Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process

This study reports on novel fast-dissolving core-shell composite microparticles of quercetin fabricated using coaxial electrospraying. A PVC-coated concentric spinneret was developed to conduct the electrospray process. A series of analyses were undertaken to characterize the resultant particles in terms of their morphology, the physical form of their components, and their functional performance. Scanning and transmission electron microscopies revealed that the microparticles had spherical morphologies with clear core-shell structure visible. Differential scanning calorimetry and X-ray diffraction verified that the quercetin active ingredient in the core and sucralose and sodium dodecyl sulfate (SDS) excipients in the shell existed in the amorphous state. This is believed to be a result of second-order interactions between the components; these could be observed by Fourier transform infrared spectroscopy. In vitro dissolution and permeation studies showed that the microparticles rapidly released the incorporated quercetin within one minute, and had permeation rates across the sublingual mucosa around 10 times faster than raw quercetin

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

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

Nonparametric dynamical model of cardiorespiratory responses at the onset and offset of treadmill exercises

© 2018, International Federation for Medical and Biological Engineering. This paper applies a nonparametric modelling method with kernel-based regularization to estimate the carbon dioxide production during jogging exercises. The kernel selection and regularization strategies have been discussed; several commonly used kernels are compared regarding the goodness-of-fit, sensitivity, and stability. Based on that, the most appropriate kernel is then selected for the construction of the regularization term. Both the onset and offset of the jogging exercises are investigated. We compare the identified nonparametric models, which include both impulse response models and step response models for the two periods, as well as the relationship between oxygen consumption and carbon dioxide production. The result statistically indicates that the steady-state gain of the carbon dioxide production in the onset of exercise is bigger than that in the offset while the response time of both onset and offset are similar. Compared with oxygen consumption, the response speed of carbon dioxide production is slightly slower in both onset and offset period while its steady-state gains are similar for both periods. The effectiveness of the kernel-based method for the dynamic modelling of cardiorespiratory response to exercise is also well demonstrated. [Figure not available: see fulltext.]

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

Electrospun Janus nanofibers loaded with a drug and inorganic nanoparticles as an effective antibacterial wound dressing

The most important property of a wound dressing is its anti-bacteria performance. Although electrospun nanofibers are frequently demonstrated to be potent candidates as wound dressings, no Janus fibers have been explored for this popular application. In this study, a Janus wound dressing composed of polyvinylpyrrolidone (PVP) and ethyl cellulose (EC) polymer matrices was prepared via a side-by-side electrospinning process, in which ciprofloxacin (CIP) and silver nanoparticles (AgNPs) were loaded in the two sides. A homemade acentric spinneret was exploited to maintain a continuous preparation process. Scanning and transmission electron microscope results demonstrated that the Janus fibers had a uniform and cylindrical morphology with a clear Janus structure, and AgNPs distributed in one side. X-ray diffraction patterns suggested that drug was present in the fibers in an amorphous state owing to rapid drying and its good compatibility with PVP, which was verified by infrared spectroscopy. In vitro tests showed that over 90% of CIP was released within the first 30 min, ensuring a strong antibacterial effect at the initial stages of wound healing. The Janus fibers were demonstrated to have good bactericidal activity against the growth of both Gram-positive S. aureus and Gram-negative E. coli. The PVP-CIP/EC-AgNPs Janus fibers could thus be a promising candidate for effective wound dressings. This work paves a new way for creating Janus structure-based advanced functional nanomaterials

Multifunctional fabrics finished using electrosprayed hybrid Janus particles containing nanocatalysts

There is great market demand for fabrics equipped with multiple functionalities. However, most methods to impart these properties to a pristine fabric are complicated, time-consuming, and expensive. In this work, Janus particles with one side comprising TiO2 nanoparticles (NPs)-PVDF (poly (vinylidene fluoride)) and the other an epoxy resin (TPE) were deposited on a fabric surface. The aim was to endow the fabric with the superhydrophobic, UV resistance, and antimicrobial properties. The Janus particles were firmly attached to the fabrics through the adhesion effects of the epoxy resin. Characterization by XRD, SEM, EDX, and FTIR verified the successful finishing of the fabric with TPE particles. The ultraviolet protection factor increased from 7.86 for the pristine fabric to 733 after finishing. The finished fabric also exhibited superhydrophobic properties, with a water contact angle of 152°. Further, the coating of the fabric did not hamper its gas permeability. Potent antibacterial properties against E. coli were observed owing to the antibacterial properties of TiO2 under pre-irradiation by UV light. The protocols reported here provide a new platform for the nano-finishing of fabrics, allowing new functions to be imparted without compromising

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

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