Copolymerization Kinetics of Dopamine Methacrylamide during PNIPAM Microgel Synthesis for Increased Adhesive Properties.

Combining stimuli-responsive properties of gels with adhesive properties of mussels is highly interesting for a large field of applications as, e.g., in life science. Therefore, the present paper focuses on the copolymerization of poly(N-isopropylacrylamide) (PNIPAM) microgels with dopamine methacrylamide (DMA). A detailed understanding of reaction kinetics is crucial to figure out an optimized synthesis strategy for tailoring microgels with adhesive properties. The present study addresses the influence of relevant synthesis parameters as the injection time of DMA during the microgel synthesis and the overall reaction time of the microgel. Reaction kinetics were studied by mass spectrometry of time samples taken during the microgel synthesis. This allowed us to determine the monomer consumption of NIPAM, the cross-linker N,N'-methylenebisacrylamide (BIS), and DMA. A second-order reaction kinetics was found for DMA incorporation. The amount of DMA incorporated in the resulting microgel was successfully determined by a combination of UV-vis and NMR spectroscopy to level off limitations of both methods. The dependence of the hydrodynamic radius on temperature was determined by DLS measurements for the microgels. While an early injection of DMA stops the PNIPAM polymerization due to scavenging, it greatly enhances the reaction speed of DMA. The faster reaction of DMA and the incomplete NIPAM and BIS conversion also compensate for shorter reaction times with respect to the incorporated amount of DMA. On the contrary, a later injection of DMA leads to a full NIPAM monomer and BIS cross-linker consumption. An overall reaction time of 60 min ensures the DMA incorporation. Longer reaction times lead to clumping. First adhesion tests show an increased adhesion of P(NIPAM-co-DMA) microgels compared to pure PNIPAM microgels, when mechanical stress is applied.

Construction of Compact Polyelectrolyte Multilayers Inspired by Marine Mussel: Effects of Salt Concentration and pH As Observed by QCM-D and AFM.

Biomimetic multilayers based on layer-by-layer (LbL) assembly were prepared as functional films with compact structure by incorporating the mussel-inspired catechol cross-linking. Dopamine-modified poly(acrylic acid) (PAADopa) was synthesized as a polyanion to offer electrostatic interaction with the prelayer polyethylenimine (PEI) and consecutively cross-linked by zinc to generate compact multilayers with tunable physicochemical properties. In situ layer-by-layer growth and cross-linking were monitored by a quartz crystal microbalance with dissipation (QCM-D) to reveal the kinetics of the process and the influence of Dopa chemistry. Addition of Dopa enhanced the mass adsorption and led to the formation of a more compact structure. An increase of ionic strength induced an increase in mass adsorption in the Dopa-cross-linked multilayers. This is a universal approach for coating of various surfaces such as Au, SiO2, Ti, and Al2O3. Roughness observed by AFM in both wet and dry conditions was compared to confirm the compact morphology of Dopa-cross-linked multilayers. Because of the pH sensitivity of Dopa moiety, metal-chelated Dopa groups can be turned into softer structure at higher pH as revealed by reduction of Young's modulus determined by MFP-3D AFM. A deeper insight into the growth and mechanical properties of Dopa-cross-linked polyelectrolyte multilayers was addressed in the present study. This allows a better control of these systems for bioapplications.

Responsive aqueous foams.

Remarkable properties have emerged recently for aqueous foams, including ultrastability and responsiveness. Responsive aqueous foams refer to foams for which the stability can be switched between stable and unstable states with a change in environment or with external stimuli. Responsive foams have been obtained from various foam stabilizers, such as surfactants, proteins, polymers, and particles, and with various stimuli. Different strategies have been developed to design this type of soft material. We briefly review the two main approaches used to obtain responsive foams. The first approach is based on the responsiveness of the interfacial layer surrounding the gas bubbles, which leads to responsive foams. The second approach is based on modifications that occur in the aqueous phase inside the foam liquid channels to tune the foam stability. We will highlight the most sophisticated approaches, which use light, temperature, and magnetic fields and lead to switchable foam stability.

Ethylene glycol-based microgels at solid surfaces: swelling behavior and control of particle number density.

The adsorption of ethylene glycol (EG)-based microgel particles at silicon surfaces was investigated. Monodisperse p-MeO2MA-co-OEGMA microgel particles were synthesized by precipitation polymerization. Particle size and the volume phase transition temperature (VPTT) can be tailored by changing the amount of comonomer. The effect of geometrical confinement on the microgel particles was studied at the solid/liquid interface. Therefore, layer formation, particle number density, and swelling/deswelling at the surface were studied in dependence on the spin-coating preparation parameters and characterized by means of AFM against ambient conditions. The deswelling/swelling behavior was investigated by AFM in the water-swollen state.

