A Preliminary Study of Thermosets from Epoxy Resins Made Using Low-Toxicity Furan-Based Diols.

Glycidyl ethers are prepared from a series of furan-based diols and cured with a diamine to form thermosets. The furan diols demonstrate lower toxicity than bisphenol-A in a prior study. The diglycidyl ethers show improved thermal stability compared to the parent diols. Cured thermosets are prepared at elevated temperature using isophorone diamine (IPDA). Glass transition temperatures are in the range of 30-54 °C and depend on the structure of the furan diol. Coatings are prepared on steel substrates and show very high hardness, good adhesion, and a range of flexibility. Properties compare favorably with a control based on a bisphenol-A epoxy resin. The study demonstrates that epoxy resins based on furan diols, which have been shown to have lower toxicity than bisphenol-A, can form thermosets having properties comparable to a standard epoxy resin system; and thus, are viable as replacements for bisphenol-A epoxy resins.

Bioenergetics of Axon Integrity and Its Regulation by Oligodendrocytes and Schwann Cells.

Axons are long slender portions of neurons that transmit electrical impulses to maintain proper physiological functioning. Axons in the central nervous system (CNS) and peripheral nervous system (PNS) do not exist in isolation but are found to form a complex association with their surrounding glial cells, oligodendrocytes and Schwann cells. These cells not only myelinate them for faster nerve impulse conduction but are also known to provide metabolic support. Due to their incredible length, continuous growth, and distance from the cell body (where major energy synthesis takes place), axons are in high energetic demand. The stability and integrity of axons have long been associated with axonal energy levels. The current mini-review is thus focused on how axons accomplish their high energetic requirement in a cell-autonomous manner and how the surrounding glial cells help them in maintaining their integrity by fulfilling their energy demands (non-cell autonomous trophic support). The concept that adjacent glial cells (oligodendrocytes and Schwann cells) provide trophic support to axons and assist them in maintaining their integrity comes from the conditional knockout research and the studies in which the metabolic pathways controlling metabolism in these glial cells are modulated and its effect on axonal integrity is evaluated. In the later part of the mini-review, the current knowledge of axon-glial metabolic coupling during various neurodegenerative conditions was discussed, along with the potential lacunae in our current understanding of axon-glial metabolic coupling.

Design and Characterization of Silver Nanoparticles of Different Species of Curcuma in the Treatment of Cancer Using Human Colon Cancer Cell Line (HT-29).

BACKGROUND: Cancer is a deadly disease responsible for worldwide mortality; usually, middle- and low-income countries have been more affected by cancer and are responsible for 70% of deaths. The present study was performed with the aim to design silver nanoparticles using three species of Curcuma, i.e., Curcuma longa, Curcuma aromatica, and Curcuma caesia. METHODS: The rhizomes of different plants were extracted with ethanol. The rhizome extracts were used to prepare silver nanoparticles. It was optimized at different pH, silver ion concentrations, and concentrations of plant extracts. The anticancer activity of prepared nanoparticles of C. longa, C. aromatica, and C. caesia was evaluated on a human colon cancer cell line (HT-29) using sulforhodamine B (SRB) assay. RESULTS: The percentage yield of C. longa, C. aromatica, and C. caesia was 11.34 g, 15.45 g, and 12.67 g, respectively. The results exhibited that the prepared nanoparticles were smooth and spherical. All the nanoparticles of rhizome extracts rescued the viability of HT-29 cells in a different extent. HT-29 cells were sensitive to prepared nanoparticles that induce more cytotoxicity towards cancer cells. CONCLUSION: Thus, the prepared silver nanoparticle of Curcuma species through green synthesis may help treat cancer with low toxicity.

Hot-Melt Extrusion-Based Fused Deposition Modeling 3D Printing of Atorvastatin Calcium Tablets: Impact of Shape and Infill Density on Printability and Performance.

