Theranostic Fibers for Simultaneous Imaging and Drug Delivery

New methods for creating theranostic systems with simultaneous encapsulation of therapeutic, diagnostic, and targeting agents are much sought after. This work reports for the first time the use of coaxial electrospinning to prepare such systems in the form of core–shell fibers. Eudragit S100 was used to form the shell of the fibers, while the core comprised poly(ethylene oxide) loaded with the magnetic resonance contrast agent Gd(DTPA) (Gd(III) diethylenetriaminepentaacetate hydrate) and indomethacin as a model therapeutic agent. The fibers had linear cylindrical morphologies with clear core–shell structures, as demonstrated by electron microscopy. X-ray diffraction and differential scanning calorimetry proved that both indomethacin and Gd(DTPA) were present in the fibers in the amorphous physical form. This is thought to be a result of intermolecular interactions between the different components, the presence of which was suggested by infrared spectroscopy. In vitro dissolution tests indicated that the fibers could provide targeted release of the active ingredients through a combined mechanism of erosion and diffusion. The proton relaxivities for Gd(DTPA) released from the fibers into tris buffer increased (r1 = 4.79–9.75 s–1 mM–1; r2 = 7.98–14.22 s–1 mM–1) compared with fresh Gd(DTPA) (r1 = 4.13 s–1 mM–1 and r2 = 4.40 s–1 mM–1), which proved that electrospinning has not diminished the contrast properties of the complex. The new systems reported herein thus offer a new platform for delivering therapeutic and imaging agents simultaneously to the colon

Electrospun medicated shellac nanofibers for colon-targeted drug delivery

Medicated shellac nanofibers providing colon-specific sustained release were fabricated using coaxial electrospinning. A solution of 7.5 g shellac and 1.5 g of ferulic acid (FA) in 10 mL ethanol was used as the core fluid, and a mixture of ethanol and N,N-dimethylformamide (8/10 v/v) as the shell. The presence of the shell fluid was required to prevent frequent clogging of the spinneret. The diameters of the fibers (D) can be manipulated by varying the ratio of shell to core flow rates (F), according to the equation D = 0.52F−0.19. Scanning electron microscopy images revealed that fibers prepared with F values of 0.1 and 0.25 had linear morphologies with smooth surfaces, but when the shell fluid flow rate was increased to 0.5 the fiber integrity was compromised. FA was found to be amorphously distributed in the fibers on the basis of X-ray diffraction and differential scanning calorimetry results. This can be attributed to good compatibility between the drug and carrier: IR spectra indicated the presence of hydrogen bonds between the two. In vitro dissolution tests demonstrated that there was minimal FA release at pH 2.0, and sustained release in a neutral dissolution medium. The latter occurred through an erosion mechanism. During the dissolution processes, the shellac fibers were gradually converted into nanoparticles as the FA was freed into solution, and ultimately completely dissolved

Nanofibers fabricated using triaxial electrospinning as zero order drug delivery systems

A new strategy for creating functional trilayer nanofibers through triaxial electrospinning is demonstrated. Ethyl cellulose (EC) was used as the filament-forming matrix in the outer, middle, and inner working solutions and was combined with varied contents of the model active ingredient ketoprofen (KET) in the three fluids. Triaxial electrospinning was successfully carried out to generate medicated nanofibers. The resultant nanofibers had diameters of 0.74 ± 0.06 μm, linear morphologies, smooth surfaces, and clear trilayer nanostructures. The KET concentration in each layer gradually increased from the outer to the inner layer. In vitro dissolution tests demonstrated that the nanofibers could provide linear release of KET over 20 h. The protocol reported in this study thus provides a facile approach to creating functional nanofibers with sophisticated structural features

Medicated Janus fibers fabricated using a Teflon-coated side-by-side spinneret

A family of medicated Janus fibers that provides highly tunable biphasic drug release was fabricated using a side-by-side electrospinning process employing a Teflon-coated parallel spinneret. The coated spinneret facilitated the formation of a Janus Taylor cone and in turn high quality integrated Janus structures, which could not be reliably obtained without the Teflon coating. The fibers prepared had one side consisting of polyvinylpyrrolidone (PVP) K60 and ketoprofen, and the other of ethyl cellulose (EC) and ketoprofen. To modulate and tune drug release, PVP K10 was doped into the EC side in some cases. The fibers were linear and had flat morphologies with an indent in the center. They provide biphasic drug release, with the PVP K60 side dissolving very rapidly to deliver a loading dose of the active ingredient, and the EC side resulting in sustained release of the remaining ketoprofen. The addition of PVP K10 to the EC side was able to accelerate the second stage of release; variation in the dopant amount permitted the release rate and extent this phase to be precisely tuned. These results offer the potential to rationally design systems with highly controllable drug release profiles, which can complement natural biological rhythms and deliver maximum therapeutic effects

