Electrochemical Detection of Oxycodone and Its Main Metabolites with Nafion-Coated Single-Walled Carbon Nanotube Electrodes.

Oxycodone is a strong opioid frequently used as an analgesic. Although proven efficacious in the management of moderate to severe acute pain and cancer pain, use of oxycodone imposes a risk of adverse effects such as addiction, overdose, and death. Fast and accurate determination of oxycodone blood concentration would enable personalized dosing and monitoring of the analgesic as well as quick diagnostics of possible overdose in emergency care. However, in addition to the parent drug, several metabolites are always present in the blood after a dose of oxycodone, and to date, there is no electrochemical data available on any of these metabolites. In this paper, a single-walled carbon nanotube (SWCNT) electrode and a Nafion-coated SWCNT electrode were used, for the first time, to study the electrochemical behavior of oxycodone and its two main metabolites, noroxycodone and oxymorphone. Both electrode types could selectively detect oxycodone in the presence of noroxycodone and oxymorphone. However, we have previously shown that addition of a Nafion coating on top of the SWCNT electrode is essential for direct measurements in complex biological matrices. Thus, the Nafion/SWCNT electrode was further characterized and used for measuring clinically relevant concentrations of oxycodone in buffer solution. The limit of detection for oxycodone with the Nafion/SWCNT sensor was 85 nM, and the linear range was 0.5-10 µM in buffer solution. This study shows that the fabricated Nafion/SWCNT sensor has potential to be applied in clinical concentration measurements.

Photon-drag effect in single-walled carbon nanotube films.

We observed an interaction of single-walled carbon nanotube films with obliquely incident nanosecond laser radiation in visible and infrared regions generating unipolar voltage pulses replicating the shape of the laser pulses. The photoelectric signal significantly depends on the laser polarization and has maximum value at the laser beam incidence angle of ±65° and at the film thickness of 350 nm. The results are explained in the framework of the photon-drag effect.

Carbon nanotube films for ultrafast broadband technology.

Mode-locked sub-picosecond operation of Yb-, Er- and Tm:Hodoped fiber lasers operating at 1.05 microm, 1.56 microm and 1.99 microm, respectively, is demonstrated using the same sample carbon nanotube-based saturable absorber mirror. A mesh of single-walled carbon nanotubes was deposited on an Ag-mirror using a one-step dry-transfer contact press method to combine broadband saturable absorption and high reflectance properties. The novel fabrication method of the polymer-free absorber and device parameters determined using nonlinear reflectivity measurement are described in detail. To our knowledge the observed operation bandwidth of approximately 1 microm is the broadest reported to date for a single carbon nanotube-based saturable absorber.

Preparation of polymeric nanoparticles containing corticosteroid by a novel aerosol flow reactor method.

Polymeric drug-containing nanoparticles were prepared using a novel aerosol flow reactor method. The polymeric drug-containing nanoparticles prepared consist of a poorly water soluble corticosteroid, beclomethasone dipropionate, and polymeric materials Eudragit E 100 or Eudragit L 100. The novel method used in this study allows synthesis of nanoparticles directly as dry powders. The nanoparticles can contain various ratios of drug and polymer, and the use of any additional stabilisation materials is avoided. In this study, nanoparticles with different drug-to-polymer ratios were prepared. Particle size and morphology, crystallinity, and thermal behaviour were determined as a function of particle composition. It was found that all the nanoparticles produced, regardless of particle composition, had geometric number mean diameters of approximately 90 nm, and were spherical showing smooth surfaces. The drug was molecularly dispersed in the amorphous polymeric matrix of the nanoparticles, and drug crystallisation was not observed when the ambient temperature was below the glass transition temperature of the polymer.

Influence of the solvent composition on the aerosol synthesis of pharmaceutical polymer nanoparticles.

