Charged Microgels Research Articles

Preparation and Characterization of Oxidized Starch Polymer Microgels for Encapsulation and Controlled Release of Functional Ingredients

A novel biocompatible and biodegradable microgel system has been developed for controlled uptake and release of especially proteins. It contains TEMPO-oxidized potato starch polymers, which are chemically cross-linked by sodium trimetaphosphate (STMP). Physical chemical properties have been determined for microgels of different weight ratios of cross-linker to polymer (0.10, 0.15, 0.20, 0.30, and 0.40) and degrees of oxidation (30, 50, 70, and 100%). The charge density of the microgels as determined by proton titration is found to be in good agreement with the expected degree of oxidation (DO). The electrophoretic mobility of the microgel particles is used as a qualitative indicator of the pore size and scales with microgel swelling capacity as expected. The swelling capacity increases with increasing pH and decreasing salt concentration. Preliminary data for the uptake of the globular protein lysozyme by the microgels show it increases with increasing DO and decreasing cross-linker to polymer ratio. Highly charged microgels with intermediate cross-linker to polymer ratios (0.15 and 0.2) are found to be optimal for encapsulating lysozyme.

Temperature-Sensitive Poly(vinyl alcohol)/Poly(methacrylate-co-N-isopropyl acrylamide) Microgels for Doxorubicin Delivery

Microgels based on poly(vinyl alcohol), PVA, grafted with methacrylate side chains, MA, incorporating N-isopropylacrylamide, NiPAAm, monomer, were prepared by water-in-water emulsion polymerization method. These systems exhibit a spherical shape and a volume-phase transition, that is, shrinking, below physiological temperature. The behavior of these microgels were studied with respect to their average size and size distribution, swelling, and release properties. It was observed that the stirring speed is a key parameter for controlling the amount of incorporated NiPAAm, the particle size and the sharpness of the volume-phase transition. The volume-phase transition temperature, VPPT, of the microgels was evaluated around 38 and 34 degrees C for microgels with a NiPAAm/methacrylate molar ratio of 0.8 and 2.4, respectively. Water uptake increased with the amount of NiPAAm monomer present in the polymer network. In vitro biocompatibility of microgels was assessed with respect to NIH3T3 mouse fibroblasts. O-Succinoylated microgels were loaded with doxorubicin by exploiting the favorable electrostatic interaction between negatively charged microgel surface and positively charged doxorubicin. The drug release was influenced by the microgels surface/volume ratio. At physiological temperatures, above the VPTT exhibited by these systems, the release was enhanced by the specific area increase. This study provides the background for the design of an injectable device suitable for the controlled delivery of doxorubicin based on the volume-phase transition of microgels.

Effects of Cations on the Sorting of Oppositely Charged Microgels

Two kinds of thermally sensitive oppositely charged polymeric microgels, poly(N-isopropylacrylamide-co-sodium acrylate) (NIPAM-co-SA) and poly(N-isopropylacrylamide-co-vinylbenzyl trimethylammonium chloride) (NIPAM-co-VT), have been prepared by dispersion polymerization. Their temperature-induced aggregation was studied by use of laser light scattering. In the absence of a salt, NIPAM-co-SA and NIPAM-co-VT microgels in the mixture do not aggregate but shrink upon the heating. The addition of monovalent cations does not affect the aggregation. In the presence of divalent metal ions, the heating leads to the association of NIPAM-co-SA microgels via the complexation of metal ions and carboxyl groups on the microgel surface when the temperature approaches their lower critical solution temperature (LCST approximately 32 degrees C). Further heating over the LCST results in the adsorption of NIPAM-co-VT microgels on the NIPAM-co-SA aggregate via the electrostatic attraction so that a core-shell structure with a NIPAM-co-SA core and a NIPAM-co-VT shell forms, resembling the biological cell-sorting.

Intergel interpolyelectrolyte reaction and synthesis of hybdrid composites based on charged microgels and inorganic nanocrystals

We have studied the interaction between oppositely charged microparticles of polyelectrolyte hydrogels whose low-molecular-mass counterions form insoluble compounds. The intergel polyelectrolyte reaction of such polymers leads to formation of a crystalline compound in the microgel mixture phase. The asprepared samples are composites containing, along with unreacted microgel regions, the interpolyelectrolyte complex comprising the intercrystalline low-molecular-mass compound. It has been shown that both unreacted microgel regions and insoluble compound incorporated into the intergel complex can be involved in chemical modification.