Effect of polyelectrolytes on (de)stability of liquid foam films.

The review addresses the influence of polyelectrolytes on the stabilisation of free-standing liquid foam films, which affects the stability of a whole macroscopic foam. Both the composition of the film surface and the stratification of the film bulk drives the drainage and the interfacial forces within a foam film. Beside synthetic polyelectrolytes also natural polyelectrolytes like cellulose, proteins and DNA are considered.

Visualization of real-time degradation of pH-responsive polyglycerol nanogels via atomic force microscopy.

Polyglycerol nanogels (nPG) have a huge impact in biomedical applications as drug deliverer due to their high biocompability. For such nPG nanogels, particle degradation is widely used as drug delivery method. The knowledge of this degradation process is limited up to date. In this communication, a real time visualization of such a degradation process is presented for pH-responsive nPG nanogels via atomic force microscopy (AFM) under ambient and in liquid conditions. The particle height plays a major role in the degradation process and decays exponentially in the beginning of this process. The particle width increases during the process indicating a "decross-linking" step of the particles into their starting monomers. Measurements under ambient conditions confirm this assumption and provide further insight in the "decross-linking" step of the nanogels into individual dendritic particles. The present work gives a detailed insight in the particle degradation process, which is essential for further progress for the development of new drug delivery systems.

A new multiresponsive drug delivery system using smart nanogels.

This paper addresses the synthesis and characterization of a novel temperature- and pH-responsive nanogel system based on poly(vinylcaprolactam-co-2-dimethylaminoethyl methacrylate) [P(VCL-co-DMAEMA)] by using a surfactant-free emulsion polymerization procedure for the multiresponsive drug delivery of hydrophobic drugs. The effects of solvent, monomer, pH, and temperature were studied to tailor the average particle hydrodynamic diameters and the polydispersity index of the final particles. According to dynamic light-scattering measurements, the obtained nanogels show a narrow particle-size distribution and their hydrodynamic diameters can be varied from 81 to 368 nm. The nanogels display a re-entrant phase-transition state, and the equilibrium volume swelling ratio of the nanogels decreases drastically down to 47 °C and then increases up to 65 °C. In addition, the nanogels show pH-dependent behavior. They exhibit a maximum size at pH 5.0. Rhodamine B (RhB) was chosen as a model compound for drug loading and release studies from P(VCL-co-DMAEMA) on the basis of particles in different phosphate buffer solutions at different temperatures. The temperature/pH-dependent cumulative release and ultrasound-enhanced pulsatile release properties were investigated for RhB-loaded nanogels for long-term and one-shot delivery. The nanogels display efficient delivery for both long-term and one-shot delivery systems. We provide here a proof of concept for the novel use of multiresponsive nanogels having an overall size below 200 nm as a cargo system for hydrophobic drugs and for controlled release mediated by temperature/pH and ultrasound.

Immobilization of water-soluble HRP within poly-N-isopropylacrylamide microgel particles for use in organic media.

In the present work, the immobilization of enzymes within poly-N-isopropylacrylamide (p-NIPAM) microgels using the method of solvent exchange is applied to the enzyme horseradish peroxidase (HRP). When the solvent is changed from water to isopropanol, HRP is embedded within the polymer structure. After the determination of the immobilized amount of enzyme, an enhanced specific activity of the biocatalyst in isopropanol can be observed. Karl Fischer titration is used to determine the amount of water within the microgel particles before and after solvent exchange, leading to the conclusion that an "aqueous cage" remains within the polymer structure. This represents the driving force for the immobilization due to the high affinity of HRP for water. Beside, confocal laser scanning microscopy (CLSM) images show that HRP is located within the microgel network after immobilization. This gives the best conditions for HRP to be protected against chemical and mechanical stress. We were able to transfer a water-soluble enzyme to an organic phase by reaching a high catalytic activity. Hence, the method of solvent exchange displays a general method for immobilizing enzymes within p-NIPAM microgels for use in organic solvents. With this strategy, enzymes that are not soluble in organic solvents such as HRP can be used in such polar organic solvents.

Tunable plasmon coupling in distance-controlled gold nanoparticles.

