Multi‐responsive microgel of a water‐soluble monomer via emulsion polymerization

Microgel of a water‐soluble monomer [2‐(N‐morpholino)ethyl methacrylate (MEMA)] was successfully prepared in aqueous media via emulsion polymerization by using a novel water‐soluble block copolymer as stabilizer. Characterization studies confirmed monodisperse spherical morphologies of microgels with a diameter of 280 nm at neutral pH. These microgels exhibited multi‐responsive behavior by responding solution pH, temperature, ionic strength, type of dispersing media, and magnetic particles. It swells well at low pH (<6.0) and at low temperature, but shrinks above pH 6.0, or even more shrinks with salt addition at neutral and basic conditions. In addition, the hydrodynamic diameter of PMEMA microgel was decreased gradually at basic and neutral pH when solution temperature was increased up to the lower critical solution temperature of PMEMA (LCST, 35°C), but microgel diameter did not change much above LCST. Multi‐responsive behavior of PMEMA microgel was investigated by using dynamic light scattering, UV‐Vis spectrophotometer and zeta potentiometer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42072.     

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.     

温敏性微凝胶对蛋白质和酶的吸附性能

用微乳液聚合方法以N-异丙基丙烯酰胺为单体合成了温敏性微凝胶聚N-异丙基丙烯酰胺(PNIPAM),研究了其对两种蛋白质和两种酶的吸附性能,测定了吸附等温线和温度对吸附量的影响。结果表明,微凝胶在低临界溶解温度(LCST)附近吸附蛋白质和酶的量有一突跃,例如在LCST前后,1 g纳米颗粒吸附的酪蛋白的质量分别为225 mg和415 mg;吸附的枯草杆菌蛋白酶的质量分别为12 000U/mg和27 500 U/mg。蛋白质和酶是通过物理吸附作用结合到PNIPAM微凝胶上,可以用调节温度的方法,来控制温敏微凝胶对蛋白质和酶的吸附与脱附。     

Microstructure and rheological properties of thermo-responsive poly(N-isopropylacrylamide) microgels

The microstructure and rheological properties of thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) microgels cross-linked with methylenebis-acrylamide (BA) were examined by dynamic light scattering and rheological techniques. As the temperature was increased from 10 to 50 °C, the particles diameter decreased by approximately two times near the volume phase transition temperature, T_v of between 30 and 35 °C. The addition of salt to the microgel dispersion provides competition for the water molecules hydrating the PNIPAM chains thus weakening the PNIPAM-H₂O hydrogen bonds and the microgel progressively deswelled. The validity and limitation of the semi-empirical approach to model charged soft microgel particles developed previously were tested on this thermo-responsive system. A variable specific volume, k was introduced to convert the mass concentration to effective volume fraction. With increasing concentration, inter-particle repulsive force was enhanced, which overcame the osmotic force inside the soft particle, resulting in the expulsion of solvent from the swollen particles, and the particle shrank. The viscosity data for PNIPAM microgels at varying solution temperatures and ionic strength showed excellent agreement with the modified Krieger-Dougherty (K-D) model.     

Thermoresponsive surfaces by spin-coating of PNIPAM-co-PAA microgels: A combined AFM and ellipsometry study

Thermosensitive coatings are fabricated by spin-coating of microgels consisting of the cross-linked copolymer poly(N-isopropyl acrylamide-co-acrylic acid) (P(NIPAM-co-AA)) on silicon wafers. The microgels were synthesized with two different cross-linker molar ratios and the thin films were prepared at pH 2. At this pH the particles are negatively charged only due to the starter used for the polymerization. Scanning force microscopic (AFM) images indicate a dense packing of the particles and a strong flattening in the adsorbed state. This effect is stronger for microgels containing less cross-linker. Coatings consisting of these microgel particles show a reversible thermoresponsive swelling/shrinking in the region of the lower critical solution temperature (LCST) of NIPAM. For the ellipsometric study of this process a standard setup was modified in order to allow temperature dependent measurements of the optical thickness in a liquid cell. The temperature induced transition is sharper in the case of microgels with lower amount of cross-linker and smears out with increasing amount of cross-linker. No significant desorption of the particles occurs at pH 2, which was shown by AFM of the dried films before and after the ellipsometric measurements. In the dry state the average thickness of the prepared films is approximately 30 nm and a thickness of about 400 nm is reached in the swollen state.     

