Ensayo aleatorizado del cierre de orejuela izquierda vs varfarina para la prevención de accidentes cerebrovasculares tromboembólicos en pacientes con fibrilación auricular no relacionada con valvulopatía. Estudio PREVAIL

The successful application of poly­(<i>N</i>-vinylcaprolactam)-based microgels requires a profound understanding of their synthesis. For this purpose, a validated process model for the microgels synthesis by precipitation copolymerization with the cross-linker <i>N</i>,<i>N</i>′-methylenebis­(acrylamide) is formulated. Unknown reaction rate constants, reaction enthalpies, and partition coefficients are obtained by quantum mechanical calculations. The remaining parameter values are estimated from reaction calorimetry and Raman spectroscopy measurements of experiments with different monomer/cross-linker compositions. Because of high cross-propagation reaction rate constants, simulations predict a fast incorporation of the cross-linker. This agrees with reaction calorimetry measurements. Furthermore, the gel phase is predicted as the major reaction locus. The model is utilized for a prediction of the internal particle structure regarding its cross-link distribution. The highly cross-linked core reported in the literature corresponds to the predictions of the model

Reversible Switching and Recycling of Adaptable Organic Microgel Catalysts (Microgelzymes) for Asymmetric Organocatalytic Desymmetrization

Adaptable enzyme-mimetic catalysts based on temperature-responsive polymer microgels (microgelzymes) have been developed. By a simple change in the temperature, a microgel catalyst can be reversibly switched into its soluble or precipitated form, thus combining the advantages of homogeneous and heterogeneous catalysis. The responsive microgel reactors show high reactivity and selectivity, as well as good recycling properties in the alcoholysis of <i>cis</i>-tetrahydrophthalic anhydride

Surfactant-Free Synthesis of Polystyrene Nanoparticles Using Oligoglycidol Macromonomers

We investigate the synthesis of functional polystyrene/oligoglycidol particles by surfactant-free emulsion polymerization. Oligoglycidol macromonomers with linear and branched oligoglycidol structure and variable oligoglycidol chain lengths were synthesized. These macromonomers were used as surfmers (surfactants and comonomers) in emulsion polymerization of styrene. Monodisperse colloidally stable polystyrene particles were obtained, decorated with oligoglycidol chains with diameters between 100 and 600 nm. The increase of the macromonomer concentration induced a decrease of the particle size and broadening of the particle size distribution. The macromonomers with branched architecture were more effective and produced monodisperse particles even at low concentrations. Due to the steric stabilization provided by the hydrophilic oligoglycidol layer on the particle surface, the emulsion of polystyrene/oligoglycidol particles obtained exhibited very good resistance against electrolytes. The chemical and enzyme catalyzed grafting polymerization of ε-caprolactone from the polystyrene/oligoglycidol particle surface was demonstrated along with formation of composite particles

Microgel-Based Adaptive Hybrid Capsules with Tunable Shell Permeability

In the present work, we demonstrate the preparation of adaptive hybrid capsules with microgel/SiO₂ composite walls. During the first stage of the capsule synthesis process, microgel particles stabilize the oil droplets in water and become self-assembled on the oil/water interface. At the second stage, microgels are subsequently glued by the sol–gel reaction of a silica precursor-hyperbranched polyethoxysiloxane (PEOS) which occurs at the oil/water interface. Consequently, hybrid capsules consisting of silica shell with embedded microgels are obtained. Responsive microgels present in the capsule wall act as transportation channels for different encapsulated materials. The use of smart microgels allows us to design capsules with controlled size, morphology, and wall permeability able to operate in both water and organic solvents

Correlated Morphological Changes in the Volume Temperature Transition of Core–Shell Microgels

