Synthesis and thermo-responsive behavior of fluorescent labeled microgel particles based on poly(N-isopropylacrylamide) and its related polymers

Poly(N-isopropylacrylamide) (PNIPAM) microgel particles labeled with 3-(2-propenyl)-9-(4-N,N-dimethylaminophenyl)phenanthrene (VDP) as an intramolecular fluorescent probe were prepared by emulsion polymerization. The thermo-responsive behavior of the VDP-labeled PNIPAM microgel particles dispersed in water was studied by turbidimetric and fluorescence analyses. The transition temperature of the VDP-labeled PNIPAM microgel particles in water determined by turbidimetric analysis was ca. 32.5 °C. The wavelength at the maximum fluorescence intensity of the VDP units linked directly to the microgel particles dramatically blue-shifted around the transition temperature. In addition it gradually blue-shifted even below the transition temperature where there was no change observed in the turbidity. These findings suggest that the gradual shrinking of microgel particles occurs with increasing temperature and the subsequent dramatic shrinking results in the increasing in the turbidity. The transition temperatures of VDP-labeled poly(N-n-propylacrylamide) and poly(N-isopropylmethacrylamide) microgel particles determined by turbidimetric analysis were ca. 23 and ca. 42.5 °C, respectively, and their thermo-responsive behavior was similar to that for the VDP-labeled PNIPAM system. In these three systems the microenvironments around the fluorescent probes above the transition temperatures became more hydrophobic than those below the transition temperature, and the estimated values of microenvionmental polarity around the VDP units on their collapsed states were almost the same.     

Microfluidic fabrication of smart microgels from macromolecular precursors

Stimuli-responsive polymer microgels can be produced with exquisite control using droplet microfluidics; however, in existing methods, the droplet templating is strongly coupled to the material synthesis, because droplet solidification usually occurs through rapid polymerization immediately after the microfluidic droplet formation. This circumstance limits independent control of the material properties and the morphology of the resultant microgel particles. To overcome this limitation, we produce sensitive polymer microgels from pre-fabricated precursor polymers. We use microfluidic devices to emulsify semidilute solutions of crosslinkable poly(N-isopropylacrylamide) and solidify the drops via polymer-analogous gelation. This approach separates the polymer synthesis from the particle gelation and allows each to be controlled independently, thus enabling us to form monodisperse, thermo-responsive microgel particles with well-controlled composition and functionality. In addition, the microfluidic templating allows us to form complex particle morphologies such as hollow gel shells, anisotropic microgels, or multi-layered microgel capsules.     

多重响应壳聚糖微凝胶的制备及溶胀性

采用无皂乳液聚合法制备聚(N-异丙基丙烯酰胺)/壳聚糖微凝胶(PNIPAM/CS),透射电镜和动态光散射研究了微凝胶外貌形态及刺激响应性。结果显示,微凝胶颗粒呈球形,具有核、壳结构形态。加入壳聚糖对PNIPAM的体积相转变温度(VPTT)有影响,微凝胶VPTT随壳聚糖用量的增加向高温迁移,此结果与示差量热法(DSC)测定一致。不同pH条件下微凝胶粒径变化表明,颗粒直径随pH增大逐渐减小,至碱性又增大,显示明显的pH敏感性;相应颗粒Zeta电位逐渐减小,接近中性达到等电点,至碱性反转为负值,这一变化能对微凝胶pH敏感性进行合理解释。     

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。     

Volume phase transition of “smart” microgels in bulk solution and adsorbed at an interface: A combined AFM,dynamic light,and small angle neutron scattering study

In the present article the swelling behavior of copolymer microgel particles made of poly(N-isopropylacrylamide)-co-vinylacetic acid using dynamic light scattering (DLS), neutron scattering, and in situ atomic force microscopy (AFM) for various copolymerized amounts of vinylacetic acid (VA) (up to 2.5 mol%) under slightly acidic conditions is studied. The transition temperature of these microgel particles is found to be ≈32.5 ± 1 °C, independent of the VA content. Microgel particles adsorbed onto a solid substrate display a similar volume phase transition as their dissolved counterparts. However, their swelling capacity is reduced by approximately one order of magnitude compared to the bulk value. Nevertheless, the observed effect still is sufficiently large to be exploited for the use of these particles in sensors or as nanoactuators. In addition it can be concluded that the continuous character of the transition observed in solution does not arise from the polydispersity of the particles but can be attributed to the heterogeneity inside each individual microgel particle. Finally, AFM images reveal a pattern on the surface of the collapsed particles, which we attribute to globules formed by collapsed dangling polymer chains. In solution these dangling ends form a brush contributing to the hydrodynamic dimensions of the microgels.     

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.     

