation, this study showed that the use of PVP with the lowest viscosity, i.e., the lowest Mw (here PVP12), led to the fastest rate of amorphization compared to PVP17 and PVP25. Furthermore, NAP showed the fastest rate of amorphization, followed by IND and CCX in PVP12 due to its high solubility and small molecular size.

Emulsions Stabilized by Chitosan-Modified Silica Nanoparticles: pH Control of Structure-Property Relations.

In food-grade emulsions, particles with an appropriate surface modification can be used to replace surfactants and potentially enhance the stability of emulsions. During the life cycle of products based on such emulsions, they can be exposed to a broad range of pH conditions and hence it is crucial to understand how pH changes affect stability of emulsions stabilized by particles. Here, we report on a comprehensive study of the stability, microstructure, and macroscopic behavior of pH-controlled oil-in-water emulsions containing silica nanoparticles modified with chitosan, a food-grade polycation. We found that the modified colloidal particles used as stabilizers behave differently depending on the pH, resulting in unique emulsion structures at multiple length scales. Our findings are rationalized in terms of the different emulsion stabilization mechanisms involved, which are determined by the pH-dependent charges and interactions between the colloidal building blocks of the system. At pH 4, the silica particles are partially hydrophobized through chitosan modification, favoring their adsorption at the oil-water interface and the formation of Pickering emulsions. At pH 5.5, the particles become attractive and the emulsion is stabilized by a network of agglomerated particles formed between the droplets. Finally, chitosan aggregates form at pH 9 and these act as the emulsion stabilizers under alkaline conditions. These insights have important implications for the processing and use of particle-stabilized emulsions. On one hand, changes in pH can lead to undesired macroscopic phase separation or coalescence of oil droplets. On the other hand, the pH effect on emulsion behavior can be harnessed in industrial processing, either to tune their flow response by altering the pH between processing stages or to produce pH-responsive emulsions that enhance the functionality of the emulsified end products.

Investigation of the Intra- and Interlaboratory Reproducibility of a Small Scale Standardized Supersaturation and Precipitation Method.

The high number of poorly water-soluble compounds in drug development has increased the need for enabling formulations to improve oral bioavailability. One frequently applied approach is to induce supersaturation at the absorptive site, e.g., the small intestine, increasing the amount of dissolved compound available for absorption. However, due to the stochastic nature of nucleation, supersaturating drug delivery systems may lead to inter- and intrapersonal variability. The ability to define a feasible range with respect to the supersaturation level is a crucial factor for a successful formulation. Therefore, an in vitro method is needed, from where the ability of a compound to supersaturate can be defined in a reproducible way. Hence, this study investigates the reproducibility of an in vitro small scale standardized supersaturation and precipitation method (SSPM). First an intralaboratory reproducibility study of felodipine was conducted, after which seven partners contributed with data for three model compounds; aprepitant, felodipine, and fenofibrate, to determine the interlaboratory reproducibility of the SSPM. The first part of the SSPM determines the apparent degrees of supersaturation (aDS) to investigate for each compound. Each partner independently determined the maximum possible aDS and induced 100, 87.5, 75, and 50% of their determined maximum possible aDS in the SSPM. The concentration-time profile of the supersaturation and following precipitation was obtained in order to determine the induction time (tind) for detectable precipitation. The data showed that the absolute values of tind and aDS were not directly comparable between partners, however, upon linearization of the data a reproducible rank ordering of the three model compounds was obtained based on the ß-value, which was defined as the slope of the ln(tind) versus ln(aDS)-2 plot. Linear regression of this plot showed that aprepitant had the highest ß-value, 15.1, while felodipine and fenofibrate had comparable ß-values, 4.0 and 4.3, respectively. Of the five partners contributing with full data sets, 80% could obtain the same rank order for the three model compounds using the SSPM (aprepitant > felodipine ≈ fenofibrate). The α-value is dependent on the experimental setup and can be used as a parameter to evaluate the uniformity of the data set. This study indicated that the SSPM was able to obtain the same rank order of the ß-value between partners and, thus, that the SSPM may be used to classify compounds depending on their supersaturation propensity.

Multifractal Characterization of Pharmaceutical Hot-Melt Extrudates.