The main objective of the current research was to investigate the effect of tablet shapes (heart-shaped and round tablets) and infill densities (50% and 100%) on the drug release profiles of 3D printed tablets prepared by hot-melt extrusion paired with fused deposition modeling techniques. Drug-loaded filaments of 1.5 mm and 2.5 mm diameters were extruded using a Process 11 mm hot-melt extruder employing atorvastatin calcium as a model drug and Kollicoat® IR, Kollidon® VA64, Kollidon® 12PF, and Kolliphor® P407 as hydrophilic polymers. Filaments of Kollicoat® IR in combination with Kollidon® VA64/Kollidon® 12PF has resulted in successful printing of immediate release tablets. The mechanical properties of drug-loaded filaments were evaluated using a 3-point bend test and stiffness test. The transformation of a crystalline drug to an amorphous form and the absence of drug-polymer interactions were confirmed by differential scanning calorimetry and Fourier transform infrared spectroscopy, respectively. The effect of infill density on drug release profiles was greater than that of tablet shape. The stability of 3D printed tablets was preserved even after storage under accelerated conditions (40 ± 2°C and 75 ± 5% RH) for 6 months. Thus, the 3D printing process of hot-melt extrusion paired with fused deposition modeling serves as an alternative manufacturing approach for developing patient-focused doses.

Direct Arylation of Distal and Proximal C(sp3)-H Bonds of t-Amines with Aryl Diazonium Tetrafluoroborates via Photoredox Catalysis.

A visible light-mediated arylation protocol for t-amines has been reported through the coupling of γ- and α-amino alkyl radicals with different aryl diazonium salts using Ru(bpy)3Cl2·6H2O as a photocatalyst. Structurally different 9-aryl-9,10-dihydroacridine, 1-aryl tetrahydroisoquinoline, hexahydropyrrolo[2,1-a]isoquinoline, and hexahydro-2H-pyrido[2,1-a]isoquinoline frameworks with different substitution patterns have been synthesized in good yield using this methodology.

p-Silylation of Arenes via Organic Photoredox Catalysis: Use of p-Silylated Arenes for Exclusive o-Silylation, o-Acylation, and o-Alkylation Reactions.

Photocatalytic regiospecific p-silylation of arenes has been achieved by the coupling of in situ generated silyl radical with arene radical cation. The strategy involves reductive activation of PhSe-SiR3 and single electron transfer from the electron rich arene to 9,10-dimethoxyanthracene radical cation (DMA•+). p-Silyl arenes, thus formed, are further utilized for exclusive o-silylation reaction and for regiospecific o-acylation as well as o-alkylation reaction.

p-Selective (sp2)-C-H functionalization for an acylation/alkylation reaction using organic photoredox catalysis.

p-Selective (sp2)-C-H functionalization of electron rich arenes has been achieved for acylation and alkylation reactions, respectively, with acyl/alkylselenides by organic photoredox catalysis involving an interesting mechanistic pathway.

Surface Functionalized Graphene Biosensor on Sapphire for Cancer Cell Detection.

Graphene has several unique physical, optical and electrical properties such as a two-dimensional (2D) planar structure, high optical transparency and high carrier mobility at room temperature. These make graphene interesting for electrical biosensing. Using a catalyst-free chemical vapor deposition (CVD) method, graphene film is grown on a sapphire substrate. There is a single or a few sheets as confirmed by Raman spectroscopy and atomic force microscopy (AFM). Electrical graphene biosensors are fabricated to detect large-sized biological analytes such as cancer cells. Human colorectal carcinoma cells are sensed by the resistance change of an active bio-functionalized graphene device as the cells are captured by the immobilized antibody surface. The functionalized sensors show an increase in resistance as large as ~20% of the baseline with a small number of adhered cells. This study suggests that the bio-functionalized electrical graphene sensors on sapphire, which is a highly transparent material, can potentially detect circulating tumor cells (CTCs) and monitor cellular electrical behavior while being compatible with fluorescence-based optical-detection bioassays.

