Dual Functional Antibacterial-Antioxidant Core/Shell Alginate/Poly(ε-caprolactone) Nanofiber Membrane: A Potential Wound Dressing.

Core/shell nanofibers offer the advantage of encapsulating multiple drugs with different hydrophilicity in the core and shell, thus allowing for the controlled release of pharmaceutic agents. Specifically, the burst release of hydrophilic drugs from such fiber membranes causes an instantaneous high drug concentration, whereas a long and steady release is usually desired. Herein, we tackle the problem of the initial burst release by the generation of core/shell nanofibers with the hydrophilic antibiotic drug gentamycin loaded within a hydrophilic alginate core surrounded by a hydrophobic shell of poly(ε-caprolactone).

2D foam film coating of antimicrobial lysozyme amyloid fibrils onto cellulose nanopapers.

Amyloid fibrils made from inexpensive hen egg white lysozyme (HEWL) are bio-based, bio-degradable and bio-compatible colloids with broad-spectrum antimicrobial activity, making them an attractive alternative to existing small-molecule antibiotics. Their surface activity leads to the formation of 2D foam films within a loop, similar to soap films when blowing bubbles. The stability of the foam was optimized by screening concentration and pH, which also revealed that the HEWL amyloid foams were actually stabilized by unconverted peptides unable to undergo amyloid self-assembly rather than the fibrils themselves.

Ibuprofen-loaded electrospun poly(ethylene--vinyl alcohol) nanofibers for wound dressing applications.

Chronic wounds are characterized by a prolonged inflammation phase preventing the normal processes of wound healing and natural regeneration of the skin. To tackle this issue, electrospun nanofibers, inherently possessing a high surface-to-volume ratio and high porosity, are promising candidates for the design of anti-inflammatory drug delivery systems. In this study, we evaluated the ability of poly(ethylene--vinyl alcohol) nanofibers of various chemical compositions to release ibuprofen for the potential treatment of chronic wounds.

Spironolactone alleviates schizophrenia-related reversal learning in Tcf4 transgenic mice subjected to social defeat.

Cognitive deficits are a hallmark of schizophrenia, for which no convincing pharmacological treatment option is currently available. Here, we tested spironolactone as a repurposed compound in Tcf4 transgenic mice subjected to psychosocial stress. In this '2-hit' gene by environment mouse (GxE) model, the animals showed schizophrenia-related cognitive deficits.

Emulsion electrospinning of sodium alginate/poly(ε-caprolactone) core/shell nanofibers for biomedical applications.

Electrospun nanofibers have shown great potential as drug vehicles and tissue engineering scaffolds. However, the successful encapsulation of multiple hydrophilic/hydrophobic therapeutic compounds is still challenging. Herein, sodium alginate/poly(ε-caprolactone) core/shell nanofibers were fabricated water-in-oil emulsion electrospinning.

Wicking fingering in electrospun membranes.

Pronounced fingering of the waterfront is observed for in-plane wicking in thin, aligned electrospun fibrous membranes. We hypothesize that a perturbation in capillary pressure triggers the onset of fingering, which grows in a non-local manner based on the waterfront gradient. Vertical and horizontal wicking in thin electrospun membranes of poly(ethylene--vinyl alcohol) (EVOH) fibers with varying fiber alignment and degree of orientation is studied with backlight photography.

Tailoring Fibre Structure Enabled by X-ray Analytics for Targeted Biomedical Applications.

The rising interest in designing fibres via spinning techniques combining the properties of various polymeric materials into advanced functionalised materials is directed towards targeted biomedical applications such as drug delivery, wearable sensors or tissue engineering. Understanding how these functional polymers exhibit multiscale structures ranging from the molecular level to nano-, micro-and millimetre scale is a key prerequisite for their challenging applications that can be addressed by a non-destructive X-ray based analytical approach. X-ray multimodalities combining X-ray imaging, scattering and diffraction allow the study of morphology, molecular structure, and the analysis of nano-domain size and shape, crystallinity and preferential orientation in 3D arrangements.

Understanding multiscale structure-property correlations in PVDF-HFP electrospun fiber membranes by SAXS and WAXS.

Electrospinning is a versatile technique to produce nanofibrous membranes with applications in filtration, biosensing, biomedical and tissue engineering. The structural and therefore physical properties of electrospun fibers can be finely tuned by changing the electrospinning parameters. The large parameter window makes it challenging to optimize the properties of fibers for a specific application.

pH-Responsive Chitosan/Alginate Polyelectrolyte Complexes on Electrospun PLGA Nanofibers for Controlled Drug Release.

The surface functionalization of electrospun nanofibers allows for the introduction of additional functionalities while at the same time retaining the membrane properties of high porosity and surface-to-volume ratio. In this work, we sequentially deposited layers of chitosan and alginate to form a polyelectrolyte complex via layer-by-layer assembly on PLGA nanofibers to introduce pH-responsiveness for the controlled release of ibuprofen. The deposition of the polysaccharides on the surface of the fibers was revealed using spectroscopy techniques and ζ-potential measurements.

Chemotaxis of T-cells after infection of human choroid plexus papilloma cells with Echovirus 30 in an in vitro model of the blood-cerebrospinal fluid barrier.

Enterovirus is the most common pathogen causing viral meningitis especially in children. Besides the blood-brain barrier (BBB) the choroid plexus, which forms the blood-cerebrospinal-fluid (CSF) barrier (BCSFB), was shown to be involved in the pathogenesis of enteroviral meningitis. In a human in vitro model of the BCSFB consisting of human choroid plexus papilloma cells (HIBCPP), the permissiveness of plexus epithelial cells for Echovirus 30 (EV30) was analyzed by immunoblotting and quantitative real-time PCR (Q-PCR).