PURPOSE: Multifractal geometry has become a powerful tool to describe complex structures in many fields. Our first aim was to combine imaging and multifractal analysis to better understand the microstructure of pharmaceutical extrudates. A second objective was to study erosion/dispersion behavior of the formulations because it would condition release of any drug. METHODS: Different formulations containing a lipid, a polymer and different silica based inorganic carriers were produced by hot-melt extrusion at various screw speeds. Multifractal analysis was based on scanning electron microscopy/energy dispersive X-Ray spectroscopy images. This microstructural analysis was complemented with dynamic optical imaging of formulation erosion/dispersion behavior. RESULTS: Multifractal analysis indicated that inorganic carrier type and concentration as well as the screw speed affected the microstructure of the extrudates. The aqueous erosion/dispersion study showed that only the type and concentration of inorganic carrier were important. CONCLUSIONS: The use of microstructural and dispersion analysis appeared to be complementary to better characterize and understand complex formulations obtained by hot-melt extrusion.

Pickering and Network Stabilization of Biocompatible Emulsions Using Chitosan-Modified Silica Nanoparticles.

Edible solid particles constitute an attractive alternative to surfactants as stabilizers of food-grade emulsions for products requiring a long-term shelf life. Here, we report on a new approach to stabilize edible emulsions using silica nanoparticles modified by noncovalently bound chitosan oligomers. Electrostatic modification with chitosan increases the hydrophobicity of the silica nanoparticles and favors their adsorption at the oil-water interface. The interfacial adsorption of the chitosan-modified silica particles enables the preparation of oil-in-water emulsions with small droplet sizes of a few micrometers through high-pressure homogenization. This approach enables the stabilization of food-grade emulsions for more than 3 months. The emulsion structure and stability can be effectively tuned by controlling the extent of chitosan adsorption on the silica particles. Bulk and interfacial rheology are used to highlight the two stabilization mechanisms involved. Low chitosan concentration (1 wt % with respect to silica) leads to the formation of a viscoelastic film of particles adsorbed at the oil-water interface, enabling Pickering stabilization of the emulsion. By contrast, a network of agglomerated particles formed around the droplets is the predominant stabilization mechanism of the emulsions at higher chitosan content (5 wt % with respect to silica). These two pathways against droplet coalescence and coarsening open up different possibilities to engineer the long-term stabilization of emulsions for food applications.

Iron oxide nanoparticles for treatment and diagnosis of chronic inflammatory diseases: A systematic review.

Chronic inflammatory conditions are among the most prevalent diseases worldwide. Several debilitating diseases such as atherosclerosis, inflammatory bowel disease, rheumatoid arthritis, and Alzheimer's are linked to chronic inflammation. These conditions often develop into complex and fatal conditions, making early detection and treatment of chronic inflammation crucial. Current diagnostic methods show high variability and do not account for disease heterogeneity and disease-specific proinflammatory markers, often delaying the disease detection until later stages. Furthermore, existing treatment strategies, including high-dose anti-inflammatory and immunosuppressive drugs, have significant side effects and an increased risk of infections. In recent years, superparamagnetic iron oxide nanoparticles (SPIONs) have shown tremendous biomedical potential. SPIONs can function as imaging modalities for magnetic resonance imaging, and as therapeutic agents due to their magnetic hyperthermia capability. Furthermore, the surface functionalization of SPIONs allows the detection of specific disease biomarkers and targeted drug delivery. This systematic review explores the utility of SPIONs against chronic inflammatory disorders, focusing on their dual role as diagnostic and therapeutic agents. We extracted studies indexed in the Web of Science database from the last 10 years (2013-2023), and applied systematic inclusion criteria. This resulted in a final selection of 38 articles, which were analyzed for nanoparticle characteristics, targeted diseases, in vivo and in vitro models used, and the efficacy of the therapeutic or diagnostic modalities. The results revealed that ultrasmall SPIONs are excellent for imaging arterial and neuronal inflammation. Furthermore, novel therapies using SPIONs loaded with chemotherapeutic drugs show promise in the treatment of inflammatory diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Pharmaceutical Quality by Design Approach to Develop High-Performance Nanoparticles for Magnetic Hyperthermia.