Magnetic field induced effects in the high source-drain bias current of weakly coupled vertical quantum dot molecules

We report on the basic properties of recently observed magnetic field resonance, induced time dependent oscillation, and hysteresis effects in the current flowing through two weakly coupled vertical quantum dots at high source-drain bias (up to a few tens of mV). These effects bare some similarity to those reported in the N=2 spin-blockade regime, usually for weak in-plane magnetic field, of quantum dot molecules and attributed to hyperfine coupling, except here the measurements are conducted outside of the spin-blockade regime and the out-of-plane magnetic field is up to ~6 T.Comment: 3 pages, 3 figures, accepted for publication in Physica E in EP2DS 17 conference proceeding

Two level anti-crossings high up in the single-particle energy spectrum of a quantum dot

We study the evolution with magnetic field of the single-particle energy levels high up in the energy spectrum of one dot as probed by the ground state of the adjacent dot in a weakly coupled vertical quantum dot molecule. We find that the observed spectrum is generally well accounted for by the calculated spectrum for a two-dimensional elliptical parabolic confining potential, except in several regions where two or more single-particle levels approach each other. We focus on two two-level crossing regions which show unexpected anti-crossing behavior and contrasting current dependences. Within a simple coherent level mixing picture, we can model the current carried through the coupled states of the probed dot provided the intrinsic variation with magnetic field of the current through the states (as if they were uncoupled) is accounted for by an appropriate interpolation scheme.Comment: 4 pages, 4 figures, accepted for publication in Physica E in MSS 13 conference proceeding

Anomalous Negative Magnetoresistance Caused by Non-Markovian Effects

A theory of recently discovered anomalous low-field magnetoresistance is developed for the system of two-dimensional electrons scattered by hard disks of radius $a,$ randomly distributed with concentration $n.$ For small magnetic fields the magentoresistance is found to be parabolic and inversely proportional to the gas parameter, $\delta \rho_{xx}/\rho \sim - (\omega_c \tau)^2 / n a^2.$ With increasing field the magnetoresistance becomes linear $\delta \rho_{xx}/\rho \sim - \omega_c \tau$ in a good agreement with the experiment and numerical simulations.Comment: 4 pages RevTeX, 5 figure

High-frequency hopping conductivity in the quantum Hall effect regime: Acoustical studies

The high-frequency conductivity of Si delta-doped GaAs/AlGaAs heterostructures is studied in the integer quantum Hall effect (QHE) regime, using acoustic methods. Both the real and the imaginary parts of the complex conductivity are determined from the experimentally observed magnetic field and temperature dependences of the velocity and the attenuation of a surface acoustic wave. It is demonstrated that in the structures studied the mechanism of low-temperature conductance near the QHE plateau centers is hopping. It is also shown that at magnetic fields corresponding to filling factors 2 and 4, the doped Si delta- layer efficiently shunts the conductance in the two-dimensional electron gas (2DEG) channel. A method to separate the two contributions to the real part of the conductivity is developed, and the localization length in the 2DEG channel is estimated.Comment: 8pages, 9 figure

Targeting lentiviral vectors to antigen-specific immunoglobulins

Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell Populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient rnethod to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and hi vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral Surface. This engineered vector could specifically bind to cells expressing Surface immunoglobulin recognizing CD20 (αCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing αCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin-specific cells to deliver a therapeutic effect. Such targeting lentivectors also Could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology

Testing quantum correlations in a confined atomic cloud by scattering fast atoms

We suggest measuring one-particle density matrix of a trapped ultracold atomic cloud by scattering fast atoms in a pure momentum state off the cloud. The lowest-order probability of the inelastic process, resulting in a pair of outcoming fast atoms for each incoming one, turns out to be given by a Fourier transform of the density matrix. Accordingly, important information about quantum correlations can be deduced directly from the differential scattering cross-section. A possible design of the atomic detector is also discussed.Comment: 5 RevTex pages, no figures, submitted to PR