Thermo-responsive mixed-matrix hollow fiber membranes

Up to date, preparation of thermo-responsive mixed-matrix membranes (MMM) has only be described as small scale flat membranes or multi-step processes for hollow fiber membranes. In this work, the development of thermo-responsive MMM hollow fibers composed of polyethersulfone as membrane polymer and poly(N-isopropylacrylamide) (PNIPAM) microgel particles via the wet spinning process is presented. PNIPAM particles are synthesized with (NP-S, z_{avg 20°C} = 105 nm) and without (NP-L, z_{avg 20°C} = 250 nm) sodium dodecyl sulfate and their thermo-responsive behavior is characterized by dynamic light scattering. Particle size (NP-S, NP-L), particle content (10%, 15%) and the extrusion pressure in the wet spinning process (1.0–3.0 bar) are investigated as experimental parameters. Reversible thermo-responsive behavior of the hollow fibers is demonstrated by water permeability measurements at different temperatures (20 and 50°C). The largest switching factors (R) are observed for the hollow fibers containing NP-L. For 15% NP-L and 1 bar extrusion pressure, water permeances between 0.5 and 6.0 L m⁻² h⁻¹ bar⁻¹ are observed, corresponding to R = 12 and a dextran (500 kDa) rejection of 91% at 25°C.     

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.     

聚（N-异丙基丙烯酰胺）/聚丙烯酸半互穿网络微凝胶的合成及表征

利用IPN技术合成了一种具有温度和pH双重敏感性的聚（N-异丙基丙烯酰胺）/聚丙烯酸半互穿网络微凝胶（PNIPAM/PAAc semi-IPN）。这种微凝胶在酸性条件下发生典型的体积相转变;而在弱碱性条件下,当温度低于聚（N-异丙基丙烯酰胺）（PNIPAM）微凝胶的体积相转变温度（VPTT）时,微凝胶的粒径随着温度的上升而增大,当温度达到VPTT后,粒径突然急剧减小,并随着温度的逐渐上升而减小,最终趋向平衡。     

智能膜开关尺寸与孔径的匹配性对膜响应性能的影响规律

智能膜的响应性能是其主要性能之一。本文借助计算流体力学（CFD）模拟,以孔壁排布有聚N-异丙基丙烯酰胺（PNIPAM）智能微球的单直膜孔为模型,定量系统地考察了智能微球的响应倍数以及微球尺寸与膜孔径的匹配性对膜温度响应性能的影响规律,并通过实验验证了模拟结果的可靠性。CFD模拟结果表明,当智能开关与膜孔径的相对比值一定时,温度响应开关系数随着微球响应倍数的减小而逐渐增大。当相对比值小于0.4时,实测的温度响应开关系数与固载量100%的模拟结果相吻合;而当相对比值大于0.4时,其与固载量为67%的模拟结果相吻合。通常当相对比值在0.4～0.65之间时,智能膜可以同时获得良好的温度响应性能和稳定的渗透性能。该研究结果可望为设计和制备高性能智能膜提供理论指导和实验基础。     

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.     

Drug release kinetics from monolayer films of glucose-sensitive microgel

To study the drug release behaviors of glucose-sensitive poly(N-isopropylacrylamide-co-3-acrylamidophenylboronic acid) (P(NIPAM-PBA)) microgels, P(NIPAM-PBA) microgel monolayers were prepared by the modification of poly(N-isopropylacrylamide-co-acrylic acid) microgel monolayers with 3-aminophenylboronic acid under EDC catalysis. Alizarin Red S (ARS) and FITC-labeled insulin (FITC-insulin) were loaded in the monolayers respectively. Their release kinetics under various conditions were measured. For both drugs, at low temperature, the drug release can be described as passive diffusion of the drugs. At temperature higher than the phase transition temperature, however, the drugs are released via a “squeeze-out” mechanism. Glucose-regulated release for both drugs was observed. At all temperatures glucose enhances the release of ARS because it competes with ARS for binding with PBA groups. For FITC-insulin, glucose enhances its release at 4 °C, but retards at 37 °C. These results will guide the design of self-regulated insulin release systems based on P(NIPAM-PBA) microgels.     

Glass and Jamming Rheology in Soft Particles Made of PNIPAM and Polyacrylic Acid

The phase behaviour of soft colloids has attracted great attention due to the large variety of new phenomenologies emerging from their ability to pack at very high volume fractions. Here we report rheological measurements on interpenetrated polymer network microgels composed of poly(N-isopropylacrylamide) (PNIPAM) and polyacrylic acid (PAAc) at fixed PAAc content as a function of weight concentration. We found three different rheological regimes characteristic of three different states: a Newtonian shear-thinning fluid, an attractive glass characterized by a yield stress, and a jamming state. We discuss the possible molecular mechanisms driving the formation of these states.     

