Copolymer Microgels Research Articles

Fluorine-containing pH-responsive core/shell microgel particles: preparation, characterization, and their applications in controlled drug release

A kind of novel fluorine-containing pH-responsive core/shell microgels poly(DMAEMA-co-HFMA)-g-PEG were prepared via surfactant-free emulsion polymerization using water as the solvent. The well-defined chemical structure of the copolymers was characterized by FTIR, 1H-NMR, 19F-NMR, and elemental analysis. The microgel particles were studied by florescence probe technique, dynamic light scattering, and zeta potential measurement; the microgels displayed a significant pH-responsive behavior. Furthermore, the cytotoxicity assay indicated that the copolymer microgels had low toxicity, and 5-FU-loaded microgels offered a certain killing potency against cancer cells. In addition, the drug loading and in vitro drug release demonstrated that 5-FU was successfully incorporated into polymeric microgels, and the drug-loaded microgels showed a marked pH-dependent drug release behavior. This study suggests that the poly(DMAEMA-co-HFMA)-g-PEG microgels play an important role in the release mechanism stimulated by the change in the pH and have potential applications as a controlled drug release carrier.

Injectable Microgel-Hydrogel Composites for Prolonged Small-Molecule Drug Delivery

The design and application of soft nanocomposite injectable hydrogels containing entrapped microgels for small-molecule drug delivery is demonstrated. Copolymer microgels based on N-isopropylacrylamide and acrylic acid were synthesized that exhibited both ionic and hydrophobic affinity for binding to bupivacaine, a cationic local anesthetic used as a model drug. Microgels were subsequently immobilized within an in situ-gelling hydrogel network cross-linked via hydrazide-aldehyde chemistry to generate hydrogel-microgel soft nanocomposites. Drug release could be sustained for up to 60 days from these nanocomposite hydrogels, significantly longer than that achievable using the constituent hydrogel or microgels alone (<1 week). Drug release kinetics could be readily tuned by varying the affinity of the microgel and hydrogel phases for drug-polymer interactions and the network density of the hydrogel phase.

Heterogeneous Morphology of Random Copolymer Microgels as Reflected in Temperature‐Induced Volume Transition and1H High‐Resolution Transverse Relaxation NMR

AbstractThe Flory temperature‐induced volume transition theory for copolymer microgels is generalized for the case of a bimodal heterogeneity of the crosslink density in the microgel particles and applied to PVCL–PNIPAAm and PVCL–PNIPMAAm systems. The most probable morphological parameters are selected from the microscopic and thermodynamic constraints imposed by1H transverse relaxation NMR data and the Flory equation of state in the approximation of a homogeneous morphology. NMR proves the existence of a bimodal heterogeneous morphology of the copolymer microgel particles. Although the systems are different in chemical structure, the heterogeneity parameters obtained from Flory transition theory and NMR transverse relaxation are not essentially different.

Fluorine-containing thermo-sensitive core/shell microgel particles: Preparation, characterization, and their applications in controlled drug release

A novel series of fluorine-containing thermo-sensitive core/shell microgel particels, poly[N-isopropylacrylamide-co-2,2,3,4,4,4-Hexafluorobutyl methacrylate-co-Poly(ethylene glycol) methyl ether methacrylate] [P(NIPAAm-co-HFMA-co-MPEGMA)], were prepared via surfactant free emulsion polymerization. The composition of the copolymer microgels was characterized by FTIR, 1H NMR, and 19F NMR. Subsequently, the thermo-responsive behavior of the microgels was studied by UV–vis spectroscopy, fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. The copolymer microgels exhibited a lower critical solution temperature (LCST) above the normal human physiological temperature. When the temperature was above the LCST, the hydrophobicity of the microgels increased significantly, and the average hydrodynamic diameter decreased greatly. TEM results showed that the copolymer microgels formed loose core–shell spherical particles below the LCST, but above the LCST, the particles became compact and the core–shell structure was not obvious. The drug loading and in vitro release were studied with 5-fluorouracil as a model drug. The result showed that the rate and amount of the drug release became much higher above the LCST. In a word, the study indicated that the fluorine-containing thermo-sensitive copolymer microgels had promising potential applications as a “smart” drug carrier in biomedical field.