Ultrafast response of monolayer molybdenum disulfide photodetectors.

The strong light emission and absorption exhibited by single atomic layer transitional metal dichalcogenides in the visible to near-infrared wavelength range make them attractive for optoelectronic applications. In this work, using two-pulse photovoltage correlation technique, we show that monolayer molybdenum disulfide photodetector can have intrinsic response times as short as 3 ps implying photodetection bandwidths as wide as 300 GHz. The fast photodetector response is a result of the short electron-hole and exciton lifetimes in this material. Recombination of photoexcited carriers in most two-dimensional metal dichalcogenides is dominated by nonradiative processes, most notable among which is Auger scattering. The fast response time, and the ease of fabrication of these devices, make them interesting for low-cost ultrafast optical communication links.

Application of ethylcellulose coating to hydrophilic matrices: a strategy to modulate drug release profile and reduce drug release variability.

Hydrophilic matrix tablets are commonly used for extended release dosage forms. For low aqueous-solubility drugs, there may be challenges in modulation of release profiles and achieving consistent release in physiological conditions. To evaluate potential formulation strategies, matrix tablets of a low-soluble drug, hydrochlorothiazide, were developed using hypromellose and two fillers of different solubility, lactose (soluble) or partially pregelatinized maize starch (partially soluble). Additionally, application of an insoluble barrier membrane, aqueous ethylcellulose coating system, and a hydrophilic pore former onto matrix tablets was evaluated. Drug release from uncoated matrix tablets was variable at different agitation rates. Evaluation of tablets in bio-relevant media using physiologically relevant residence time indicated variable and higher initial release rate for uncoated matrices containing lactose but more robust behavior for tablets containing partially pregelatinized starch. Such in vitro behavior may lead to erratic drug release in vivo, when comparing fed versus fasted conditions. Dissolution profiles from barrier membrane-coated tablets showed initial delay, followed by zero-order release kinetics, with reduction or elimination of variability compared to uncoated matrices. Such reduced variability may mitigate mechanical effects of post-prandial stomach. Effects of coating weight gain and inclusion levels of pore former were evaluated and found to be critical in achieving robust and stable release profiles.

Improvement of carrier mobility of top-gated SiC epitaxial graphene transistors using a PVA dielectric buffer layer.

The effects of treatment with polyvinyl alcohol (PVA) and a dielectric film of HfO(2) on the properties of SiC based epitaxial graphene have been explored and analyzed. We have characterized the carrier mobility of graphene on Si-face and C-face SiC with a layer of HfO(2), with or without an initial PVA treatment on the device active layer. Epitaxial graphene grown on the C-face displays a higher mobility than a film grown on the silicon face. Also, the mobility in the presence of the PVA treatment with HfO(2) dielectric layer has been improved, compared with the mobility after deposition of only gate dielectric: ∼20% in C-face graphene and ∼90% in Si-face graphene. This is a major improvement over the degradation normally observed with dielectric/graphene systems.

Charge trapping devices using a bilayer oxide structure.

This experiment is the first exploration of use of charge traps in the bulk of deposited top oxide and at the interface between thermal oxide and deposited top oxide. We report the operational characteristics of SiO2/SiO2 device structures with 0.5 microm gate width and length. Low power operations are achieved through very thin gate stacks of 3 nm of thermally grown oxide and 7 nm of deposited oxide. However, narrow memory windows have been acquired comparing with conventional silicon-oxide-nitride-oxide-silicon (SONOS) memory cells due to a low trap density at the interface between a grown oxide and a deposited oxide. Additionally, the electric field between the channel and the charge is determined by solving 1D Poisson equation at a given write voltage, then total tunneling current density is calculated to make a program modeling for charge trapping devices. Tunneling/trapping simulation based on Fowler-Nordheim (F-N) tunneling performed and it fits the programming curves well. The memory window is almost constant after 100,000 cycles, and the retention characteristics are deteriorated rapidly.