Plasmons are resonant excitations in metallic films and nanoparticles. For small enough static distances of metal nanoparticles, additional plasmon-coupled modes appear as a collective excitation between the nanoparticles. Here we show, by combining poly(N-isopropylacrylamide) micro- and nanospheres and Au nanoparticles, how to design a system that allows controllably and reversibly switching on and off, and tuning the plasmon-coupled mode.

Immobilization of lipase B within micron-sized poly-N-isopropylacrylamide hydrogel particles by solvent exchange.

The aim of the present work is the use of a water soluble enzyme in an organic solvent, still with a pronounced catalytic activity. Therefore, lipase B from Candida antarctica (CalB) is immobilized within micron-sized thermosensitive p-NIPAM hydrogel particles using a solvent exchange from polar to organic solvents. The absorbed amount of CalB is investigated at different immobilization temperatures. Confocal laser scanning microscopy (CLSM) shows that CalB is homogeneously distributed within the polymer network. An enhanced specific activity of CalB in n-hexane is achieved after immobilization within the p-NIPAM microgels. In order to get information on the supply of the substrate depending on the temperature, the activity is determined at different reaction temperatures. Additionally, the system is stable in the organic solvent, namely n-hexane, and shows a good reusability.

Using hydrogel microparticles to transfer hydrophilic nanoparticles and enzymes to organic media via stepwise solvent exchange.

We present a simple and versatile approach of using hydrogel microparticles to transfer both inorganic hydrophilic nanoparticles (NPs) such as CdTe quantum dots and enzymes such as lipase B from Candida antarctica (CalB) to organic media and eventually encapsulate them in the gel microparticles by consecutive exchange of the water swollen in the hydrogel microparticles with water-miscible organic solvents and water-immiscible solvents. The entrapment of hydrophilic nanoparticles is due to their incompatibility with water-immiscible organic solvents soaked in the gel matrices and in the surrounding environment, so the present approach obviates the need for any chemical modification to the NP surface or to the hydrogel and furthermore does not require any size matching or chemical affinity of the NPs for the hydrogel networks. The solvent exchange process causes little change of the intrinsic properties of hydrophilic nanoparticles; CdTe quantum dots encapsulated in hydrogel microparticles, dispersed in water-immiscible organic solvents, remain strongly fluorescent, and CalB retains high catalytic activity. Of importance is that the hydrophilic nanoparticles encapsulated in the gel microparticles in organic media can be completely recovered in aqueous media via reversed solvent exchange. As a consequence, the present approach should hold immense promise for technical applications, especially in catalysis.

Cooling-Triggered Release from Mesoporous Poly(N-isopropylacrylamide) Microgels at Physiological Conditions.

Poly(N-isopropylacrylamide) (pNIPAM) hydrogels have broad potential applications as drug delivery vehicles because of their thermoresponsive behavior. pNIPAM loading/release performances are directly affected by the gel network structure. Therefore, there is a need with the approaches for accurate design of 3D pNIPAM assemblies with the structure ordered at the nanoscale. This study demonstrates size-selective spontaneous loading of macromolecules (dextrans 10-500 kDa) into pNIPAM microgels by microgel heating from 22 to 35 °C (microgels collapse and trap dextrans) followed by the dextran release upon further cooling down to 22 °C (microgels swell back) . This temperature-mediated behavior is fully reversible. The structure of pNIPAM microgels was tailored via hard templating and cross-linking of the hydrogel using sacrificial mesoporous cores of vaterite CaCO3 microcrystals. In addition, the fabrication of hollow thermoresponsive pNIPAM microshells has been demonstrated, utilizing vaterite microcrystals that had narrower pores. The proposed approach for heating-triggered encapsulation and cooling-triggered release into/from pNIPAM microgels may pave the ways for applications of pNIPAM hydrogels for skin and transdermal cooling-responsive drug delivery in the future.

Stratification of foam films containing polyelectrolytes. Influence of the polymer backbone's rigidity.

We studied the stratification behavior of free-standing foam films which are stabilized by nonionic surfactants and contain polyelectrolytes with different backbone flexibilities, namely sulfonated polyacrylamide (PAMPS), carboxymethyl-chitin (CM-Chitin), Xanthan, and DNA. Stratification is due to a specific arrangement of the polymer chains in the confined environment of the thin films. While stratification is easily observed for films containing PAMPS and CM-Chitin, it is more difficult to observe with Xanthan and DNA. We will discuss this effect in terms of different polymer backbone rigidities, which, in turn, are expected to lead to different time scales for polymer network relaxation.

Reversible activation of diblock copolymer monolayers at the interface by pH modulation, 1: Lateral chain density and conformation.