Synthesis of cross-linked poly(4-vinylpyridine) and its copolymer microgels using supercritical carbon dioxide: Application in the adsorption of copper(II)

Compared with conventional precipitation polymerization method, cross-linked poly(4-vinylpyridine) (P4VP) and its microgels copolymerized with α-methacrylic acid (MAA) were synthesized through a new route of stabilizer-free polymerization in supercritical fluids. The yellow, dry, fine powders were directly obtained from precipitation polymerization of 4-vinylpyridine in supercritical carbon dioxide (scCO 2) at pressures ranging from 70.0 to 230 bar, using N,N′-methylenebisacrylamide as cross-linker. The effects of the reaction pressure, cross-linker ratio, initiator concentration, and reaction time were investigated. The capacity of this microgel for adsorption of copper(II) was also studied. At higher cross-linker concentrations, a high yield of the cross-linked P4VP microgel was generated in scCO 2, and its particle size was less than 300 nm. Polymerization of cross-linked P4VP in scCO 2 was extremely sensitive to the density of the continuous phase. The adsorption followed the Langmuir isotherm. The adsorption capacities of cross-linked P(4VP- co-MAA) and cross-linked P4VP were 47.2 and 26.9 mg g −1, respectively.

Synthesis and Mass Cytometric Analysis of Lanthanide-Encoded Polyelectrolyte Microgels

This article describes the synthesis and characterization of two series of functional polyelectrolyte copolymer microgels intended for bioassays based upon mass cytometry, a technique that detects metals by inductively coupled plasma mass spectrometry (ICP-MS). The microgels were loaded with Eu(III) ions, which were then converted in situ to EuF(3) nanoparticles (NPs). Both types of microgels are based upon copolymers of N-isopropylacrylamide (NIPAm) and methacrylic acid (MAA), poly(NIPAm/VCL/MAA) (VCL = N-vinylcaprolactam, V series), and poly(NIPAm/MAA/PEGMA) (PEGMA = poly(ethylene glycol)methacrylate, PG series). Very specific conditions (full neutralization of the MAA groups) were required to confine the EuF(3) NPs to the core of the microgels. We used mass cytometry to measure the number and the particle-to-particle variation of Eu ions per microgel. By controlling the amount of EuCl(3) added to the neutralized microgels. we could vary the atomic content of individual microgels from ca. 10(6) to 10(7) Eu atoms, either in the form of Eu(3+) ions or EuF(3) NPs. Leaching profiles of Eu ions from the hybrid microgels were measured by traditional ICP-MS.

Preparation and characterization of poly[acrylamide‐co‐3‐(acryloylamino)propyldodecyldimethylammonium bromide]/polyoxometalate composite microspheres

AbstractSurfmer [3‐(acryloylamino)propyl]dodecyldimethyl ammonium bromide (APDDAB) was synthesized and characterized. On the basis of the reverse emulsion polymerization technique, poly[acrylamide‐co‐3‐(acryloylamino)propyldodecyldimethylammonium bromide] [P(AM‐co‐APDDAB)] copolymer microgels were obtained with the copolymerization of acrylamide and APDDAB. The P(AM‐co‐APDDAB)/polyoxotungstates composite microspheres were prepared with the ion‐exchange reaction of the P(AM‐co‐APDDAB) microgels with phosphotungstic acid (H3PW12O40). The morphologies and components of the composite microspheres were characterized by scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The results indicate that the P(AM‐co‐APDDAB)/PW12O40 composite microspheres all had a core–shell structure. For the composite microspheres, the hydrogel P(AM‐co‐APDDAB) was dominantly located in the core, and the complexes of PW12O403− with APDDAB were mainly located in the surface; these features made the composite microspheres amphiphilic and provided for potential catalysis in a two‐phase reaction. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Cononsolvency of Poly(N,N-diethylacrylamide) (PDEAAM) and Poly(N-isopropylacrylamide) (PNIPAM) Based Microgels in Water/Methanol Mixtures: Copolymer vs Core−Shell Microgel

The cononsolvency effect on the swelling of different stimuli-sensitive microgels was investigated in water/methanol mixtures. Poly(N,N-diethylacrylamide) (PDEAAM) and poly(N-isopropylacrylamide) (PNIPAM) homopolymer microgels, a PDEAAM-core−PNIPAM-shell microgel, and a poly(N,N-diethylacrylamide-co-N-isopropylacrylamide) (P(DEAAM−NIPAM)) microgel have been synthesized. The core−shell and the copolymer microgel have similar compositions; the PDEAAM core of the PDEAAM-core−PNIPAM-shell particle contributes 80% to the total mass, and the copolymer consists of 75% DEAAM and 25% PNIPAM. They were characterized with dynamic light scattering (DLS) and small-angle neutron scattering (SANS). Microgels containing PNIPAM show the cononsolvency effect, and the particle size reaches a minimum at a methanol fraction of xmethanol = 0.2. Moreover, in core−shell microgels, the cononsolvency effect can be limited to one compartment of the particle. A core−shell microgel with a PDEAAM core and PNIPAM shell reveals a sharp ...