Hierarchically aligned porous scaffold by ice-segregation-induced self-assembly and thermally triggered electrostatic self-assembly of oppositely charged thermosensitive microgels

We present a new method for the fabrication of a 3-dimensional hierarchical aligned porous scaffold by a combined ice-segregation-induced self-assembly and thermally triggered electrostatic self-assembly method. The oppositely charged thermosensitive microgels were used as the building blocks of the scaffold. The porous structure can be controlled by adjusting both the directional freezing conditions and microgel components. The scaffold thus prepared may survive in a physiological environment (37 °C in water) and has great potential in biomedical applications such as tissue engineering.

Interactions between Homopolypeptides and Lightly Cross-Linked Microgels

The relative importance of electrostatic and nonelectrostatic interactions in peptide-microgel systems was evaluated by micromanipulator-assisted light microscopy, confocal microscopy, and circular dichroism. For this purpose, the interaction of various homopolypeptides with lightly cross-linked polyelectrolyte gel particles ( approximately 70 microm in diameter) was studied with focus on peptide-induced microgel deswelling and its relation to peptide distribution within the microgel particles. Negatively charged poly-l-glutamic acid (pGlu) and poly-l-aspartic acid (pAsp), as well as uncharged poly-l-proline (pPro) and poly-l-threonine (pThr), were found to not bind to negatively charged poly(acrylic acid) microgels under the conditions investigated, but were instead depleted from the microgel particles. Positively charged poly-l-arginine (pArg), poly-l-histidine (pHis), and poly-l-lysine (pLys), on the other hand, interacted strongly with the oppositely charged microgel particles and caused significant deswelling of these. In parallel, cationic acrylamidopropyltriethylammoniumchloride (APTAC) microgels bound negatively charged polypeptides to a much higher extent than positively charged and uncharged ones. These findings suggest that electrostatic interactions dominate peptide binding and resulting microgel deswelling in these systems. Nevertheless, although the amount of cationic peptide bound to the anionic microgel particles was similar for cationic pLys, pArg, and pHis, peptide-induced gel deswelling differed significantly, as did the change in peptide conformation after microgel binding and the peptide distribution within the microgels. These effects, as well as pH dependent binding and release of titrable pHis, are discussed in terms of the effects of the charge density of, and structural differences between, the cationic homopolypeptides on the interaction with the oppositely charged microgel particles.

Structural Ordering and phase Behavior of Charged Microgels

Structural Ordering and phase Behavior of Charged Microgels

Structural Ordering and Phase Behavior of Charged Microgels

Recent theoretical phase diagrams for loosely cross-linked ionic microgels with a low monomer volume fraction (Gottwald; et al. Phys. Rev. Lett. 2004, 92 , 068301 ) have predicted a re-entrant order-disorder transition (i.e., fluid-FCC-BCC-fluid) as a function of concentration and so far there has been no experimental verifications of these theoretical predictions. Here, we present experimental results on phase behavior of loosely cross-linked charged poly(N-isopropylacrylamide co acrylic acid) (PNIPAm-co-AAc) microgesls with a low monomer volume fraction (approximately 0.003) for a wide range of concentrations (0.02-0.6 wt %) using static and dynamic light scattering methods. These microgel dispersions exhibit a short-range liquid order at low concentration (<0.03 wt %), a FCC crystalline order at intermediate concentrations (0.03- 0.3 wt %). In addition, we suggested a possible coexistence of BCC and FCC phases at higher concentration crystalline suspension (approximately 0.34 wt %). These results clearly demonstrate the experimental verification of above theoretical prediction below the overlap concentration and also reveal that the interaction potential between the microgel particles is of screened Coulomb repulsive type within these concentration ranges. At further higher concentration (approximately 0.57 wt %), we once again observed a disordered state and this disordered state from dynamic light scattering was confirmed to be a glass. These initial results are discussed in the light of previously reported results on the phase behavior of ionic microgel colloidal dispersions.