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, CK⁺ and C⁺Na, represented as (Nx/c₀)(CK⁺+C⁺Na)Q+Q2/3 is proportional to yN_xα. All the core-shell data at varying ionic strength and mobile counter-ions concentrations fall onto a master curve.     

Fabrication and characterization of microgel-impregnated, thermosensitive PNIPAAm hydrogels

Poly(N-isopropylacrylamide)/poly(ethylene glycol) diacrylate (PNIPAAm/PEG-DA) microgels were used as an additive during the polymerization and/or crosslinking of PNIPAAm hydrogels to improve their thermosensitive properties. The influence of this additive on the property of resulting PNIPAAm hydrogels was investigated and characterized. The interior morphology by scanning electron microscopy (SEM) revealed that microgel impregnated PNIPAAm hydrogels have tighter and constrained porous network structures, although large cavities of 30-40 μm in diameter, occupied by the microgels were sporadically distributed in this constrained network. Differential scanning calorimetry (DSC) studies did not show apparent difference in lower critical solution temperature (LCST) between normal and microgel-impregnated PNIPAAm hydrogels. The incorporating of PNIPAAm/PEG-DA microgels, however, significantly improved mechanical properties of modified hydrogels when comparing with a normal PNIPAAm hydrogel, although the tendency was not strictly proportional to the microgel amount. Based on the temperature-induced swelling ratio data as well as response kinetics, microgel-impregnated hydrogels exhibited improved thermosensitive characteristics in terms of higher equilibrium swelling ratio as well as faster response rates and the level of improvement depended on the amount of microgel impregnated.     

Thermosensitive phase transition kinetics of poly(N‐isopropylacryl amide‐co‐acrylamide) microgel aqueous dispersions

Thermosensitive poly(N‐isopropylacrylamide‐co‐acrylamide) microgel particles were prepared through precipitation polymerization. The diameters of the microgel particles were in the range of 220–270 nm and showed a monodispersion. The lower critical solution temperatures (LCST) of the microgel dispersions were measured by dynamic light scattering and turbidimetric analysis. The results indicated that the LCST increased with an increase of acrylamide (AAm) content in the copolymer composition. The kinetics of the thermosensitive phase transitions of the microgel particles were investigated by time‐course UV–vis spectroscopy. The results indicated that the higher the content of AAm in copolymer composition, the more time is required for equilibrium deswelling and the less time required for equilibrium swelling. In addition, the time required for equilibrium deswelling decreased with an increase of the content of the microgel particles in dispersions. By contrast, the time required for equilibrium swelling increased slightly. Thus, a suitable LCST and time required for equilibrium of phase transition can be achieved by adjusting the molar ratio of the comonomers in the microgels and the content of the microgel particles in dispersions. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

“Smart” nanoparticles: Preparation, characterization and applications

We review recent work on the preparation, characterization and application of “smart” microgel particles. A general feature of all systems under consideration here is their ability to react to external stimuli as e.g. the pH or the temperature in the system. Special emphasis is laid on our recent research work on the thermosensitive core-shell microgel particles, which are composed of a PS core and a cross-linked poly(N-isopropylacrylamide) (PNIPA) shell. Work done on these core-shell systems is compared to developments on the investigations of similar systems. A novel synthesis method, namely photo-emulsion polymerization, has been described for the preparation of monodisperse, thermosensitive core-shell particles. Cryogenic transmission electron microscopy (cryo-TEM) has recently been employed to investigate the morphology and the volume transition of the core-shell type microgels. This method furnishes information about the thermosensitive particles that had not been available through other methods employed in previous investigations. Very recently, it has been shown that these core-shell microgels can be used as “nanoreactors” for the immobilization of metal nanoparticles. The metal nanocomposite particles show “smart” catalytic behaviour, inasmuch as the catalytic activity of nanoparticles can be switched on and off through the volume transition that takes place within the thermosensitive shell of the carrier system. We also discuss possible future applications of these systems.     