Responsive P(NIPAM-co-NtBAM) microgels: Flory–Rehner description of the swelling behaviour

In the present work, a systematic series of poly(N-isopropylacrylamide)(NIPAM) –poly(N-tert-butylacrylamide) (NtBAM) copolymer microgels is prepared by surfactant-free emulsion polymerisation using N,N′-methylenebis(acrylamide) (BIS) as cross-linker. The thermoresponsive behaviour of these colloids was studied in detail applying different scattering techniques. The swelling curves obtained on the basis of photon correlation spectroscopy (PCS) are analysed using the theoretical model of Flory and Rehner. The PCS measurements reveal the narrow particle size distribution of the poly(NIPAM-co-NtBAM) microgels and a decreasing hydrodynamic radius as well as a decreasing volume phase transition temperature (VPTT) with increasing comonomer content. The description of the swelling ratio α as a function of temperature by the Flory–Rehner theory for uncharged homopolymer gels was only partially satisfying and fails for higher comonomer contents. In addition, small angle neutron scattering (SANS) is used to study the internal network structure of these microgels, and the polymer network is characterised in terms of the correlation length ξ. Above the transition temperature, only interfacial scattering from the totally collapsed particles in water can be observed. Due to a certain surface roughness of the copolymer microgels, the SANS profiles beyond the VPTT were fitted using a modified Porod law.

Construction of optical glucose nanobiosensor with high sensitivity and selectivity at physiological pH on the basis of organic–inorganic hybrid microgels

A new class of optical glucose nanobiosensors with high sensitivity and selectivity at physiological pH is described. To construct these glucose nanobiosensors, the fluorescent CdS quantum dots (QDs), serving as the optical code, were incorporated into the glucose-sensitive poly( N-isopropylacrylamide-acrylamide-2-acrylamidomethyl-5-fluorophenylboronic acid) copolymer microgels, via both in situ growth method and “breathing in” method, respectively. The polymeric gel can adapt to surrounding glucose concentrations, and regulate the fluorescence of the embedded QDs, converting biochemical signals into optical signals. The gradual swelling of the gel would lead to the quenching of the fluorescence at the elevated glucose concentrations. The hybrid microgels displayed high selectivity to glucose over the potential primary interferents of lactate and human serum albumin in the physiologically important glucose concentration range. The stability, reversibility, and sensitivity of the organic–inorganic hybrid microgel-based biosensors were also systematically studied. These general properties of our nanobiosensors are well tunable under appropriate tailor on the hybrid microgels, in particular, simply through the change in the crosslinking degree of the microgels. The optical glucose nanobiosensors based on the organic–inorganic hybrid microgels have shown the potential for a third generation fluorescent biosensor.

Thermally Responsive P(M(EO)2MA-co-OEOMA) Copolymers via AGET ATRP in Miniemulsion

Thermally responsive random copolymers of di(ethylene glycol) methyl ether methacrylate (M(EO)2MA) and oligo(ethylene glycol) methyl ether methacrylate (OEOMA) (Mn ∼ 300 or 475) with varied compositions were successfully synthesized via activators generated by electron transfer for atom transfer radical polymerization (AGET ATRP) in miniemulsion at 65 °C. The copolymerizations were controlled, generating well-defined copolymers with relatively narrow molecular weight distribution (Mw/Mn ∼ 1.3−1.5). Because of the relatively high reaction temperature (65 °C), OEOMA was confined into oil phase, although OEOMA was miscible with water in all proportions at room temperature. The compositional study proved that the composition of the copolymers reflected the comonomer feed ratio. The cloud point of the resulting copolymer increased proportionally with the OEOMA molar content. Microgels of P(M(EO)2MA-co-OEOMA) were also prepared by addition of ethylene glycol dimethacrylate (EGDMA) cross-linker. Similar to their linear analogues, the phase transition temperature of the copolymer microgels can be tuned by changing OEOMA content in the microgels.

UCST Responsive Microgels of Poly(acrylamide−acrylic acid) Copolymers: Structure and Viscoelastic Properties

Positive thermosensitive microgels were obtained via the inverse emulsion polymerization method with controlled feeding system. Random acrylamide and acrylic acid copolymer microgels with different compositions were synthesized and characterized. Dynamic light scattering was used to determine the hydrodynamic diameter and swelling behavior. The morphology, distribution, and size were determined by scanning electron microscopy (SEM). Cross-linker and acrylic acid concentration of the copolymer affected collapse temperature of the swelling behavior. An oscillatory rheometer was used to study the viscoelastic properties. The viscoelastic modulus G′, and G′′, of the microgel nanoparticle dispersions suggested a solidlike behavior. A scaling theory was applied to describe the structure of microgel dispersion, and the fractal dimension of the aggregates was obtained.

