Unlocking the potential of biocompatible chitosan-hyaluronic acid nanogels labeled with fluorochromes: A promising step toward enhanced FRET bioimaging.

Chitosan is a natural polysaccharide widely used in medical formulations as nanoparticles due to their special properties. Our work aimed to assess the biocompatibility of chitosan-hyaluronic acid nanogels labeled with fluorochromes for use in biomedical applications, based on the FRET effect. The preparation method included the ionic gelation, grafting rhodamine or fluorescein isothiocyanate molecules onto the chitosan backbone.

In Vivo Evaluation of Innovative Gadolinium-Based Contrast Agents Designed for Bioimaging Applications.

The aim of this study was the investigation of biochemical and histological changes induced in different tissues, as a result of the subcutaneous administration of Gd nanohydrogels (GdDOTA⸦CS-TPP/HA) in a CD-1 mouse strain. The nanohydrogels were obtained by encapsulating contrast agents (GdDOTA) in a biocompatible polymer matrix composed of chitosan (CS) and hyaluronic acid (HA) through the ionic gelation process. The effects of Gd nanohydrogels on the redox status were evaluated by measuring specific activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as oxidative stress markers, such as reduced glutathione (GSH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), and protein-reactive carbonyl groups (PRCG), in the liver, kidney, and heart tissues.

In Vitro Studies Regarding the Safety of Chitosan and Hyaluronic Acid-Based Nanohydrogels Containing Contrast Agents for Magnetic Resonance Imaging.

The aim of this study was to investigate the biocompatibility of contrast agents, such as gadolinium 1, 4, 7, 10 tetraazacyclo-dodecane tetraacetic acid (GdDOTA) and gadolinium dioctyl terephthalate (GdDOTP), encapsulated in a polymeric matrix containing chitosan and hyaluronic acid using RAW264.7 murine macrophages and human blood samples. The cell viability and cytotoxicity were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, while cell cycle analysis was determined in RAW264.

Synthesis and Characterization of Conjugated Hyaluronic Acids. Application to Stability Studies of Chitosan-Hyaluronic Acid Nanogels Based on Fluorescence Resonance Energy Transfer.

Hyaluronic acid (HA) was functionalized with a series of amino synthons (octylamine, polyethylene glycol amine, trifluoropropyl amine, rhodamine). Sodium hyaluronate (HAs) was first converted into its protonated form (HAp) and the reaction was conducted in DMSO by varying the initial ratio (-NH (synthon)/COOH (HAp)). HA derivatives were characterized by a combination of techniques (FTIR, H NMR, 1D diffusion-filtered F NMR, DOSY experiments), and degrees of substitution (DS) varying from 0.

Targeting Ovarian Carcinoma with TSP-1:CD47 Antagonist TAX2 Activates Anti-Tumor Immunity.

TAX2 peptide is a cyclic peptide that acts as an orthosteric antagonist for thrombospondin-1 (TSP-1) interaction with CD47. TAX2 was first described for its anti-angiogenic activities and showed anti-cancer efficacy in numerous preclinical models. Here, we aimed at providing an extensive molecular characterization of TAX2 mode of action, while evaluating its potential in ovarian cancer therapy.

Investigation of squalene-doxorubicin distribution and interactions within single cancer cell using Raman microspectroscopy.

Intracellular distribution of doxorubicin (DOX) and its squalenoylated (SQ-DOX) nanoparticles (NPs) form in murine lung carcinoma M109 and human breast carcinoma MDA-MB-231 cells was investigated by Raman microspectroscopy. Pharmacological data showed that DOX induced higher cytotoxic effect than SQ-DOX NPs. Raman data were obtained using single-point measurements and imaging on the whole cell areas.

Transmembrane Peptides as a New Strategy to Inhibit Neuraminidase-1 Activation.