This study focuses on the design of chemically regulated surfaces that allow for reversible control of the interactions between biological matter (cells and proteins) and planar substrates. As a tunable interlayer, we use a monolayer of a near-monodisperse poly[2-(dimethylamino)ethyl methacrylate-block-methyl methacrylate] (PDMAEMA-PMMA) diblock copolymer. Owing to the relatively large fraction (50%) of the hydrophobic PMMA block, this copolymer forms a stable Langmuir monolayer at the air/water interface. Both in situ and ex situ film balance experiments suggest that the hydrophilic PDMAEMA block adsorbs to the air/water interface in its uncharged state (pH 8.5), but stretches into the subphase in its charged state (pH 5.5). Optimization of the preparation protocols enables us to fabricate stable, homogeneous diblock copolymer films on hydrophobized substrates via Langmuir-Schaefer transfer at well-defined lateral chain densities. Ellipsometry and X-ray reflectivity studies of the transferred films confirm that the film thickness can be systematically regulated by the lateral chain densities. The transferred copolymer films remain stable in water for about a week, suggesting that they are promising materials for the creation of pH-controlled solid substrates for the support of biological matter such as proteins and cells.

Reversible activation of diblock copolymer monolayers at the interface by pH modulation, 2: Membrane interactions at the solid/liquid interface.

A monolayer of the pH-responsive poly[2-(dimethylamino)ethyl methacrylate-block-methyl methacrylate] diblock copolymer [PDMAEMA-PMMA] was transferred from the air/water interface to a silicon substrate for evaluation as a tunable interlayer between biological material and solid substrates. Specular neutron reflectivity experiments revealed that the weak polyelectrolyte PDMAEMA chains at the solid/liquid interface can be reversibly activated by pH modulation. The thickness, scattering length density, and surface roughness of the polymer film can be systematically controlled by pH titration. As a simple model of plasma membranes, a lipid bilayer was deposited onto the polymer film. The membrane-substrate interaction was characterized by neutron reflectivity experiments, demonstrating that the membrane-substrate distance could be reversibly regulated by pH titration. These results confirm the potential of stimuli-responsive polymers for precise control of cell-surface interactions.

Surfactant and metal ion effects on the mechanical properties of alginate hydrogels.

This paper addresses the controlled variation of the mechanical properties of alginate gel beads by changing the alginate concentration or by adding different surfactants or cross-linking cations. Alginate beads containing nonionic Brij 35 or anionic sodium dodecyl sulfate (SDS) surfactants were prepared with two different types of cations (Ca2+, Ba2+) as crosslinkers. Compression measurements were performed to investigate the effect of the surfactant and cation types and their concentrations on the Young's modulus of alginate beads. The Young's modulus was determined by using Hertz theory. For all types of alginate gel beads the Young's modulus showed an increasing value for increasing alginate contents. Addition of the anionic surfactant SDS increases the Young's modulus of the alginate beads while the addition of non-ionic surfactant Brij 35 leads to a decrease in Young's modulus. This opposite behavior is related to the contrary effect of both surfactants on the charge of the alginate beads. When Ba2+ ions were used as crosslinker cation, the Young's modulus of the beads with the surfactant SDS was found to be approximately two times higher than the modulus of beads with the surfactant Brij 35. An ion specific effect was found for the crosslinking ability of divalent cations.

Surface adsorption of oppositely charged C14TAB-PAMPS mixtures at the air/water interface and the impact on foam film stability.

We have studied the oppositely charged polyelectrolyte/surfactant mixture of poly(acrylamidomethylpropanesulfonate) sodium salt (PAMPS) and tetradecyl trimethylammonium bromide (C14TAB) using a combination of neutron reflectivity and ellipsometry measurements. The interfacial composition was determined using three different analysis methods involving the two techniques for the first time. The bulk surfactant concentration was fixed at a modest value while the bulk polyelectrolyte concentration was varied over a wide range. We reveal complex changes in the surface adsorption behavior. Mixtures with low bulk PAMPS concentrations result in the components interacting synergistically in charge neutral layers at the air/water interface. At the bulk composition where PAMPS and C14TAB are mixed in an equimolar charge ratio in the bulk, we observe a dramatic drop in the surfactant surface excess to leave a large excess of polyelectrolyte at the interface, which we infer to have loops in its interfacial structure. Further increase of the bulk PAMPS concentration leads to a more pronounced depletion of material from the surface. Mixtures containing a large excess of PAMPS in the bulk showed enhanced adsorption, which is attributed to the large increase in total ionic strength of the system and screening of the surfactant headgroup charges. The data are compared to our former results on PAMPS/C14TAB mixtures [Kristen et al. J. Phys. Chem. B, 2009, 23, 7986]. A peak in the surface tension is rationalized in terms of the changing surface adsorption and, unlike in more concentrated systems, is unrelated to bulk precipitation. Also, a comparison between the determined interfacial composition with zeta potential and foam film stability data shows that the highest film stability occurs when there is enhanced synergistic adsorption of both components at the interface due to charge screening when the total ionic strength of the system is highest. The additional contribution to the foam stability of the negatively charged polyelectrolyte within the film bulk is also discussed.