Optically pH and H2O2 Dual Responsive Composite Colloids through the Directed Assembly of Organic Dyes on Responsive Microgels

A novel type of smart composite materials based on the directed assembly of organic dyes on a responsive microgel template was prepared and investigated. We have chosen Calcon, a monoazo dye, as model organic dye molecules and the copolymer microgel of poly(N-isopropylacrylamide-acrylic acid-acrylamide) [p(NIPAM-AA-AAm)] as template with the pAA segments designed for inducing pH-sensitivity and the pAAm segments designed for directing the highly ordered assembly of dye molecules. Transmission electron microscopy, X-ray scattering, and light scattering were used to study the dye assembling structures and the pH-induced volume phase transitions of the composite microgels. The UV−vis absorption and photoluminescence properties of the composite microgels were respectively investigated at different pH values and H2O2 concentrations. The pH-induced shrinkage of the template microgels not only results in a systematic shift in the wavelength of bands, but also significantly increases the absorption and emission i...

Amphoteric Core−Shell Microgels: Contraphilic Two-Compartment Colloidal Particles

pH-responsive amphoteric core-shell microgel particles were synthesized by emulsion copolymerization of the appropriate functional monomers with ethylene glycol dimethacrylate as the cross-linker. 2-(Diethylamino)ethyl methacrylate (DEA) was used as the ionizable basic monomer, and tert-butyl methacrylate served as the hydrophobic monomer precursor, which gave the methacrylic acid (MAA) moieties following acid hydrolysis of the ester groups. The core of the polyampholyte microgels comprised a cross-linked poly(2-(diethylamino)ethyl methacrylate) (PDEA) or poly(methacrylic acid) (PMAA) network surrounded by a cross-linked PMAA or PDEA shell, respectively. A polyampholyte random copolymer microgel with the DEA and MAA units randomly distributed within the gel phase was also prepared. Scanning electron microscopy studies showed spherical particles of a narrow size distribution, and transmission electron microscopy verified the core-shell topology of the particles. Potentiometric titration curves revealed two plateau regions for the polyampholyte core-shell microgels attributed to the independent ionization process of the core and the shell of the particles, in contrast to the random copolymer microgel particles that exhibited a single plateau region as a result of the simultaneous protonation/deprotonation process of the basic and acidic moieties of the microgels. The core and the shell of the particles were found to swell independently upon ionization of the DEA or MAA moieties at low or high pH, respectively, whereas collapsed latex particles were obtained in the intermediate pH range when both the core and the shell of the particles were neutral, in agreement with the potentiometric titration data. These core-shell microgels comprise novel two-compartment nanostructures that exhibit contraphilic properties in the core and the shell of the particles in response to a single external stimulus.

Novel pH‐ and Temperature‐Responsive Methacrylamide Microgels

AbstractA novel transition temperature in MeAM copolymer microgels is reported. Despite the fact that MeAM homopolymers do not show thermosensitive properties, a specific synthetic strategy leads to a thermo‐responsive swelling behavior that could be potentially useful in medical and/or industrial applications. The pH and temperature‐dependent swelling response of microgels of MeAM copolymerized with 2‐aminomethylpyridine and ethylenediamine is reported. The changes in particle sizes, which depend on the nature of the surrounding environment, are recorded by QELS. The relation between copolymer structure and its novel behavior is analyzed by several techniques (1H NMR, TGA).magnified image

Functionalised Microgels for Acrylic Coatings

AbstractSummary: Aqueous acrylic dispersions of hydroxy‐functionalised copolymer microgel particles crosslinked with allyl methacrylate were synthesized by emulsion polymerization. The microgels were investigated as reactive polymer fillers in mixtures with a water‐borne film‐forming dispersion. Properties of coatings cast from mixtures of aqueous dispersion of hard microgel particles and film‐forming water‐borne dispersion were investigated. The swelling behaviour of microgels in selected solvents (aliphatic ketones) as a function of microgel composition is discussed as well. It was found that the swelling ability of microgels decreased with growing degree of crosslinking. Microgels comprising copolymerised butyl methacrylate swelled less in aliphatic ketones than microgels without this comonomer. This work was focused mainly on the influence of microgels incorporated in the commercial solvent‐borne acrylic binders on the properties of coatings. It was shown that the application of microgels that were redispersed in acetone did not affect the surface appearance and transparency of coatings. Moreover, the presence of microgel network precursors accelerated film curing at ambient temperature and improved the final hardness of coatings.