Defined Complexes of Negatively Charged Multisensitive Poly(N-isopropylacrylamide-co-methacrylic acid) Microgels and Poly(diallydimethylammonium chloride)

The influence of poly(diallyldimethylammonium chloride) (PDADMAC) on pH- and temperature-sensitive negatively charged microgels was investigated with regards to different ratios between positive charges having their origin in PDADMAC and negative charges resulting from copolymerization of N-isopropylacrylamide (NiPAM) with methaacrylic acid (MAA). The concentration of the PDADMAC solution (regarding to monomeric units) was determined by argentometric and polyelectrolyte titration, the amount of MAA in the microgel was characterized with conductometric titration. The composition of the complexes between microgel and PDADMAC was available by centrifugation of the mixture and comparing the PDADMAC concentration in the supernatant with the initial concentration. Different from many other systems, we observed no flocculation at any microgel and PDADMAC ratio, but stable complexes were obtained. Because of the softness of a microgel in contrast to rigid particles, the microgel properties are strongly altered by the polyelectrolyte. Consequently, size, ζ-potential as well as the pH and temperature sensitivity of the microgel−polyelectrolyte complexes can be influenced by the adsorbed polyelectrolyte. Thus, polyelectrolyte adsorption allows tailoring the behavior of “smart” environmentally sensitive microgels.

Bimodal Swelling Responses in Microgel Thin Films

A series of studies on microgel thin films is described, wherein quartz crystal microgravimetry (QCM), surface plasmon resonance (SPR), and atomic force microscopy (AFM) have been used to probe the properties of microstructured polymer thin films as a function of film architecture and solution pH. Thin films composed of pNIPAm-co-AAc microgels were constructed by using spin-coating layer-by-layer (scLbL) assembly with poly(allylamine hydrochloride) (PAH) as a polycationic "glue". Our findings suggest that the interaction between the negatively charged microgels and the positively charged PAH has a significant impact on the pH responsivity of the film. These effects are observable in both the optical and mechanical behaviors of the films. The most significant changes in behavior are observed when the motional resistance of a quartz oscillator is monitored via QCM experiments. Slight changes to the film architecture and alternating the pH of the environment significantly changes the QCM and SPR responses, suggesting a pH-dependent swelling that is dependent on both particle swelling and polyelectrolyte de-complexation. Together, these studies allow for a deeper understanding of the morphological changes that take place in environmentally responsive microgel-based thin films.

Interpolyelectrolyte reaction between the particles of oppositely charged microgels

Processes that take place in oppositely charged microgel particles were studied. It was shown that water-swollen microgel particles about 100 μm in size were capable of interacting in dilute and concentrated dispersions to produce continuous dispersed systems. This interaction is accompanied by the release of water and low-molecular-mass counterions of network polyelectrolytes. Their liberation is due to the interpolyelectrolyte reaction between peripheral regions of unlike charged microgel particles in the particle contact zone.

Visualizing the Interaction between Poly-l-lysine and Poly(acrylic acid) Microgels Using Microscopy Techniques: Effect of Electrostatics and Peptide Size

The interaction between lightly cross-linked poly(acrylic acid) (pAA) microgels (50-150 microm in diameter) and poly-L-lysine (pLys) was studied as a function of pH, ionic strength, peptide size, and concentration. The swelling response and distribution of polypeptides within microgel particles was monitored by micromanipulator-assisted light microscopy and confocal laser scanning microscopy, while binding isotherms of pLys in the microgels were determined spectrophotometrically. Conformational changes of pLys were investigated by circular dichroism. The molecular weight of pLys was found to influence the degree of peptide-induced microgel deswelling, largely due to limitation of peptides larger than the effective network mesh size to penetrate the entire gel. Large peptides were concentrated within a surface layer of the gel particles, and at low ionic strength this dense surface layer was shown to act as a largely steric barrier for further penetration of compounds into the gel core. Small peptides, however, distributed evenly throughout the microgel particles and were able to create large microgel volume reductions. The deswelling of microgels increased with decreasing pH, while the uptake of pLys was significantly reduced at low pH. The effect of ionic strength on the interactions of pLys and oppositely charged pAA microgels was moderate and only pronounced for deswelling of gels at high pH. A significant increase in the alpha-helix content of pLys interacting with the oppositely charged microgels was observed for high molecular weight peptides, and the extent of alpha-helix formation was as expected more pronounced at high pH, i.e., at high charge density of the microgels but reduced charge density of the peptides.