PVCL and PNIPMAAm core–shell components in microgel particles are shown to have different volume phase temperature transition behavior than the respective homopolymer microgel particles due to confinement effects. A combination of dynamic light scattering (DLS) data that gives access to the temperature dependence of hydrodynamic radius and modified Flory–Rehner theory in the presence of networks confinement allowed obtaining information about correlated morphological changes of components inside of core–shell microgels. The core–shell components individual temperature behavior is analyzed by modifying the Flory–Rehner transition theory in order to account for core–shell morphology and the existence of an interaction force between core and shell. Describing the dependence on temperature of the radial scale parameter, the ratio between the radius of the core and the hydrodynamic radius, we gain access to the swelling behavior of the core and shell components irrespective of the swelling behavior of the total hydrodynamic radius. Furthermore, the theoretical description of volume phase temperature transition permits the development of scenarios for the correlated changes in the core and shell radial dimensions for the two microgels with reversed morphologies. The fact that the theoretical model is appropriate for the treatment of core–shell microgels is proved <i>a posteriori</i> by obtaining a temperature dependence of the components that is in accordance with the expected physical behavior. Novel core–shell microgel systems of PVCL (poly­(<i>N</i>-vinylcaprolactam))-core/PNIPMAAm (poly­(<i>N</i>-isopropylmethacrylamide))-shell and PNIPMAAm-core/PVCL-shell, with a double volume phase temperature transition due to the thermoresponsive components, were used for this study

Electrostatic Interactions and Osmotic Pressure of Counterions Control the pH-Dependent Swelling and Collapse of Polyampholyte Microgels with Random Distribution of Ionizable Groups

In this work, different systems of colloidally stable, ampholytic microgels (μGs) based on poly­(<i>N</i>-vinyl­capro­lactam) and poly­(<i>N</i>-isopropyl­acryl­amide), wherein the anionic and cationic groups are randomly distributed, were investigated. Fourier transmission infrared spectroscopy and transmission electron microscopy confirmed the quantitative incorporation and random distribution of ionizable groups in μGs, respectively. The control of hydrodynamic radii and mechanical properties of polyampholyte μGs at different pH values was studied with dynamic light scattering and in situ atomic force microscopy. We have proposed a model of pH-dependent polyampholyte μG, which correctly describes the experimental data and explains physical reasons for the swelling and collapse of the μG at different pHs. In the case of a balanced μG (equal numbers of cationic and anionic groups), the size as a function of pH has a symmetric, V-like shape. Swelling of purely cationic μG at low pH or purely anionic μG at high pH is due to electrostatic repulsion of similarly charged groups, which appears as a result of partial escape of counterions. Also, osmotically active counterions (the counterions that are trapped within the μG) contribute to the swelling of the μG. In contrast, electrostatic interactions are responsible for the collapse of the μG at intermediate pH when the numbers of anionic and cationic groups are equal (stoichiometric ratio). The multipole attraction of the charged groups is caused by thermodynamic fluctuations, similar to the those observed in Debye–Hückel plasma. We have demonstrated that the higher the fraction of cationic and anionic groups, the more pronounced the swelling and collapse of the μG at different pHs

Gadolinium-Loaded Poly(<i>N</i>‑vinylcaprolactam) Nanogels: Synthesis, Characterization, and Application for Enhanced Tumor MR Imaging

We report the synthesis of poly­(<i>N</i>-vinylcaprolactam) nanogels (PVCL NGs) loaded with gadolinium (Gd) for tumor MR imaging applications. The PVCL NGs were synthesized via precipitation polymerization using the monomer <i>N</i>-vinylcaprolactam (VCL), the comonomer acrylic acid (AAc), and the degradable cross-linker 3,9-divinyl-2,4,8,10-tetraoxaspiro-[5,5]-undecane (VOU) in aqueous solution, followed by covalently binding with 2,2′,2″-(10-(4-((2-aminoethyl)­amino)-1-carboxy-4-oxobutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (NH₂-DOTA-GA)/Gd complexes. We show that the formed Gd-loaded PVCL NGs (PVCL-Gd NGs) having a size of 180.67 ± 11.04 nm are water dispersible, colloidally stable, uniform in size distribution, and noncytotoxic in a range of the studied concentrations. The PVCL-Gd NGs also display a r₁ relaxivity (6.38–7.10 mM^–1 s^–1), which is much higher than the clinically used Gd chelates. These properties afforded the use of the PVCL-Gd NGs as an effective positive contrast agent for enhanced MR imaging of cancer cells in vitro as well as a subcutaneous tumor model in vivo. Our study suggests that the developed PVCL-Gd NGs could be applied as a promising contrast agent for <i>T</i>₁-weighted MR imaging of diverse biosystems

