Efficient synthesis of sterically stabilized pH-responsive microgels of controllable particle diameter by emulsion polymerization

Emulsion polymerization of 2-vinylpyridine (2VP) in the presence of divinylbenzene (DVB) cross-linker, a cationic surfactant, and a hydrophilic macromonomer, monomethoxy-capped poly(ethylene glycol) methacrylate (PEGMA), at around neutral pH and 60 degrees C afforded near-monodisperse, sterically stabilized latexes at approximately 10% solids. Judicious selection of the synthesis parameters enabled the mean latex diameter to be varied over an unusually wide range for one-shot batch syntheses. Scanning electron microscopy studies confirmed near-monodisperse spherical morphologies, with mean weight-average particle diameters ranging from 370 to 970 nm depending on the initiator, polymeric stabilizer, and surfactant concentrations. Particle sizing studies were also conducted using disk centrifuge photosedimentometry and dynamic light scattering and gave similar data. These lightly cross-linked latexes acquired cationic microgel character at low pH, as expected. The critical pH for this latex-to-microgel transition was around pH 4.1 at 1.0 wt % DVB, which is significantly lower than the pKa of 4.92 estimated for linear P2VP homopolymer by acid titration. 1H NMR and aqueous electrophoresis studies indicated that substantial swelling occurred at low pH due to protonation of the 2VP groups, while dynamic light scattering (DLS) studies indicated volumetric swelling ratios of up to 3 orders of magnitude, depending on the initial latex diameter. Systematic variation of the degree of cross-linking led to a monotonic decrease in the pKa values of the P2VP latexes (as judged by acid titration) and also the critical swelling pH (as judged by visual inspection). This was attributed to the increasingly branched nature of the P2VP chains in their swollen microgel form. Preliminary studies of the kinetics of acid-induced swelling were also conducted using the pH jump method in conjunction with a stopped-flow apparatus. These P2VP latexes swell significantly faster than P2VP latexes described in the literature and the characteristic time scales observed in the present study are much closer to those predicted by the Tanaka equation.     

Swelling behavior of PMMA-g-PEO microgel particles by organic solvents

Aqueous dispersions of cross-linked poly(methylmethacrylate)-g-poly(ethylene oxide) [PMMA-g-PEO] microgel particles have been prepared from mixtures of methylmethacrylate [MMA] and MMA-PEO macromonomer, with ethylene glycol dimethacrylate [EGDM] as the cross-linking monomer (0.2-0.5% wt%). The hydrodynamic radius of these (unswollen) microgel particles ranged from 73 to 85 nm, and the particles were essentially monodisperse with regard to their size distribution. Their swelling behavior has been investigated in the presence of both water-miscible and water-immiscible organic solvents. In general, with the addition of a water-miscible solvent, deswelling behavior was observed. However, the microgel particles were swollen on addition of 1,4-dioxan, which is a good solvent for PMMA. With water-immiscible organic solvents, the extent of swelling depended on the solvency properties of the organic liquid for PMMA. In the presence of benzene, the somewhat large increases in particle size have been attributed to weak flocculation. This has been assumed from an estimate of the van der Waals attraction energy between the swollen microgel particles.     

Swelling and deswelling of adsorbed microgel monolayers triggered by changes in temperature, pH, and electrolyte concentration

The formation and characterization of close-packed monolayers of negative, poly(N-isopropylacrylamide)-based microgel particles onto positively charged silicon wafers is described. The silicon wafers were rendered positive by first oxidizing their surface to silica and then adsorbing a layer of poly(ethyleneimine). The thickness of the deposited microgel monolayers (under aqueous conditions) has been determined by spectroscopic ellipsometry as a function of temperature (20-60 degrees C), pH (3-8), and added NaCl concentration (0-1 M). No actual desorption of the microgel particles was evident on changing the conditions, but a swelling/deswelling transition was observed around 32 degrees C. The thickness of the monolayer has been compared with the hydrodynamic diameter of the free microgel particles, dispersed in aqueous solution. For the poly(N-isopropylacrylamide) microgel particles, without any bulk ionisable comonomer groups present, the temperature dependence of the ellipsometric thickness of the monolayer mirrors closely that of the hydrodynamic diameter of the free particles. When ionizable (-COOH) groups are introduced into the microgel particles, however, this correspondence is largely lost because the microgel particles forming the deposited monolayer now contract strongly onto the oppositely charged substrate surface.     