Sialidases, or neuraminidases, are involved in several human disorders such as neurodegenerative, infectious and cardiovascular diseases, and cancers. Accumulative data have shown that inhibition of neuraminidases, such as NEU1 sialidase, may be a promising pharmacological target, and selective inhibitors of NEU1 are therefore needed to better understand the biological functions of this sialidase. In the present study, we designed interfering peptides (IntPep) that target a transmembrane dimerization interface previously identified in human NEU1 that controls its membrane dimerization and sialidase activity.

Evaluation of mTHPC-loaded PLGA nanoparticles for in vitro photodynamic therapy on C6 glioma cell line.

Photodynamic therapy (PDT) is a very attractive strategy to complement or replace common cancer treatments such as radiotherapy, surgery, and chemotherapy. Some molecules have shown their efficiency as photosensitizers (PS), still many issues have to be solved such as the inherent cytotoxicity of the PS or its hydrophobic properties causing limitation in their solubility, leading to side effects. In this study, the encapsulation of an approved PS, the meso-tetra hydroxyphenylchlorine (mTHPC, Foscan®) within biocompatible and biodegradable poly(D, l-lactide-co-glycolide) acid (PLGA) NPs prepared by the nanoprecipitation method was studied.

Biocompatibility of Gd-Loaded Chitosan-Hyaluronic Acid Nanogels as Contrast Agents for Magnetic Resonance Cancer Imaging.

Although the research on nanogels incorporating Gd chelates for theranostic applications has grown exponentially in recent years, knowledge about their biocompatibility is limited. We compared the biocompatibility of Gd-loaded hyaluronic acid-chitosan-based nanogels (GdCA⊂CS-TPP/HA) with two chitosan concentrations (2.5 and 1.

Synthesis and Characterization of PEGylated and Fluorinated Chitosans: Application to the Synthesis of Targeted Nanoparticles for Drug Delivery.

To synthesize chitosan nanoparticles (CS NPs), ionic gelation is a very attractive method. It relies on the spontaneous supramolecular assembly of cationic CS with anionic compounds, which leads to nanohydrogels. To extend ionic gelation to functionalized CS, the assessment of CS degree of substitution (DS) is a key step.

Tribute to Dr Jacques Rogge: muscle activity and fatigue during hiking in Olympic dinghy sailing.

'A tribute to Dr J. Rogge' aims to systematically review muscle activity and muscle fatigue during sustained submaximal quasi-isometric knee extension exercise (hiking) related to Olympic dinghy sailing as a tribute to Dr Rogge's merits in the world of sports. Dr Jacques Rogge is not only the former President of the International Olympic Committee, he was also an orthopaedic surgeon and a keen sailor, competing at three Olympic Games.

Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI).

Chitosan CS-tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8).

Detailed kinetic performance analysis of micromachined radially elongated pillar array columns for liquid chromatography.

The individual factors that determine the kinetic performance (B- and C-term band broadening and bed permeability Kv) of radially elongated pillar (REP) columns are studied. To this end, columns with REPs having 4 different aspect ratios (AR=9, 12, 15, 20) were characterized experimentally and by means of numerical simulations. A tortuosity and retention based plate height equation was established, enabling a good global fit for all studied conditions.

Mass-manufacturable polymer microfluidic device for dual fiber optical trapping.

We present a microfluidic chip in Polymethyl methacrylate (PMMA) for optical trapping of particles in an 80µm wide microchannel using two counterpropagating single-mode beams. The trapping fibers are separated from the sample fluid by 70µm thick polymer walls. We calculate the optical forces that act on particles flowing in the microchannel using wave optics in combination with non-sequential ray-tracing and further mathematical processing.

Merging Open-Tubular and Packed Bed Liquid Chromatography.

Experimental and theoretical proof is provided for the fact that a microfabricated packed bed column, which is uniformly filled with radially elongated pillars (REPs), can produce the same separation performance as nonpacked, open-tubular columns. These are generally recognized as the best possible chromatographic column format, offering the highest conceivable separation speed and efficiency. It is also demonstrated both experimentally and theoretically that, as long as pressure is not a limiting factor, the REP column format can even outperform the open-tubular column format, with significant gains in either speed or efficiency proportional to the tortuosity, τ, of the bed.