Das Susac Syndrom - Mikroangiopathie als seltene Ursache bilateraler Taubheit

We report on the behavior of two immiscible liquids within polymer microgel adsorbed at their interface. By means of dissipative particle dynamics (DPD) simulations and theoretical analysis in the framework of the Flory–Huggins (FH) lattice theory, we demonstrate that the microgel acts as a “compatibilizer” of these liquids: their miscibility within the microgel increases considerably. If the incompatibility of the liquids is moderate, although strong enough to induce phase separation in their 1:1 composition, they form homogeneous mixture in the microgel interior. The mixture of highly incompatible liquids undergoes separation into two (micro)­phases within the microgel likewise out of it; however, the segregation regime is weaker and the concentration profiles are characterized by a weaker decay (gradient) in comparison with those of two pure liquids. The enhanced miscibility is a result of the screening of unfavorable interactions between unlike liquid molecules by polymer subchains. We have shown that better miscibility of the liquids is achieved with densely cross-linked microgels. Our findings are very perspective for many applications where immiscible species have to be mixed at interfaces (like in heterogeneous catalysis)

Monitoring the Internal Structure of Poly(<i>N</i>‑vinylcaprolactam) Microgels with Variable Cross-Link Concentration

The combination of a set of complementary techniques allows us to construct an unprecedented and comprehensive picture of the internal structure, temperature dependent swelling behavior, and the dependence of these properties on the cross-linker concentration of microgel particles based on <i>N</i>-vinylcaprolactam (VCL). The microgels were synthesized by precipitation polymerization using different amounts of cross-linking agent. Characterization was performed by small-angle neutron scattering (SANS) using two complementary neutron instruments to cover a uniquely broad Q-range with one probe. Additionally we used dynamic light scattering (DLS), atomic force microscopy (AFM), and differential scanning calorimetry (DSC). Previously obtained nuclear magnetic resonance spectroscopy (NMR) results on the same PVCL particles are utilized to round the picture off. Our study shows that both the particle radius and the cross-link density and therefore also the stiffness of the microgels rises with increasing cross-linker content. Hence, more cross-linker reduces the swelling capability distinctly. These findings are supported by SANS and AFM measurements. Independent DLS experiments also found the increase in particle size but suggest an unchanged cross-link density. The reason for the apparent contradiction is the indirect extraction of the parameters via a model in the evaluation of DLS measurements. The more direct approach in AFM by evaluating the cross section profiles of observed microgel particles gives evidence of significantly softer and more deformable particles at lower cross-linker concentrations and therefore verifies the change in cross-link density. DSC data indicate a minor but unexpected shift of the volume phase transition temperature (VPTT) to higher temperatures and exposes a more heterogeneous internal structure of the microgels with increasing cross-link density. Moreover, a change in the total energy transfer during the VPT gives evidence that the strength of hydrogen bonds is significantly affected by the cross-link density. A strong and reproducible deviation of the material density of the cross-linked microgel polymer chains toward a higher value compared to the respective linear chains has yet to be explained

Swelling of a Responsive Network within Different Constraints in Multi-Thermosensitive Microgels

We report on the swelling of a polymeric network in doubly thermoresponsive microgels. Silica-core double-shell and hollow double-shell microgels made of an inner poly­(<i>N</i>-isopropyl­methacrylamide) and an outer poly­(<i>N</i>-isopropyl­acrylamide) shell are studied by exploiting the distinct temperature sensitivities of the polymers. The swelling states of the two shells can be tuned by temperature changes enabling three different swelling states: above, below, and between the distinct volume phase transition temperatures of the two polymers. This enables to investigate the effect of different constraints on the swelling of the inner network. Small-angle neutron scattering with contrast variation in combination with computer simulation discloses how the expansion of the inner shell depends on the material and swelling state of its constraints. In the presence of the stiff core, the microgels show a considerable interpenetration of the polymeric shells: the inner network expands into the outer deswollen shell. This interpenetration vanishes when the outer network is swollen. Furthermore, as predicted by our computer simulations, an appropriate choice of cross-linking density enables the generation of hollow double-shell nanocapsules. Here, the inner shell undergoes a <i>push–pull effect</i>. At high temperature, the collapsed outer shell pushes the swollen inner network into the cavity. At lower temperature, the swelling of the outer network contrary pulls the inner shell back toward the external periphery