SiC surface orientation and Si loss rate effects on epitaxial graphene.

We have explored the properties of SiC-based epitaxial graphene grown in a cold wall UHV chamber. The effects of the SiC surface orientation and silicon loss rate were investigated by comparing the characteristics of each formed graphene. Graphene was grown by thermal decomposition on both the silicon (0001) and carbon (000-1) faces of on-axis semi-insulating 6H-SiC with a "face-down" and "face-up" orientations. The thermal gradient, in relation to the silicon flux from the surface, was towards the surface and away from the surface, respectively, in the two configurations. Raman results indicate the disorder characteristics represented by ID/IG down to < 0.02 in Si-face samples and < 0.05 in C-faces over the 1 cm2 wafer surface grown at 1,450°C. AFM examination shows a better morphology in face-down surfaces. This study suggests that the optimum configuration slows the thermal decomposition and allows the graphene to form near the equilibrium. The Si-face-down orientation (in opposition to the temperature gradient) results in a better combination of low disorder ratio, ID/IG, and smooth surface morphology. Mobility of Si-face-down orientation has been measured as high as approximately 1,500 cm2/Vs at room temperature. Additionally, the field effect transistors have been fabricated on both Si-face-down and C-face-down showing an ambipolar behavior with more favorable electron conduction.

Contactless measurement of surface dominated recombination in gold- and aluminum-catalyzed silicon vapor-liquid-solid wires.

Carrier lifetimes of Si micro/nanowires grown by the vapor-liquid-solid method are measured using an extension of the classic contactless photoconductivity decay method. The samples measured consist of a thin aggregated film of oxide passivated wires on a fused silica carrier. Au catalyzed wires in the 392-730 nm diameter range are studied. Recombination in these wires is controlled by the surface or near surface effects, not bulk Au impurities. The lifetimes of Au- and Al-catalyzed wires of comparable diameter are measured. The Al wires are found to have slightly longer lifetimes than those grown with Au at a comparable diameter. Across all samples, the lifetimes measured range was from 0.2 to 1.0 ns. The surface controlled nature of the recombination measured implies larger diameter wires will offer better performance in devices that rely on minority carrier transport.

Attofarad resolution capacitance-voltage measurement of nanometer scale field effect transistors utilizing ambient noise.

A high resolution capacitance-voltage (C-V) characterization technique, enabling direct measurement of electronic properties at the nanoscale in devices such as nanowire field effect transistors (FETs) through the use of random fluctuations, is described. The minimum noise level required for achieving sub-aF (10(-18) F) resolution, the leveraging of stochastic resonance, and the effect of higher levels of noise are illustrated through simulations. The non-linear DeltaC(gate-source/drain)-V(gate) response of FETs is utilized to determine the inversion layer capacitance (C(inv)) and carrier mobility. The technique is demonstrated by extracting the carrier concentration and effective electron mobility in a nanoscale Si FET with C(inv) = 60 aF.

Extended-release oral drug delivery technologies: monolithic matrix systems.

Oral drug delivery is the largest and the oldest segment of the total drug delivery market. It is the fastest growing and most preferred route for drug administration. Use of hydrophilic matrices for oral extended release of drugs is a common practice in the pharmaceutical industry. This chapter presents different polymer choices for fabrication of monolithic hydrophilic matrices and discusses formulation and manufacturing variables affecting the design and performance of the extended-release product by using selected practical examples.

Improved oral delivery of paclitaxel following administration in nanoemulsion formulations.