Self-Exploding Lipid-Coated Microgels

Self-exploding microparticles show potential for advanced delivery of certain therapeutics. This study evaluates (1) whether degrading biodegradable dextran hydroxyethyl methacrylate (dex-HEMA) microgels can be coated by a lipid membrane and (2) whether the surrounding membrane can be ruptured by the increasing swelling pressure of the degrading microgel. We found that adsorption of charged liposomes to oppositely charged dex-HEMA microgels provides efficient coating of the microgels, whereby microparticles with a "core-shell" structure were clearly obtained. Especially, we could confirm experimentally that the swelling pressure increase of degrading dex-HEMA microgels can destroy the lipid membrane surrounding the microgels.

Photoresponsive Surfactants in Microgel Dispersions

Microgel particles are cross-linked polymer particles. When dispersed in a good solvent for the polymer concerned, they are able to respond to a range of external stimuli by changing volume. Hence, microgel particles are suited to numerous applications (for example, controlled uptake and release) in the pharmaceutical, coatings, and water treatment industries. In this work, pH-sensitive, 0.5 wt % cross-linked poly(2-vinylpyridine) (PVP) microgel particles have been prepared and characterized. When the dispersion pH is decreased below 4.5, the pyridine groups become protonated and the microgel network becomes positively charged, causing the particles to expand. To investigate the possibility of using light as a trigger for effecting volume changes, the interaction of these microgel particles with a photodegradable anionic surfactant, 4-hexylphenylazosulfonate (C(6)PAS), has been investigated using dynamic light scattering and electrophoretic mobility measurements. The electrostatic attraction between the positively charged microgel network (at solution pH 3) and the negatively charged headgroups on the surfactant molecules caused a dramatic decrease in particle volume, and charge-reversal of the particles occurred with increasing surfactant concentration. The UV irradiation of phenylazosulfonate surfactants destroys the anionic headgroup of the molecules, and the microgel particles re-swell. The irradiation of PVP dispersions in the presence of C(6)PAS, along with mixed surfactant systems of sodium dodecyl sulfate plus C(6)PAS, has been investigated.

Microstructure and rheological properties of pH-responsive core–shell particles

The microstructure and rheological properties of core–shell pH-responsive microgels consisting of poly(methyl methacrylate) (PMMA) particles grafted with a soft layer of methacrylic acid–ethyl acrylate (MAA–EA) cross-linked with di-allyl phthalate (DAP) were examined using dynamic light scattering and rheological techniques. The validity and limitation of the semi-empirical approach to model charged soft microgel particles developed by our group were tested on this core–shell system. The viscosity data for three different core–shell particles showed excellent agreement with the modified Krieger–Dougherty (K–D) model. Good agreement was also observed when our semi-empirical approach was compared against a theoretical model, which confirmed the validity of the semi-empirical approach to model charged soft particles. In addition, we confirmed that the new scaling law which relates the swelling ratio Q of microgels as a function of neutralization degree, α, average number of monomers between two cross-links, N x , molar fraction of acidic units, y and concentration of mobile counter-ions, C K + and C Na + , represented as ( N x / c 0 ) ( C K + + C Na + ) Q + Q 2 / 3 is proportional to yN x α. All the core–shell data at varying ionic strength and mobile counter-ions concentrations fall onto a master curve.

Predicting equilibrium structures in freezing processes

We propose genetic algorithms as a new tool that is able to predict all possible solid candidate structures into which a simple fluid can freeze. In contrast to the conventional approach where the equilibrium structures of the solid phases are chosen from a preselected set of candidates, genetic algorithms perform a parameter-free, unbiased, and unrestricted search in the entire search space, i.e., among all possible candidate structures. We apply the algorithm to recalculate the zero-temperature phase diagrams of neutral star polymers and of charged microgels over a large density range. The power of genetic algorithms and their advantages over conventional approaches is demonstrated by the fact that new and unexpected equilibrium structures for the solid phases are discovered. Improvements of the algorithm that lead to a more rapid convergence are proposed and the role of various parameters of the method is critically assessed.