Spherical, Eudragit L100 polymer nanoparticles with and without a ketoprofen drug were prepared by a novel aerosol flow reactor method. In this method, the polymer solution is sprayed to form nanosized droplets followed by the evaporation of a solvent. A purpose of the work was to explore the effect of solvent, solvent mixture, and co-solute (ketoprofen) on the formation of polymer particle, and particularly on particle morphology. The solvents used, i.e. ethanol, THF, toluene, and water, were selected according to their vapor pressure and dissolution capability for the polymer. At the polymer concentration range from 0.2 to 1.5 g/l of the starting solution, the geometric number mean diameters (GMD) of the particles increased from 75 to 130 nm and from 65 to 100 nm from the solutions of ethanol and THF, respectively. Particle morphology was observed by a scanning electron microscope (SEM). Particles changed from collapsed to irregular via spherical shape in the course of the decreasing solubility of the polymer in the medium. This is critically dependent on the solvent evaporation rate as well as the solute solubility, i.e. fast evaporative removal of solvent results in collapsed particles whereas low solubility results in irregular particles. Interplay between the vapor pressure of the solvents and the polymer solubility in the medium made possible to prepare particles with more complicated structures such as shriveled and blistery structures. The particle morphology as detected by SEM did not change when 10 wt.% of ketoprofen was added to the precursor solution.

Nanoparticles containing ketoprofen and acrylic polymers prepared by an aerosol flow reactor method.

The purpose of this study was to outline the effects of interactions between a model drug and various acrylic polymers on the physical properties of nanoparticles prepared by an aerosol flow reactor method. The amount of model drug, ketoprofen, in the nanoparticles was varied, and the nanoparticles were analyzed for particle size distribution, particle morphology, thermal properties, IR spectroscopy, and drug release. The nanoparticles produced were spherical, amorphous, and had a matrix-type structure. Ketoprofen crystallization was observed when the amount of drug in Eudragit L nanoparticles was more than 33% (wt/wt). For Eudragit E and Eudragit RS nanoparticles, the drug acted as an effective plasticizer resulting in lowering of the glass transition of the polymer. Two factors affected the preparation of nanoparticles by the aerosol flow reactor method, namely, the solubility of the drug in the polymer matrix and the thermal properties of the resulting drug-polymer matrix.

Injected nanoparticles: the combination of experimental systems to assess cardiovascular adverse effects.

When nanocarriers are used for drug delivery they can often achieve superior therapeutic outcomes over standard drug formulations. However, concerns about their adverse effects are growing due to the association between exposure to certain nanosized particles and cardiovascular events. Here we examine the impact of intravenously injected drug-free nanocarriers on the cardiovasculature at both the systemic and organ levels. We combine in vivo and in vitro methods to enable monitoring of hemodynamic parameters in conscious rats, assessments of the function of the vessels after sub-chronic systemic exposure to nanocarriers and evaluation of the direct effect of nanocarriers on vascular tone. We demonstrate that nanocarriers can decrease blood pressure and increase heart rate in vivo via various mechanisms. Depending on the type, nanocarriers induce the dilation of the resistance arteries and/or change the responses induced by vasoconstrictor or vasodilator drugs. No direct correlation between physicochemical properties and cardiovascular effects of nanoparticles was observed. The proposed combination of methods empowers the studies of cardiovascular adverse effects of the nanocarriers.

Gas-phase synthesis of solid state DNA nanoparticles stabilized by l-leucine.

Aerosol flow reactor is used to generate solid-state nanoparticles in a one-step process that is based on drying of aerosol droplets in continuous flow. We investigated the applicability of aerosol flow reactor method to prepare solid state DNA nanoparticles. Precursor solutions of plasmid DNA with or without complexing agent (polyethylenimine), coating material (l-leucine) and mannitol (bulking material) were dispersed to nanosized droplets and instantly dried in laminar heat flow. Particle morphology, integrity and stability were studied by scanning electron microscopy. The stability of DNA was studied by gel electrophoresis. Plasmid DNA as such degraded in the aerosol flow process. Complexing agent protected DNA from degradation and coating material enabled production of dispersed, non-aggregated, nanoparticles. The resulting nanoparticles were spherical and their mean diameter ranged from 65 to 125nm. The nanoparticles were structurally stable at room temperature and their DNA content was about 10%. We present herein the proof of principle for the production of dispersed solid state nanoparticles with relevant size and intact plasmid DNA.