Magnetic hyperthermia holds significant therapeutic potential, yet its clinical adoption faces challenges. One obstacle is the large-scale synthesis of high-quality superparamagnetic iron oxide nanoparticles (SPIONs) required for inducing hyperthermia. Robust and scalable manufacturing would ensure control over the key quality attributes of SPIONs, and facilitate clinical translation and regulatory approval. Therefore, we implemented a risk-based pharmaceutical quality by design (QbD) approach for SPION production using flame spray pyrolysis (FSP), a scalable technique with excellent batch-to-batch consistency. A design of experiments method enabled precise size control during manufacturing. Subsequent modeling linked the SPION size (6-30 nm) and composition to intrinsic loss power (ILP), a measure of hyperthermia performance. FSP successfully fine-tuned the SPION composition with dopants (Zn, Mn, Mg), at various concentrations. Hyperthermia performance showed a strong nonlinear relationship with SPION size and composition. Moreover, the ILP demonstrated a stronger correlation to coercivity and remanence than to the saturation magnetization of SPIONs. The optimal operating space identified the midsized (15-18 nm) Mn0.25Fe2.75O4 as the most promising nanoparticle for hyperthermia. The production of these nanoparticles on a pilot scale showed the feasibility of large-scale manufacturing, and cytotoxicity investigations in multiple cell lines confirmed their biocompatibility. In vitro hyperthermia studies with Caco-2 cells revealed that Mn0.25Fe2.75O4 nanoparticles induced 80% greater cell death than undoped SPIONs. The systematic QbD approach developed here incorporates process robustness, scalability, and predictability, thus, supporting the clinical translation of high-performance SPIONs for magnetic hyperthermia.

Magnetoresponsive fluorescent core-shell nanoclusters for biomedical applications.

Nowadays, superparamagnetic iron oxide nanoparticles (SPIONs) have a dominant role in many subfields of biomedicine. Owing to their peculiar properties, they can be employed for magnetic separation, drug delivery, diagnostics, and hyperthermia treatments. However, these magnetic nanoparticles (NPs) suffer from low unit magnetization due to size constraints (up to 20-30 nm) to exhibit superparamagnetic character. In this work, we have designed and synthesized superparamagnetic nanoclusters (SP-NCs) with diameters of up to 400 nm with high unit magnetization for enhanced loading capacity. These were synthesized with conventional or microwave-assisted solvothermal methods, in the presence of either of the two biomolecules (citrate or l-lysine) as the capping agent. Primary particle size, SP-NC size, surface chemistry, and the resultant magnetic properties were observed to be significantly influenced by the choice of synthesis route and capping agent. Selected SP-NCs were then coated with a fluorophore-doped silica shell to provide fluorescence properties, in the near-infrared spectrum region, while silica provided high chemical and colloidal stability. Heating efficiency studies were performed under alternating magnetic field on the synthesized SP-NCs, highlighting their potential in hyperthermia treatment. We envision that their enhanced magnetically-active content, fluorescence, magnetic property, and heating efficiency will pave the way to more effective uses in biomedical applications.

Synergistic stabilization of emulsion gel by nanoparticles and surfactant enables 3D printing of lipid-rich solid oral dosage forms.

Pharmaceutical formulation of oral dosage forms is continuously challenged by the low solubility of new drug candidates. Pickering emulsions, emulsions stabilized with solid particles, are a promising alternative to surfactants for developing long-term stable emulsions that can be tailored for controlled release of lipophilic drugs. In this work, a non-emulsifying lipid-based formulation (LBF) loaded with fenofibrate was formulated into an oil-in-water (O/W) emulsion synergistically stabilized by stearic acid and silica (SiO2) nanoparticles. The emulsion had a droplet size of 341 nm with SiO2 particles partially covering the oil-water interface. In vitro lipid digestion was faster for the emulsion compared to the corresponding LBF due to the larger total surface area available for digestion. Cellulose biopolymers were added to the emulsion to produce a gel for semi-solid extrusion (SSE) 3D printing into tablets. The emulsion gel showed suitable rheological attributes for SSE, with a trend of higher viscosity, yield stress, and storage modulus (G'), compared to a conventional self-emulsifying lipid-based emulsion gel. The developed emulsion gel allows for a non-emulsifying LBF to be transformed into solid dosage forms for rapid lipid digestion and drug release of a poorly water-soluble drug in the small intestine.