沉淀聚合法制备VCL／NVP温敏型微凝胶及其性能研究

用沉淀聚合法,以N-乙烯基己内酰胺（VCL）和N-乙烯基吡咯烷酮（NVP）为共聚单体、N,N-亚甲基双丙烯酰胺（MBA）为交联剂,通过改变交联剂的量制备了-系列不同粒径的温敏型微凝胶。用纳米颗粒力度分析仪（DLS）和原子粒显微镜（AFM）对凝胶进行了表征。结果表明：粒子为球型单分散;在15—55℃范围内凝胶粒径随温度升高而减小,具有温度敏感性,最低临界转变温度（LCST）为35℃;交联剂的量不改变最低临界转变温度,只改变粒子大小。     

Synthesis and characterisation of thermo-responsive poly(N,N′-diethylacrylamide) microgels

Poly(N,N-diethylacrylamide) microgels (diameter < 1000 nm) with narrow size distribution were synthesised by Surfactant-Free Emulsion Polymerisation at 70 °C in aqueous solution using potassium persulphate as initiator. The gels were characterised in comparison to the corresponding poly(N-isopropylacrylamide) microgels. They showed reversible collapse upon thermo-stimulation with a critical temperature between 28 and 30 °C, i.e. slightly below the critical temperature of the corresponding linear molecules. The average particle diameter as determined by electron microscopy decreased with increasing stirring rate adjusted during synthesis, although the effect was less straightforward for the poly(N,N-diethylacrylamide) microgels than for the poly(N-isopropylacrylamide) ones. In microgel preparations produced at the highest stirring speeds, the presence of small particles was observed, possibly a manifestation of residual ‘precursor particles’. A first characterisation of the biocompatibility of the gels was done by the WST-1 viability and the LDH cytotoxicity assays using the human breast cancer cell line MCF-7 (ATCC HTB-22) and a human T leukaemia cell line (Jurkat, ATCC TIB-125) as probes. No short-term effects (time span covered in the investigation <4 h) of the microgels on cell viability could be observed when the cell were incubated with the gels at 37 °C, i.e. above the critical temperature. At 22 °C and for microgel concentrations above 1 mg/mL some cytotoxicity was observed. In general the cytotoxicity was more pronounced for the poly(N-isopropylacrylamide) microgels than for the poly(N,N-diethylacrylamide) ones.     

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.     

Microgel/clay nanohybrids as responsive scavenger systems

Microgel-clay composite particles were prepared by one-step surfactant-free precipitation polymerization. Laponite nanoparticles present in the reaction mixture become encapsulated during the microgel formation process. Microgel-clay composites based on poly(N-vinylcaprolactam-co-acetoacetoxyethyl methacrylate) containing different amount of incorporated clay nanoparticles were synthesized. The clay content was varied from 2 wt% to 18 wt%. The extremely high incorporation efficiency of the clay nanoparticles into microgels was detected. The size of the hybrid microgels was decreased from 700 nm to 100 nm by increase of the clay concentration in the reaction mixture. Obtained hybrid microgels exhibit negative surface charge and excellent colloidal stability. Microgel-clay composite particles display temperature-sensitive behaviour in water. The swelling degree of the hybrid microgels decreases with increase of the clay loading. Microgel-clay composite particles exhibit temperature-controlled uptake of the cationic dye, Methylene blue, and can be used as scavenger systems in aqueous media.     

“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.     

聚(N-异丙基丙烯酰胺)微凝胶的流变性能研究

首先采用无皂乳液聚合法成功制备出粒径均匀的聚N-异丙基丙烯酰胺(PNIPAM)微凝胶,利用动态光散射法(DLS)测得微凝胶的粒径随温度的升高而下降,结果表明:PNIPAM微凝胶具有明显的温度敏感性。利用旋转流变仪对微凝胶分散液的稳态和动态粘弹性进行了研究,结果表明:当温度低于体积相转变温度(VTPP)时,微凝胶呈现出剪切变稀的特性;应力、应变保持不变,随着温度的升高及温度不变,随着频率的增加微凝胶都由液态变成了粘弹性固体,这可能是由于出现了三维逾渗网络结构造成的。     

Microgel/SiO2 hybrid colloids prepared using a water soluble silica precursor

In the present work we demonstrate that functional polymer microgels may act as smart self-catalyzing system inducing controlled formation of silica nanoparticles inside the polymer network and formation of hybrid colloids. We synthesized a water soluble silica precursor PEG-PEOS via post-modification of hyperbranched poly(ethoxysiloxane) (PEOS) with poly(ethylene glycol) monomethyl ether. We used poly(N-vinylcaprolactam)-based microgel functionalized with imidazole and β-diketone groups as a matrix for biomimetic deposition of silica. Composite microgel particles containing silica nanoparticles (up to 20 wt.-%) have been prepared by simultaneous PEG-PEOS conversion and silica deposition in the microgels. TEM studies indicate the infiltration of silica nanoparticles (～10 nm) inside the corona region of the microgels due to the strong acid–base interaction between the acidic silica and basic imidazole groups. The resulting composite particles were found to be colloidally stable and no aggregation was observed even after months of storage. The incorporation of silica nanoparticles increased the rigidity of the microgel particles and reduced their thermal sensitivity.