Modifying native nanocellulose aerogels with carbon nanotubes for mechanoresponsive conductivity and pressure sensing.

Mechanically excellent native cellulose nanofibers that are cleaved from plant cell walls have been modified by functionalized few-walled carbon nanotubes for hybrid nanofiber/nanotube aerogels. They show elastic mechanical behavior in combination with reversible electrical response under compression allowing responsive conductivity and pressure sensing. The concept combines wide availability of nanocellulosics and electrical functionality of carbon nanotubes synergistically.

Functional hydrophobin-coating of thermally hydrocarbonized porous silicon microparticles.

Porous silicon (PSi) particles have been widely used in modulating the dissolution rate of various types of drugs loaded within its mesopores. This material can be surface treated in order to vary its hydrophobicity and several other properties, such as drug loading degree and release rate. Hydrophobins are a family of self-assembling proteins of fungal origin which have the ability to form layers on hydrophobic materials. This type of protein layer can modify the characteristics and control the binding properties of the surface on which it assembles. In this study, we have developed a procedure to coat thermally hydrocarbonized-PSi microparticles with hydrophobin II (HFBII) in order to modify the particles' hydrophobicity and to improve their biocompatibility, while maintaining intact the advantageous drug releasing properties of the PSi. The HFBII content adsorbed onto the particles was successfully quantified by a protein assay. Drug dissolution and permeation across Caco-2 cell monolayers were also conducted, together with viability studies in AGS, Caco-2 and HT-29 cells. The characterization and coating stability assessment showed that the HFBII-coating desorbs partially from the particles' surface as the pH increases. The HFBII coating also improved the biocompatibility of the particles without compromising the enhanced drug permeation or release.

Ion-induced nucleation of dibutyl phthalate vapors on spherical and nonspherical singly and multiply charged polyethylene glycol ions.

Dibutyl phthalate vapor nucleation induced by positive polyethylene glycol (PEG) ions with controlled sizes and charges was experimentally studied. The ions were produced by electrospray ionization, classified in a high-resolution differential mobility analyzer, and studied in a nano condensation nucleus counter of the mixing type. Ionic radii of PEG varied from 0.52 to 1.56 nm, including from singly to quadruply charged ions. Some of these ions are fully stretched chains, other are spherical, and others have intermediate forms, all of them having been previously characterized by mobility and mass spectrometry studies. Activation of PEG1080(+2) requires a supersaturation almost as high as that required for small singly charged ions and higher than for PEG1080(+). This anomaly is explained by the Coulombic stretching of the ion into a long chain, where the two charged centers appear to be relatively decoupled from each other. The critical supersaturation for singly charged spherical ions falls below Thomson's (capillary) theory and even below the already low values seen previously for tetraheptyl ammonium bromide clusters. Spherical PEG4120(+2) falls close to the Thomson curve. The trends observed for slightly nonspherical PEG4120(+3) and highly nonspherical (but not quite linear) PEG4120(+4) are intermediate between those of multiply charged spheres and small singly charged ions.

Polymeric drug nanoparticles prepared by an aerosol flow reactor method.

PURPOSE: Our purpose was to study the possibility of using a novel method, namely, aerosol flow reactor method, for the preparation of drug-containing nanoparticles with varying amounts of drug and polymer. The physical properties of the prepared nanoparticles were analyzed. METHODS: The nanoparticle size distributions were measured using differential mobility analyzer. The structure of the prepared nanoparticles was assessed by x-ray diffraction, differential scanning calorimetry, and electron microscopy. Drug release from the nanoparticles was analyzed. RESULTS: The spherical particles produced showed a unimodal and lognormal size distribution, and the geometric number mean size of the nanoparticles could be varied between 90 and 200 nm. When the amount of drug in the polymeric matrix was small, the nanoparticles had a homogeneous, amorphous structure. Drug crystals were formed when the amount of drug was increased over the solubility limit of the drug into the polymer. The amounts of drug and polymer controlled the drug release from the nanoparticles. CONCLUSIONS: The aerosol flow reactor method was found to be able to produce homogeneous amorphous matrix-type nanoparticles that can directly be collected as dry powder.