Intrinsic lipolysis rate for systematic design of lipid-based formulations.

Lipid-based formulations (LBFs) are used by the pharmaceutical industry in oral delivery systems for both poorly water-soluble drugs and biologics. Digestibility is key for the performance of LBFs and in vitro lipolysis is commonly used to compare the digestibility of LBFs. Results from in vitro lipolysis experiments depend highly on the experimental conditions and formulation characteristics, such as droplet size (which defines the surface area available for digestion) and interfacial structure. This study introduced the intrinsic lipolysis rate (ILR) as a surface area-independent approach to compare lipid digestibility. Pure acylglycerol nanoemulsions, stabilized with polysorbate 80 at low concentration, were formulated and digested according to a standardized pH-stat lipolysis protocol. A methodology originally developed to calculate the intrinsic dissolution rate of poorly water-soluble drugs was adapted for the rapid calculation of ILR from lipolysis data. The impact of surfactant concentration on the apparent lipolysis rate and lipid structure on ILR was systematically investigated. The surfactant polysorbate 80 inhibited lipolysis of tricaprylin nanoemulsions in a concentration-dependent manner. Coarse-grained molecular dynamics simulations supported these experimental observations. In the absence of bile and phospholipids, tricaprylin was shielded from lipase at 0.25% polysorbate 80. In contrast, the inclusion of bile salt and phospholipid increased the surfactant-free area and improved the colloidal presentation of the lipids to the enzyme, especially at 0.125% polysorbate 80. At a constant and low surfactant content, acylglycerol digestibility increased with decreasing acyl chain length, decreased esterification, and increasing unsaturation. The calculated ILR of pure acylglycerols was successfully used to accurately predict the IRL of binary lipid mixtures. The ILR measurements hold great promise as an efficient method supporting pharmaceutical formulation scientists in the design of LBFs with specific digestion profiles.

Hyperthermia-Induced In Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms.

Superparamagnetic iron oxide nanoparticles (SPIONs) generate heat upon exposure to an alternating magnetic field (AMF), which has been studied for hyperthermia treatment and triggered drug release. This study introduces a novel application of magnetic hyperthermia to induce amorphization of a poorly aqueous soluble drug, celecoxib, in situ in tablets for oral administration. Poor aqueous solubility of many drug candidates is a major hurdle in oral drug development. A novel approach to overcome this challenge is in situ amorphization of crystalline drugs. This method facilitates amorphization by molecular dispersion of the drug in a polymeric network inside a tablet, circumventing the physical instability encountered during the manufacturing and storage of conventional amorphous solid dispersions. However, the current shortcomings of this approach include low drug loading, toxicity of excipients, and drug degradation. Here, doped SPIONs produced by flame spray pyrolysis are compacted with polyvinylpyrrolidone and celecoxib and exposed to an AMF in solid state. A design of experiments approach was used to investigate the effects of SPION composition (Zn0.5Fe2.5O4 and Mn0.5Fe2.5O4), doped SPION content (10-20 wt %), drug load (30-50 wt %), and duration of AMF (3-15 min) on the degree of drug amorphization. The degree of amorphization is strongly linked to the maximum tablet temperature achieved during the AMF exposure (r = 0.96), which depends on the SPION composition and content in the tablets. Complete amorphization is achieved with 20 wt % Mn0.5Fe2.5O4 and 30 wt % celecoxib in the tablets that reached the maximum temperature of 165.2 °C after 15 min of AMF exposure. Furthermore, manganese ferrite exhibits no toxicity in human intestinal Caco-2 cell lines. The resulting maximum solubility of in situ amorphized celecoxib is 5 times higher than that of crystalline celecoxib in biorelevant intestinal fluid. This demonstrates the promising capability of SPIONs as enabling excipients to magnetically induce amorphization in situ in oral dosage forms.

Nanosilver on nanostructured silica: Antibacterial activity and Ag surface area.