Nanoemulsion formulations were designed for enhancing the oral bioavailability of hydrophobic drugs. Paclitaxel was selected as a model hydrophobic drug, which is also a substrate for the P-glycoprotein efflux system. The oil-in-water (o/w) nanoemulsions were formulated with pine nut oil as the internal oil phase, egg lecithin as the primary emulsifier, and water as the external phase. Stearylamine and deoxycholic acid were used to impart positive and negative charge to the emulsions, respectively. Nanoemulsions were prepared by sonication method and characterized for particle size and surface charge. The control and nanoemulsion formulations with tritiated [3H]-paclitaxel were administered orally to female C57BL/6 mice and the distribution of the drug was examined. The formulated nanoemulsions had a particle size range of approximately 90-120 nm (laser diffraction method) and zeta potential values ranging from -56 mV to +34 mV. Following oral administration, a significantly higher concentration of paclitaxel was observed in the systemic circulation when administered in the nanoemulsion relative to control aqueous solution. The absorbed drug was found to be distributed in the liver, kidneys, and lungs. The results of this study suggest that nanoemulsions are promising novel formulations that can enhance the oral bioavailability of hydrophobic drugs, like paclitaxel.

A review of nanocarrier-based CNS delivery systems.

Drug delivery to the central nervous system (CNS) is one of the most challenging fields of research and development for pharmaceutical and biotechnology products. A number of hydrophilic therapeutic agents, such as antibiotics, anticancer agents, or newly developed neuropeptides do not cross the blood brain barrier (BBB) after systemic administration. The BBB is formed by the tight junctions at the brain capillary endothelial cells, which strictly control drug transfer from blood to brain. Drug modification, osmotic opening of cerebral capillary endothelium, and alternative routes for administration (e.g., intracerebral delivery) have been successfully used to enhance drug transport to the CNS. The use of nanocarriers, such as liposomes and solid polymeric or lipid nanoparticles may be advantageous over the current strategies. These nanocarriers can not only mask the BBB limiting characteristics of the therapeutic drug molecule, but may also protect the drug from chemical/enzymatic degradation, and additionally provide the opportunity for sustained release characteristics. Reduction of toxicity to peripheral organs can also be achieved with these nanocarriers. This review article discusses the various barriers for drug delivery to the CNS and reviews the current state of nanocarriers for enhancing drug transport into the CNS.

Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design.

The tremendous progress witnessed in the field of biotechnology with respect to discovery of therapeutic and antigenic proteins has propelled the need for development of suitable oral delivery devices for these and other macromolecules. In this study, we report the encapsulation of fluorescein isothiocyanate (FITC)-labeled gelatin nanoparticles into poly(epsilon-caprolactone) (PCL) microsphere (nanoparticle-in-microsphere oral delivery system, NiMOS) by double emulsion like technique and the influence of variables such as polymer concentration in organic phase, amount of nanoparticles added as internal phase, and the speed of homogenization on particle size of NiMOS using a 3(3) randomized full factorial design. A statistical model with interaction terms was derived to predict the particle size of the hybrid system. The results from multiple linear regression analysis and Student's t-test revealed that for obtaining large particles of NiMOS, a high polymer concentration and low speed of homogenization was necessary. In contrast, to obtain particles of smaller size, high speed of homogenization was found to be very important. The mathematical model obtained was validated for prediction of particle size. The encapsulation of gelatin nanoparticles in PCL microsphere was confirmed by fluorescent microscopy. Based on the statistical model we were also successful in producing NiMOS of less than 10 mum in size, which could be used as oral delivery system for therapeutic and antigenic macromolecules.

Formulation and physiological factors influencing CNS delivery upon intranasal administration.

The treatment of central nervous system (CNS) disorders is particularly challenging because of a variety of formidable barriers to effective and persistent delivery of therapeutic compounds. This review discusses the potential of intranasal drug administration as a means to bypass a major barrier, the blood-brain barrier, and allow for direct delivery of drugs into the CNS. The article emphasizes physicochemical properties of intranasal drug formulations as well as relevant anatomical and physiological factors in intranasal delivery of drugs for CNS therapy. Published examples of intranasal administration of small molecular weight drugs, peptides and proteins, and novel formulations for delivering a broad spectrum of molecules are discussed. Finally, the article provides several strategies for effectively enhancing nose-to-brain transport of drug molecules through rational formulation design and optimization.