Thermo-sensitive poly(N-vinylcaprolactam-co-acetoacetoxyethyl methacrylate) microgels. 3. Incorporation of polypyrrole by selective microgel swelling in ethanol-water mixtures

Behaviour of temperature-sensitive core-shell VCL/AAEM microgels has been studied in binary alcohol/water mixtures. Amount of alcohol in binary mixture influences strongly the swelling and thermo-sensitive properties of microgels. Alcohol induces swelling of VCL-rich microgel shell leading to larger dimensions of microgel particles and larger surface area. Under these conditions pyrrole polymerization was carried out, and the influence of pyrrole concentration, oxidant nature and temperature on morphology and properties of composite particles was investigated. Contrary to the polymerization in water medium, this selective swelling method gives possibility to increase three times loaded polypyrrole amount and maintain the stability of the colloidal system. It was found that in case when persulfate was applied as oxidant it is possible to vary effectively the particle size of composite microgels by changing the ethanol concentration in water. Contrary, when FeCl₃ was used as oxidant formation of secondary particles was detected leading to dispersions with bimodal particle size distribution. The conductivity of the composite particles was much higher if polypyrrole synthesis was carried out in pure water.     

Thermosensitive PMMA core/oligo(ethylene glycol)-based shell microgels as drug carriers in detoxification treatment

The core-shell structured polymer microgels were synthesized by coating the hydrophobic poly(methyl methacrylate) (PMMA) sphere cores with hydrophilic nonlinear poly(ethylene glycol)-based gel shell layer. The uniqueness of these core-shell microgels lies in the integration of the PMMA core microsphere with strong hydrophobicity and the novel oligo(ethylene glycol)-based gel layer with well-defined thermosensitivity for improving loading/release efficacy of two detoxification drugs (chlorpromazine and diltiazem). The hydrophilic shell is composed of hydrophilic copolymer of 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) with oligo(ethylene glycol) methyl ether methacrylates (MEO₅MA). It was found that the molar ratio of two shell monomers n(MEO₂MA)/n(MEO₅MA) of 1:6 was an ideal matching value for production of the P(MEO₂MA)/P(MEO₂MA-co-MEO₅MA) core-shell microgels with tunable volume phase transition temperature and excellent colloidal stability across the physiologically important temperature range. Moreover, chlorpromazine- and diltiazem-loaded microgels can show an obvious thermosensitive release and in vitro sustained-release characteristic up to 80 h.     

Ion-exchange and ion-transport in silica and sulphonated-silica (ormosil) hydrogels

The effects of organosulphonate groups on the ion-exchange and ion-transport properties of silica hydrogels have been investigated by using Ru(NH₃)₆³⁺, Ru(bpy)₃²⁺ and Fe(CN)₆³⁻ redox probes. Silica and sulphonated ormosil hydrogels were prepared by using tetramethyl orthosilicate as a silica precursor and 2(4-chlorosulphonylphenyl)ethyl-trichlorosilane to provide sulphonate functionality for ion-exchange and ion conductivity. Both gels act as cation-exchangers and exclude Fe(CN)₆³⁻. Partition coefficients are higher for the ormosil and for the more highly charged Ru(NH₃)₆³⁺ versus Ru(bpy)₃²⁺. Diffusion coefficients are higher for the unmodified silica, which is consistent with weaker interactions between the cationic probes and less anionic gel network.     