Nanosilver is one of the first nanomaterials to be closely monitored by regulatory agencies worldwide motivating research to better understand the relationship between Ag characteristics and antibacterial activity. Nanosilver immobilized on nanostructured silica facilitates such investigations as the SiO2 support hinders the growth of nanosilver during its synthesis and, most importantly, its flocculation in bacterial suspensions. Here, such composite Ag/silica nanoparticles were made by flame spray pyrolysis of appropriate solutions of Ag-acetate or Ag-nitrate and hexamethyldisiloxane or tetraethylorthosilicate in ethanol, propanol, diethylene glucolmonobutyl ether, acetonitrile or ethylhexanoic acid. The effect of solution composition on nanosilver characteristics and antibacterial activity against the Gram negative Escherichia coli was investigated by monitoring their recombinantly synthesized green fluorescent protein. Suspensions with identical Ag mass concentration exhibited drastically different antibacterial activity pointing out that the nanosilver surface area concentration rather than its mass or molar or number concentration determine best its antibacterial activity. Nanosilver made from Ag-acetate showed a unimodal size distribution, while that made from inexpensive Ag-nitrate exhibited a bimodal one. Regardless of precursor composition or nanosilver size distribution, the antibacterial activity of nanosilver was correlated best with its surface area concentration in solution.

3D-printing of solid lipid tablets from emulsion gels.

Interest in 3D-printing technologies for pharmaceutical manufacturing of oral dosage forms is driven by the need for personalized medicines. Most research to date has focused on printing of polymeric-based drug delivery systems at high temperatures. Furthermore, oral formulation development is continuously challenged by the large number of poorly water-soluble drugs, which require more advanced enabling formulations to improve oral bioavailability. In this work, we used semi-solid extrusion (SSE) printing of emulsion gels with three types of emulsified lipid-based formulations (LBFs) to produce solid lipid tablets incorporating the poorly water-soluble drug, fenofibrate. Tablets were successfully 3D-printed from emulsion gels using SSE at room temperature, making the methodology particularly useful for thermolabile compounds. The tablets were well-defined in mass and disintegrated rapidly (<15 min). Importantly, the oil droplet size reconstituted after dispersion of the tablets and subsequent lipid digestion was similar to traditional liquid LBFs. This work demonstrates the successful use of SSE for fabricating solid lipid tablets based on emulsion gels. The method is further promising for on demand production of personalized dosage forms, necessary for flexible dosage adjustment in e.g., pediatric patients, when poorly water-soluble compounds constitute the core of the therapy.

The Influence of Drug-Polymer Solubility on Laser-Induced In Situ Drug Amorphization Using Photothermal Plasmonic Nanoparticles.

In this study, laser-induced in situ amorphization (i.e., amorphization inside the final dosage form) of the model drug celecoxib (CCX) with six different polymers was investigated. The drug-polymer combinations were studied with regard to the influence of (i) the physicochemical properties of the polymer, e.g., the glass transition temperature (Tg) and (ii) the drug-polymer solubility on the rate and degree of in situ drug amorphization. Compacts were prepared containing 30 wt% CCX, 69.25 wt% polymer, 0.5 wt% lubricant, and 0.25 wt% plasmonic nanoparticles (PNs) and exposed to near-infrared laser radiation. Upon exposure to laser radiation, the PNs generated heat, which allowed drug dissolution into the polymer at temperatures above its Tg, yielding an amorphous solid dispersion. It was found that in situ drug amorphization was possible for drug-polymer combinations, where the temperature reached during exposure to laser radiation was above the onset temperature for a dissolution process of the drug into the polymer, i.e., TDStart. The findings of this study showed that the concept of laser-induced in situ drug amorphization is applicable to a range of polymers if the drug is soluble in the polymer and temperatures during the process are above TDStart.

