Electrosprayed Janus Particles for Combined Photo-Chemotherapy

This work is a proof of concept study establishing the potential of electrosprayed Janus particles for combined photodynamic therapy-chemotherapy. Sub-micron-sized particles of polyvinylpyrrolidone containing either an anti-cancer drug (carmofur) or a photosensitiser (rose bengal; RB), and Janus particles containing both in separate compartments were prepared. The functional components were present in the amorphous form in all the particles, and infrared spectroscopy indicated that intermolecular interactions formed between the different species. In vitro drug release studies showed that both carmofur and RB were released at approximately the same rate, with dissolution complete after around 250 min. Cytotoxicity studies were undertaken on model human dermal fibroblasts (HDF) and lung cancer (A549) cells, and the influence of light on cell death explored. Formulations containing carmofur as the sole active ingredient were highly toxic to both cell lines, with or without a light treatment. The RB formulations were non-toxic to HDF when no light was applied, and with photo-treatment caused large amounts of cell death for both A549 and HDF cells. The Janus formulation containing both RB and carmofur was non-toxic to HDF without light, and only slightly toxic with the photo-treatment. In contrast, it was hugely toxic to A549 cells when light was applied. The Janus particles are thus highly selective for cancer cells, and it is hence proposed that such electrosprayed particles containing both a chemotherapeutic agent and photosensitiser have great potential in combined chemotherapy/photodynamic therapy

No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

BACKGROUND: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS. OBJECTIVES: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease. METHODS: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres. RESULTS: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls. CONCLUSION: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority

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

Electrospun pH-sensitive core-shell polymer nanocomposites fabricated using a tri-axial process

A modified tri-axial electrospinning process was developed for the generation of a new type of pH-sensitive polymer/lipid nanocomposite. The systems produced are able to promote both dissolution and permeation of a model poorly water-soluble drug. First, we show that it is possible to run a tri-axial procress with only one of the three fluids being electrospinnable. Using an electrospinnable middle fluid of Eudragit S100 (ES100) with pure ethanol as the outer solvent and an unspinnable lecithin-diclofenac sodium (PL-DS) core solution, nanofibers with linear morphology and clear core/shell structures can be fabricated continuously and smoothly. X-ray diffraction proved that these nanofibers are structural nanocomposites with the drug present in an amorphous state. In vitro dissolution tests demonstrated that the formulations could preclude release in acidic conditions, and that the drug was released from the fibers in two successive steps at neutral pH. The first step is the dissolution of the shell ES100 and the conversion of the core PL-DS into sub-micron sized particles. This frees some DS into solution, and later the remaining DS is gradually released from the PL-DS particles through diffusion. Ex vivo permeation results showed that the composite nanofibers give a more than two-fold uplift in the amount of DS passing through the colonic membrane as compared to pure DS; 74% of the transmitted drug was in the form of PL-DS particles. The new tri-axial electrospinning process developed in this work provides a platform to fabricate structural nanomaterials, and the core-shell polymer-PL nanocomposites we have produced have significant potential applications for oral colon-targeted drug delivery. STATEMENT OF SIGNIFICANCE: A modified tri-axial electrospinning is demonstrated to create a new type of core-shell pH-sensitive polymer/lipid nanocomposites, in which an electrospinnable middle fluid is exploited to support the un-spinnable outer and inner fluids. The structural nanocomposites are able to provide a colon-targeted sustained release and an enhanced permeation performance of diclofenac sodium. The developed tri-axial process can provide a platform for fabricating new structural nanomaterials with high quality. The strategy of a combined usage of polymeric excipients and phosphilipid in a core-shell format should provide new possibilities of developing novel drug delivery systems for efficacious oral administration of poorly-water soluble drugs

Allitridi Inhibits Multiple Cardiac Potassium Channels Expressed in HEK 293 Cells

published_or_final_versio

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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

Discrete element modelling and cavity expansion analysis of cone penetration testing

This paper uses the discrete element method (DEM) in three dimensions to simulate cone penetration testing (CPT) of granular materials in a calibration chamber. Several researchers have used different numerical techniques such as strain path methods and finite element methods to study CPT problems. The DEM is a useful alternative tool for studying cone penetration problems because of its ability to provide micro mechanical insight into the behaviour of granular materials and cone penetration resistance. A 30° chamber segment and a particle refinement method were used for the simulations. Giving constant mass to each particle in the sample was found to reduce computational time significantly, without significantly affecting tip resistance. The effects of initial sample conditions and particle friction coefficient on tip resistance are investigated and found to have an important effect on the tip resistance. Biaxial test simulations using DEM are conducted to obtain the basic granular material properties for obtaining CPT analytical solutions based on continuum mechanics. Macro properties of the samples for different input micro parameters are presented and used to obtain the analytical CPT results. Comparison between the numerical simulations and analytical solutions show good agreement

Analysis of bolted flanged panel joint for GRP sectional tanks

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