Temperature‐induced volume change and glucose sensitivity of poly[(N‐isopropylacry‐ lamide)‐co‐acrylamide‐co‐(phenylboronic acid)] microgels

Nearly monodisperse glucose‐sensitive poly[(N‐isopropylacrylamide)‐co‐acrylamide‐co‐(phenylboronic acid)] microgels were synthesized in aqueous media by the functionalization of poly[(N‐isopropylacrylamide)‐co‐acrylamide‐co‐(acrylic acid)] microgels with 3‐aminophenylboronic acid via carbodiimide coupling. The glucose‐sensitive and thermosensitive behaviour of the microgels was investigated using a dynamic light scattering technique. The introduction of the hydrophobic phenylboronic acid (PBA) group significantly decreases the temperature at which maximum volume change of the resultant microgel particles is observed. The glucose sensitivity of the PBA‐containing microgels relies on the stabilization of the charged phenylborate ions by binding with glucose, which can convert more hydrophobic PBA groups to the hydrophilic phenylborate ions. The effect of pH, ionic strength and PBA content on temperature‐induced volume change and glucose sensitivity was systemically studied. The effect of NaCl on the glucose sensitivity was also investigated at physiological pH and ionic strength. Copyright © 2011 Society of Chemical Industry     

Colloidal microgels as transdermal delivery systems

This paper presents a report of the synthesis of temperature-sensitive microgels based on a copolymer of butyl acrylate (10%) co-polyNIPAM (90%), in the presence of and in the absence of ibuprofen (IBU), methyl paraben (MP) and propyl paraben (PP), by a surfactant-free emulsion polymerisation in water. N^′,N^′-methylenebisacrylamide was used as a cross-linking agent and potassium persulphate as an initiator. Physicochemical properties of the microgels were determined using different techniques including dynamic light scattering and transmission electron microscopy. It is speculated that the microgel appearance is similar to a core-shell microgel, having in the core the complex IBU or MP or PP-butyl acrylate and in the shell poly(NIPAM). Permeation across a model silicone membrane and human skin was investigated over a range of temperatures (292–313 K). The transport rate of IBU and, PP from these poly(NIPAM) microgels is significantly reduced by two and one orders of magnitude, respectively, compared with the transport rate from saturated solutions. Such a reduction in flux was not however observed for MP.     

Equilibrium swelling of thermo-responsive core-shell microgels

Design of new routes for preparation of hydrogels with fast response and enhanced mechanical and physical properties requires adequate modeling of their swelling. A model is developed for the equilibrium swelling of thermo-responsive gels. A characteristic feature of the model is that it accounts for a strong increase in the elastic moduli above the volume phase transition temperature T_c driven by aggregation of hydrophobic segments into clusters that serve as extra physical bonds between chains. The model is applied to the analysis of swelling diagrams on poly(N-isopropylacrylamide) macroscopic gels, microgel latices, and core-shell microgels with rigid cores. Good agreement is shown between the experimental data and results of simulation. It is demonstrated that the elastic moduli of microgels are higher, while their degrees of swelling in the stress-free state are lower compared with those of macroscopic gels.     

Effects of end groups on the thermal response of poly(N‐isopropylacrylamide) microgels

Poly(N‐isopropylacrylamide) (PNIPAM) microgels were prepared through soap‐free emulsion polymerization using 2, 2′‐ azobisobutyronitrile and potassium persulfate as initiator respectively. The thermal response of microgels was researched by measuring the transmittance and the hydrodynamic diameter of the microgels at different temperatures. The result shows that the different structure of the end groups of polymer that come from residues of initiator result in the different thermal response of PNIPAM microgels. The LCST (lower critical solution temperature) of AIBN‐initiator microgels is 5°C lower than that of the KPS‐initiator microgels, whereas the AIBN‐initiated PNIPAM microgels have better thermal response sensitivity. The scanning electron microscope characterization shows that the morphology of AIBN‐initiated PNIPAM microgels is more regular than that of KPS‐initiated. Furthermore, the T_g of the microgels was measured by differential scanning calorimeter and the result indicates that the end groups influences the T_g of microgels severely. This work demonstrated that the hydrophobic end group coming from initiators can decreases the LCST of PNIPAM microgels and increases the thermal response sensitivity, which providing a newly simple but effective method to regulate the thermal response of PNIPAM microgels. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1164‐1171, 2013     

Morphology and drug release behavior of <Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide/acrylic acid copolymer as stimuli-responsive nanogels