Pharmacokinetics of cefotiam in humans.

After intravenous bolus injections of 0.5, 1, and 2 g of cefotiam to three healthy volunteers, the mean (+/- standard deviation) total plasma clearances measured for each dose were, respectively, 26.8 +/- 2.

Investigation of drug absorption from the gastrointestinal tract of man. I. Metoprolol in the stomach, duodenum and jejunum.

Gastrointestinal (GI) absorption of the beta-adrenoceptor blocker metoprolol was investigated in five healthy subjects by means of an intubation method, employing a triple-lumen tube introduced into the intestine, and a twin-lumen tube in the stomach. Metoprolol was introduced into the stomach with a homogenized meal containing a nonabsorbable marker, [14C]-PEG 4000, and another marker, PEG 4000, was perfused continuously into the duodenum just below the pylorus. Samples of GI contents were collected at regular intervals over 4 h in the stomach and at two different levels in the upper small intestine.

Influence of food on the absorption of metoprolol administered as an Oros drug delivery system to man.

The influence of food on the release, absorption and metabolism of metoprolol has been studied after single administration of a 19/190 Oros system to eight healthy volunteers on four occasions, once after an overnight fast, and just before each of three daily meals (breakfast, lunch and dinner). The plasma concentration-time profiles under the four test conditions were virtually identical, and no statistically significant differences in mean areas under the curves between 0 and 32 h, peak concentrations, or times to peak, were detected. The absorption of metoprolol was unaffected by food intake, with 80-90% of the amount absorbed reaching the systemic circulation within 10 h.

Investigation of drug absorption from the gastrointestinal tract of man. V. Effect of the beta-adrenoceptor antagonist, metoprolol, on postprandial gastric function.

The role of the adrenergic system in normal gastric function was assessed in five healthy volunteers by measuring gastric secretion and emptying after a mixed meal containing a non-absorbable marker, [14C]-PEG 4000, with and without 100 mg of metoprolol, a beta 1-adrenoceptor antagonist. Intraduodenal perfusion of PEG 4000, and gastric and jejunal sampling was achieved by means of a gastrointestinal intubation technique. Gastric function was assessed from the degree of dilution of the duodenal marker.

Investigation of drug absorption from the gastrointestinal tract of man. IV. Influence of food and digestive secretions on metoprolol jejunal absorption.

The influence of nutrients and digestive secretions on the intestinal absorption and bioavailability of the beta-adrenoceptor antagonist, metoprolol, was investigated in an isolated segment of jejunum using an intestinal perfusion technique. Two solutions containing metoprolol, one with, and one without nutrients, were perfused into the jejunum with an occluding balloon inflated or deflated. Jejunal fluid, blood and urine samples were then collected for drug or metabolite estimation.

Investigation of drug absorption from the gastrointestinal tract of man. III. Metoprolol in the colon.

The colonic absorption of metoprolol was indirectly evaluated by measuring drug appearance in plasma following intravenous, jejunal or colonic infusion in six healthy volunteers. Plasma concentrations of alpha-hydroxymetoprolol and urinary excretion of the main metabolites were also measured. Plasma profiles of metoprolol after colonic and jejunal perfusion were similar, and the relative bioavailabilities of the drug from these two regions of the gut were not significantly different.

Investigation of drug absorption from the gastrointestinal tract of man. II. Metoprolol in the jejunum and ileum.

Absorption of metoprolol in jejunum and ileum was investigated in eight healthy subjects using an intestinal perfusion technique below an occlusive balloon. An isotonic saline solution, with or without metoprolol, was perfused at a flow rate of 10 ml/min, either at the angle of Treitz or in the middle part of the ileum. The absorption in a 30 cm intestinal segment was evaluated at metoprolol concentrations of 20, 40 and 60 mg/l.

Oxprenolol placental transfer, plasma concentrations in newborns and passage into breast milk.

Thirty-two pregnant hypertensive patients were treated with oxprenolol administered in combination with dihydralazine as Trasipressol tablets. Before delivery, oxprenolol was demonstrable in the maternal plasma and the amniotic fluid. The free fraction of oxprenolol in the maternal serum (15% +/- 7.

Pharmacokinetics of cefotiam and cefsulodin after simultaneous administration to patients with impaired renal function.

The possible influence of the concomitant administration of cefotiam and cefsulodin on their respective pharmacokinetics was studied in 15 patients with renal insufficiency and 10 anuric patients. Linear relations were found between the clearance of creatinine and the total clearance, as well as the renal clearance, of each drug. These relations for each cephalosporin were not significantly different from previous results obtained after separate administration.

Pharmacokinetics and dosage adjustment of cefotiam in renal impaired patients.

The pharmacokinetics of cefotiam were investigated after intravenous administration of 1 g to 2 healthy volunteers with normal renal function and to 16 patients whose creatinine clearance ranged from 4.7 to 0.1 l/h (78 to 1.

[Comparative elimination of pirprofen from the plasma and synovial fluid of the knee. 26 cases].

Twenty-six patients with various inflammatory diseases of the knee were treated with a 400 mg dose of pirprofen orally twice a day for 2 days. On the third day, samples of blood and synovial fluid were taken 3 h and 10 h approximately after a fifth 400 mg dose of the drug. Pirprofen concentrations, as determined by gas-liquid chromatography, were higher in plasma than in synovial fluid during the 2-5 h period post-dosing.