Tunable Photoluminescence of Ag Nanocrystals in Multiple-Sensitive Hybrid Microgels

We report here fluorescent pH-sensitive hybrid materials based on the in situ immobilization of Ag and Ag/Au bimetallic nanoparticles (NPs) in the interior of multiple sensitive copolymer microgels of poly(N-isopropylacrylamide-co-acrylic acid-co-acrylamide) with polyacrylamide fragments serving as stabilizing ligands. Temperatures corresponding to the swollen, partially swollen, and nearly collapsed states of the template microgels were respectively applied for loading and in situ chemical reduction of Ag+ ions to control the size and size distribution of the Ag NPs in the microgels. Au nanoclusters were stably grown on the surface of Ag NPs through a galvanic replacement reaction between Ag and AuCl4−. The pH-sensitive optical properties of hybrid microgels embedded with either Ag NPs or Ag/Au bimetallic NPs were systematically investigated. The gradual protonization of poly(acrylic acid) fragments shrank the microgels, resulting in an enhancement of photoluminescence (PL) intensity and a blue shift of ...

Temperature Sensitive Copolymer Microgels with Nanophase Separated Structure

Small-angle neutron scattering data from a thermosensitive copolymer microgel consisting of N-isopropylacrylamide (PNIPAM) and N-isopropylmethacrylamide (PNIPMAM regions) were analyzed using a new form factor model. The neutron scattering data display an exceptional shape of the scattering curve at the transition temperature of the microgel indicating an additional characteristic length scale inside the microgel. A new form factor model with a nanophase separated internal morphology was derived which describes the experimental scattering very well. At the transition temperature of the copolymer, which is in between the transition temperatures of the two components, the copolymer microgel particles consist of collapsed PNIPAM domains and swollen PNIPMAM regions. The results demonstrate that a one-pot synthesis can lead to a highly sophisticated material with phase separated domains on a microscopic length scale.

Multiresponsive Hybrid Colloids Based on Gold Nanorods and Poly(NIPAM-co-allylacetic acid) Microgels: Temperature- and pH-Tunable Plasmon Resonance

This work describes the control and manipulation of the optical properties of multiresponsive organic/inorganic hybrid colloids, which consist of thermo-responsive poly-(NIPAM-co-allylacetic acid) microgel cores and gold nanorods assembled on their surface. These composites are multifunctional, in the sense that they combine the interesting optical properties of the rod-shaped gold particles--exhibiting two well-differentiated plasmon modes--with the sensitivity of the copolymer microgel toward external stimuli, such as temperature or solution pH. It is shown that the collapse of the microgel core, induced by changes in either temperature or pH, enhances the electronic interactions between the gold nanorods on the gel surface, as a result of the subsequent increase of the packing density arising from the surface decrease of the collapsed microgel. Above a certain nanorod density, such interactions lead to remarkable red-shifts of the longitudinal plasmon resonance.

Semi-quantitative analysis of the monomer composition in co-polymer microgels using solid state Raman and NMR spectroscopy

A series of colloidal microgels have been prepared by surfactant-free emulsion polymerisation (SFEP) based on the N-isopropylacrylamide (NIPAM) monomer. 4-Vinylpyridine (4-VP) and butylacrylate (BuA) have been used as co-monomers. Co-polymer poly(NIPAM/4-VP) and poly(NIPAM/BuA) have been prepared with various monomer ratios, ranging from pure poly(NIPAM) to pure poly(BuA)/poly(4-VP). Freeze-dried samples of the microgels have been analysed by solid state (ss) Raman and NMR (Nuclear Magnetic Resonance) spectroscopy to investigate the monomer composition in the co-polymer microgels. Spectral data have been analysed graphically and also statistically. Spectroscopic measurements have shown that co-polymerization has occurred. The graphical and statistical analysis of the spectroscopic data for both co-polymer microgels, enables the semi-quantitative measurement of the percentage incorporation of co-monomers (4-VP/BuA) in the co-polymer microgels. A good correlation exists between the Raman and NMR results, however, Raman spectroscopy is much less time consuming (Raman spectral acquisition time is less than 10 minutes) and the measurements are easy to make and very small quantities (less than 1 mg) of the sample are required. This compares with the experimental measurements of approximately 72 hours and 100-200 mg of sample that are required for the NMR experiments.