Thermoresponsive PDMAEMA Brushes: Effect of Gold Nanoparticle Deposition.

The paper addresses the effect of gold nanoparticle (Au-NP) deposition on the thermoresponsive volume phase transition of the weak polyelectrolyte poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes. PDMAEMA brushes were synthesized via surface-initiated atom transfer radical polymerization (SI-ATRP). The PDMAEMA/Au-NP composite brushes were fabricated by immersing the brush modified wafer in the Au-NP suspension. Atomic force microscopy (AFM), ellipsometry, and scanning electron microscopy (SEM) have been employed to characterize the neat PDMAEMA brushes and PDMAEMA/Au-NP composite brushes. All neat PDMAEMA brushes swelled below the volume phase transition temperature and collapsed with increasing temperature over a broad temperature range independent of the initial brush thickness. Water uptake of the brushes is also independent of initial brush thickness. The adsorption of the charged Au-NPs significantly affects the degree of swelling and the thermoresponsive properties of the brushes. PDMAEMA/Au-NP composite brushes do not exhibit any noticeable phase transition at the experimental temperature range irrespective of the initial brush thickness. The reason for this behavior is attributed to a combination of the following: the decreased conformational entropy of the Au-NP adsorbed polymer chains, the increased hydrophilicity of the system due to the charged Au-NPs, and the ≈13 nm diameter Au-NPs causing steric hindrance. We have also shown that the AFM full-indentation method can be successfully applied to determine the polymer brush thicknesses.

Dynamics of linear poly(N-isopropylacrylamide) in water around the phase transition investigated by dielectric relaxation spectroscopy.

The molecular dynamics of linear poly(N-isopropylacrylamide) (pNIPAM) in aqueous media at temperatures below and above the lower critical solution temperature (LCST) are investigated using broadband dielectric relaxation spectroscopy in a frequency range from 10(-1) to 10(11) Hz. Below the LCST, two relaxation processes are observed in the megahertz and gigahertz region assigned to the reorientation of dipoles of the solvated polymer segments (p-process) and water molecules (w-process), respectively. Both relaxation processes are analyzed using the Havriliak-Negami (HN) function, taking special attention to the w-process. Above the LCST, the dielectric spectra of the pNIPAM solutions resemble that of pure water, showing only the high frequency relaxation process of the water molecules with a more or less Debye-type behavior. The non-Debye behavior of the w-process below the LCST is mainly induced by the interactions between water and pNIPAM chains via hydrogen bonding. The relaxation time and strength of the w-process is studied with dependence on the concentration, temperature, and the polymer chain length (molecular weight). The information obtained is useful for a deeper understanding of the dehydration behavior at the phase transition. The suggestion of dehydration of the pNIPAM chains at the LCST is confirmed by calculating a dehydration number.

Impact of polymer shell on the formation and time evolution of nanoparticle-protein corona.

The study of protein corona formation on nanoparticles (NPs) represents an actual main issue in colloidal, biomedical and toxicological sciences. However, little is known about the influence of polymer shells on the formation and time evolution of protein corona onto functionalized NPs. Therefore, silica-poly(ethylene glycol) core-shell nanohybrids (SNPs@PEG) with different polymer molecular weights (MW) were synthesized and exhaustively characterized. Bovine serum albumin (BSA) at different concentrations (0.1-6 wt%) was used as model protein to study protein corona formation and time evolution. For pristine SNPs and SNPs@PEG (MW=350 g/mol), zeta potential at different incubation times show a dynamical evolution of the nanoparticle-protein corona. Oppositely, for SNPs@PEG with MW≥2000 g/mol a significant suppression of corona formation and time evolution was observed. Furthermore, AFM investigations suggest a different orientation (side-chain or perpendicular) and penetration depth of BSA toward PEGylated surfaces depending on the polymer length which may explain differences in protein corona evolution.