Thermo- and pH-responsive N-isopropylacrylamide (NIPAM) nanogels can be obtained by copolymerization of acrylic acid (AA) comonomer through differential microemulsion polymerization. The effects of comonomer, cross-linker, surfactant contents, and water/oil ratio were preliminarily investigated by a 2⁴ full factorial design in order to eliminate the insignificant parameters from the polymerization analysis. The smallest poly(NIPAM-co-AA) nanogel particles were 40 ± 1 nm in diameter with 6 wt% of solid content and 98% conversion without coagulation. The comonomer amounts controlled the morphologies and LCST of the poly(NIPAM-co-AA) nanogels. The hairy microgels of poly(NIPAM-co-AA) with a 10:90 mol ratio of AA/ NIPAM had a lower critical solution temperature (LCST) of 6 °C. With an increase in the AA amount to a 17 mol ratio, the LCST increased to 27 °C, resulting in core-shell morphology. The morphology of resultant nanogels was characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and differential scanning calorimetry. Nuclear magnetic resonance spectroscopy was used to calculate the mole ratio of NIPAM and AA in resultant nanogels after dialysis. Both nanogel mole ratio and morphology effectively retained the cationic anti-cancer drug of methylene blue for several hours, an important basic requirement for a drug delivery system. Compared to core-shell microgels, a higher methylene blue release was obtained from the hairy microgels in simulated intestinal fluid.     

Thermo‐ and pH‐responsive microgels for controlled release of insulin

Microgel particles were prepared, made of hydroxypropylcellulose‐graft‐(acrylic acid) (HPC‐g‐AA) and acrylic acid(AA). The particles undergo reversible volume phase transitions in response to both pH and temperature changes while keeping the inherent properties of PAA and HPC‐g‐AA. Dynamic light scattering measurements reveal that the average hydrodynamic radius and hydrodynamic radius distributions of the microgel particles depend on temperature and pH. The microgels exhibit excellent pH sensitivity and a higher swelling ratio at higher pH in aqueous solution. In vitro release study shows that the amount of insulin released from the microgels is less at pH = 1.2 than at pH = 6.8. The results indicate that the resultant microgels seem to be of great potential for intelligent oral drug delivery. Copyright © 2012 Society of Chemical Industry     

Well-defined core-shell structures based on silsesquioxane microgels: Grafting of polystyrene via ATRP and product characterization

Silsesquioxane microgel nanoparticles characterized by low diameters (below 30 nm) and reduced polydispersity can be produced in an acid-catalyzed sol-gel process in an aqueous microemulsion. Suitable surface modification of such structures leads to macroinitiators for atom-transfer radical polymerization (ATRP). This polymerization method was applied in order to graft polystyrene chains onto the surface of the microgels. Well-defined structures exhibiting a core-shell architecture were produced with the M_w of grafted polymers ranging from 8.5 to about 30 kg/mol. The products were extensively characterized with light scattering, X-ray scattering, thermal analysis (TGA/DSC) and microscopy (TEM/SEM) to obtain information on parameters characterizing polystyrene brush. Polymer-grafted nanoparticles will be used for the modification of homopolymer and block copolymer matrices.     

On the structure of biocompatible,thermoresponsive poly(ethylene glycol) microgels

The aim of the present study is the preparation and characterization of microgel particles which are, contrary to other microgels, thermoresponsive as well as biocompatible. Hence, monodisperse p-MeO₂MA-co-OEGMA microgel particles were synthesized by precipitation polymerization. Swelling/deswelling behavior and the structure of poly(ethylene glycol) (PEG) based microgel particles were investigated. A combination of dynamic light scattering (DLS) and small angle neutron scattering (SANS) was used. Particle size and the volume phase transition temperature (VPTT) are adjustable by changing the amount of comonomer. SANS measurements indicate an inhomogeneous structure of the PEG microgels in the swollen state. At temperatures above the VPTT a compact structure was observed. An increase of the comonomer content leads to a densely packed core and a fuzzy shell in the swollen state. Additionally, nanodomains inside the polymer network were observed in the temperature range around the volume phase transition (VPT). Due to this heterogeneous structure in the swollen state two correlation lengths of the network fluctuations were observed.