Proteomics-Informed Identification of Luminal Targets For In Situ Diagnosis of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic condition resulting in impaired intestinal homeostasis. Current practices for diagnosis of IBD are challenged by invasive, demanding procedures. We hypothesized that proteomics analysis could provide a powerful tool for identifying clinical biomarkers for non-invasive IBD diagnosis. Here, the global intestinal proteomes from commonly used in vitro and in vivo models of IBD were analyzed to identify apical and luminal proteins that can be targeted by orally delivered diagnostic agents. Global proteomics analysis revealed upregulated plasma membrane proteins in intestinal segments of proximal- and distal colon from dextran sulfate sodium-treated mice and also in inflamed human intestinal Caco-2 cells pretreated with pro-inflammatory agents. The upregulated colon proteins in mice were compared to the proteome of the healthy ileum, to ensure targeting of diagnostic agents to the inflamed colon. Promising target proteins for future investigations of non-invasive diagnosis of IBD were found in both systems and included Tgm2/TGM2, Icam1/ICAM1, Ceacam1/CEACAM1, and Anxa1/ANXA1. Ultimately, these findings will guide the selection of appropriate antibodies for surface functionalization of imaging agents aimed to target inflammatory biomarkers in situ.

Non-toxic dry-coated nanosilver for plasmonic biosensors.

The plasmonic properties of noble metals facilitate their use for in-vivo bio-applications such as targeted drug delivery and cancer cell therapy. Nanosilver is best suited for such applications as it has the lowest plasmonic losses among all such materials in the UV-visible spectrum. Its toxicity, however, can destroy surrounding healthy tissues and thus, hinders its safe use. Here, that toxicity against a model biological system (Escherichia coli) is "cured" or blocked by coating nanosilver hermetically with a about 2 nm thin SiO2 layer in one-step by a scalable flame aerosol method followed by swirl injection of a silica precursor vapor (hexamethyldisiloxane) without reducing the plasmonic performance of the enclosed or encapsulated silver nanoparticles (20 - 40 nm in diameter as determined by X-ray diffraction and microscopy). This creates the opportunity to safely use powerful nanosilver for intracellular bio-applications. The label-free biosensing and surface bio-functionalization of these ready-to-use, non-toxic (benign) Ag nanoparticles is presented by measuring the adsorption of bovine serum albumin (BSA) in a model sensing experiment. Furthermore, the silica coating around nanosilver prevents its agglomeration or flocculation (as determined by thermal annealing, optical absorption spectroscopy and microscopy) and thus, enhances its biosensitivity, including bioimaging as determined by dark field illumination.

Continuous surface functionalization of flame-made TiO2 nanoparticles.

Hydrophilic TiO(2) particles made in a flame aerosol reactor were converted in situ to hydrophobic ones by silylation of their surface hydroxyl groups. So the freshly formed titania aerosol was mixed with a fine spray of octyltriethoxysilane (OTES) in water/ethanol solution and functionalized continuously at high temperature. The extent of functionalization and structure of that surface layer were assessed by thermogravimetric analysis (TGA) coupled to mass spectroscopy (MS), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and Raman spectroscopy. Product particles were characterized also by transmission electron microscopy (TEM), X-ray diffraction, and nitrogen adsorption. The influence of titania specific surface area (SSA) and OTES solution concentration on the functional group surface density was investigated. The titanium dioxide surface was covered with functional groups (up to 2.9 wt %) that were thermally stable up to 300 degrees C in air at an average density of 2 OTES/nm(2). Such surface-functionalized particle suspensions in 2-ethylhexanoic acid and xylene were stable over several weeks. In contrast, as-prepared hydrophilic TiO(2) precipitated within days in these solvents.

Semiconductor gas sensors: dry synthesis and application.

Since the development of the first chemoresistive metal oxide based gas sensors, transducers with innovative properties have been prepared by a variety of wet- and dry-deposition methods. Among these, direct assembly of nanostructured films from the gas phase promises simple fabrication and control and with the appropriate synthesis and deposition methods nm to µm thick films, can be prepared. Dense structures are achieved by tuning chemical or vapor deposition methods whereas particulate films are obtained by deposition of airborne, mono- or polydisperse, aggregated or agglomerated nanoparticles. Innovative materials in non-equilibrium or sub-stoichiometric states are captured by rapid cooling during their synthesis. This Review presents some of the most common chemical and vapor-deposition methods for the synthesis of semiconductor metal oxide based detectors for chemical gas sensors. In addition, the synthesis of highly porous films by novel aerosol methods is discussed. A direct comparison of structural and chemical properties with sensing performance is given.