Assessment and numerical search for minimal Taylor-Aris dispersion in micro-machined channels of nearly rectangular cross-section.

A mathematical procedure using the Matlab® PDE toolbox to calculate the numerical constant appearing in the general Taylor-Aris expression for the dispersion in a laminar flow through open-tubular conduits with a variety of quasi-rectangular cross-sectional shapes is described. The procedure has been applied to assess the effect of some of the most frequently occurring etching imperfections (linear or curved tapering of the inter-pillar distance along the depth coordinate, occurrence of local notches) in etched pillar array columns. In addition, covering a broad range of possible geometries, a number of new shapes and optimal geometries to minimize the dispersion in open-tubular microchannels and pillar array columns have been proposed.

Suppression of the sidewall effect in pillar array columns with radially elongated pillars.

An important bottleneck of pillar array columns designed for liquid chromatography is that small deviations of the target 'magical distance' at the sidewall region leads to detrimental sidewall effects, due to local differences of linear velocities at the sidewall region versus other locations in the pillar bed. In the present study, we demonstrate that a lateral elongation of the pillar significantly increases the tolerance for offsets of the magical distance. By shifting the sidewall distance 600 nm for 2 pillar aspect ratio (AR) designs (AR=3 and 9), only minor sidewall effects on the measured plate heights could be observed for the AR=9 columns, while the plate height was roughly doubled when using the wrong versus the correct sidewall distance for the AR=3 columns.

Tuning the composition of biocompatible Gd nanohydrogels to achieve hypersensitive dual T/T MRI contrast agents.

A series of hydrogel nanoparticles incorporating MRI contrast agents (GdDOTP and MS325) as potential cross-linkers were elaborated by an easy and robust ionotropic gelation process. By this process, high Gd loadings were obtained (between 1.8 and 14.

Integration of uniform porous shell layers in very long pillar array columns using electrochemical anodization for liquid chromatography.

Electrochemical anodization has been applied to grow porous shell layers of 300 nm (30 nm pores) in 5 μm diameter pillar array columns (PACs) with a spacing of 2.5 μm. Using turn structures preceded and followed by the flow distributor structures recently introduced by our group and filled with radially elongated pillars, columns with quasi unlimited channel lengths could be conceived.

Biomechanical and physiological demands of kitesurfing and epidemiology of injury among kitesurfers.

Kitesurfing is a relatively new extreme water sport that is considered a high-risk sport and has rising popularity. Kitesurfing combines aspects of several water sports, including surfing, windsurfing, and wakeboarding. With a large controllable kite and a small board, kitesurfers travel over the water surface with speeds of up to 35 knots.

Cardiorespiratory and muscular responses to simulated upwind sailing exercise in Optimist sailors.

The aim of this work was to gain more insight into the cardiorespiratory and muscular (m. vastus lateralis) responses to simulated upwind sailing exercise in 10 high-level male and female Optimist sailors (10.8-14.

On the advantages of radially elongated structures in microchip-based liquid chromatography.

We report on the possibility to realize submicrometer plate heights using chromatographic pillar array columns filled with radially elongated diamond-shaped pillars, even when using a relatively large interpillar distance (2.5 μm) and axial pillar width (5 μm). It is demonstrated that the use of high aspect ratio radially elongated pillars which are 15 times wider in the radial than in the axial direction can lead to a fivefold reduction of the minimal plate height compared to beds filled with pillars with a similar interpillar distance but with an aspect ratio around unity (cylinders and diamonds).

Development of an upwind sailing ergometer.

Purpose: To develop a sailing ergometer that accurately simulates upwind sailing exercise.

Methods: A sailing ergometer that measures roll moment accompanied by a biofeedback system that allows imposing a certain quasi-isometric upwind sailing protocol (ie, 18 bouts of 90-s hiking at constantly varying hiking intensity interspersed with 10 s to tack) was developed. Ten male high-level Laser sailors performed an incremental cycling test (ICT; ie, step protocol at 80 W + 40 W/3 min) and an upwind sailing test (UST).