A semi-empirical approach for modeling charged soft microgel particles

We describe a unified semi-empirical approach for predicting the viscosity of dilute and concentrated hard and soft sphere systems. A variable specific volume, k was introduced to convert the mass concentration to effective volume fraction. With increasing particle concentration, the concentration of free counter-ions in the solution can be large enough to induce an osmotic de-swelling of soft particles, resulting in the particle shrinkage. The viscosity data for four different microgel systems at different neutralization degree showed excellent agreement with the modified Krieger–Dougherty model.

The use of poly (N-isopropylacrylamide) microgels as a multi-functional processing aid for aqueous alumina suspensions

Two temperature sensitive microgels of poly (N-isopropylacrylamide) were prepared, one anionic in nature and the other cationic. The microgels were concentrated by centrifugation and the rheological properties of the microgels measured as a function of temperature. The anionic microgel showed a transition from an elastic gel like structure to a liquid like structure at 32°C, whilst the cationic microgel demonstrated the same transition, but at a slightly higher temperature of 34°C. Both systems were completely reversible. A sub micron sized alumina powder was then mixed into the microgels using an anionic dispersant, (Darvan 821A ) to stabilise the powder. The powder was added until the system was just reversible. The aim was to see which microgel behaved as the best processing aid for the alumina particles, in terms of dispersion, gelation and adhesion after drying. The resulting mixtures were freeze dried, sintered and investigated by electron microscopy. The best microgel / alumina system was the one with similarly charged particles, i.e. the anionic microgel, whereas the system containing the oppositely charged cationic microgel particles flocculated, as would be expected from simple electrostatic theory. The presence of the inorganic particles caused the sharp transition from elastic gel to viscous fluid to broaden and the systems to behave viscoelastically over the whole temperature range. Sintered products made from the two systems were remarkably different. With the cationic microgel the resulting structures crumbled, but with the anionic microgel robust structures were obtained. Hence it is feasible to use similarly charged microgels as processing aids for ceramics as long as both particles are not oppositely charged.

Influence of charge density on the swelling of colloidal poly( N-isopropylacrylamide-co-acrylic acid) microgels

The volume phase transition of colloidal poly( N-isopropylacrylamide-co-acrylic acid) microgels depends in a complex way on the effective charge density within the polymer network. A series of monodisperse PNIPAM/AAc microgels with different content of acrylic acid were synthesized by surfactant-free emulsion polymerization employing sonication instead of a conventional stirring technique. Subsequently, the colloids were characterized by dynamic light scattering and electron microscopy. Potentiometric titrations provided the amount of carboxyl groups incorporated into the copolymer. The effective charge density was systematically controlled by the content of acrylic acid monomers, the pH value of the suspension, and the salt concentration. The hydrodynamic dimensions of the microgels have been measured by dynamic light scattering. The swelling/deswelling behavior is determined by the delicate balance between hydrophobic attraction of NIPAM and the repulsive electrostatic interactions of the carboxylate group of the acrylic acid moieties. Compared to their macroscopic counterparts the charged microgel particles show a significantly different swelling/deswelling behavior. This manifests in the occurrence of a two-step volume phase-transition process with increasing acrylic acid content. Hydrogen bonding has to be considered to understand this two step volume phase transition uniquely observed for colloidal microgels. Another interesting phenomenon presented here is the reversible formation of well-defined aggregates at low pH and under high salt conditions.

Motion of microgel particles under an external electric field

The influence of the swelling of charged microgel particles on their motion under an external electric field has been studied. The selected experimental observable was the electrophoretic mobility of the particles, which was measured as a function of the pH since its value controls the electrical charge of the particles. The mobility-pH curve presents a maximum and a minimum as a consequence of the competition between charge-density and friction coefficient variations during swelling. Ohshima's theory for polyelectrolyte-coated particles was employed, describing qualitatively the experimental results. Quantitative discrepancies suggest that charge renormalization should be considered.