Synthesis and characterization of novel pH-responsive microgels based on tertiary amine methacrylates

Emulsion polymerization of 2-(diethylamino)ethyl methacrylate (DEA) in the presence of a bifunctional cross-linker at pH 8-9 afforded novel pH-responsive microgels of 250-700 nm diameter. Both batch and semicontinuous syntheses were explored using thermal and redox initiators. Various strategies were evaluated for achieving colloidal stability, including charge stabilization, surfactant stabilization, and steric stabilization. The latter proved to be the most convenient and effective, and three types of well-defined reactive macromonomers were examined, namely, monomethoxy-capped poly(ethylene glycol) methacrylate (PEGMA), styrene-capped poly[2-(dimethylamino)ethyl methacrylate] (PDMA50-St), and partially quaternized styrene-capped poly[2-(dimethylamino)ethyl methacrylate] (10qPDMA50-St). The resulting microgels were pH-responsive, as expected. Dynamic light scattering and 1H NMR studies confirmed that reversible swelling occurred at low pH due to protonation of the tertiary amine groups on the DEA residues. The critical pH for this latex-to-microgel transition was around pH 6.5-7.0, which corresponds approximately to the known pKa of 7.0-7.3 for linear PDEA homopolymer. The microgel particles were further characterized by electron microscopy and aqueous electrophoresis studies. Their swelling and deswelling kinetics were investigated by turbidimetry. The PDEA-based microgels were compared to poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) microgels prepared with identical macromonomer stabilizers. These PDPA-based microgels had a lower critical swelling pH of around pH 5.0-5.5, which correlates with the lower pKa of PDPA homopolymer. In addition, the kinetics of swelling for the PDPA microgels was somewhat slower than that observed for PDEA microgels; presumably this is related to the greater hydrophobic character of the former particles.     

N‐vinylcaprolactam‐based microgels: Effect of the concentration and type of cross‐linker

New microgel particles produced by using N‐vinylcaprolactam (VCL) and poly(ethylene glycol) diacrylate (PEGDA) or N,N′‐methylenbisacrylamide (BA) were synthesized in a batch reactor. The influence of the concentration and type of crosslinker on polymerization kinetics and colloidal characteristics of such temperature‐sensitive particles was studied. The partial and total conversion evolutions of VCL, PEGDA, and BA were determined by quantitative ¹H NMR and the average diameters of microgel particles together with the swelling–deswelling behavior were analyzed by means of photon correlation spectroscopy (PCS). Partial and total conversions, final average diameters at collapsed state, and the swelling–deswelling behavior varied as a function of the type of crosslinker. These results were attributed to the higher solubility and stabilizing ability of PEGDA compared with that of BA. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2766–2775, 2008     

Metal nanocrystals incorporated within pH-responsive microgel particles

Cross-linked sterically stabilized latexes of approximately 250 nm diameter were synthesized by emulsion polymerization of 2-(diethylamino)ethyl methacrylate using a bifunctional oligo(propylene oxide)-based diacrylate cross-linker and a poly(ethylene oxide)-based macromonomer as the stabilizer at pH 9. These particles exhibit reversible swelling properties in water by adjusting the solution pH. At low pH, they exist as swollen microgels as a result of protonation of the tertiary amine units. Deswelling occurs above pH 7 [the effective pK(a) of poly(2-(diethylamino)ethyl methacrylate)], leading to the formation of the original compact latex particles. The swollen microgels can be used as nanoreactors: efficient impregnation with Pt nanoparticles can be achieved by incorporating precursor platinum compounds, followed by metal reduction. Dynamic light scattering was used to compare two methods of Pt nanoparticle impregnation with respect to the size and stability of the final Pt-loaded microgel particles. In the first method, the H2PtCl6 precursor was added to hydrophobic latex particles at high pH, followed by metal reduction. In the second method, H2PtCl6 was added to hydrophilic swollen microgel particles at low pH, and then this metal salt was reduced in situ using NaBH4 and the pH was raised by the addition of base. Both the Pt salt-loaded (metalated) microgels and the final Pt nanoparticle-loaded microgels had well-defined structures that were independent of the synthesis route. Polymer-metal interactions were investigated by UV-visible absorption spectroscopy, which confirmed that the Pt salt was completely reduced to zero-valent Pt. Transmission electron microscopy and X-ray diffraction studies verified the formation of nanometer-sized Pt nanoparticles within these microgels, which can be used as recoverable colloidal catalyst supports for various organic reactions.     

Transport of poly-L-lysine into oppositely charged poly(acrylic acid) microgels and its effect on gel deswelling

The interaction between poly-L-lysine (pLys) and oppositely charged poly(acrylic acid) (pAA) microgels (? approximately 80-120 microm) was studied by micromanipulator-assisted light microscopy and confocal laser scanning microscopy. The aim of this study was to investigate effects of peptide size, pH, and salt concentration on binding, transport, and distribution of pLys in pAA microgel particles and thereby also to outline the details of the gel deswelling in response to pLys binding and incorporation. Both peptide distribution and gel deswelling kinetics were found to be strongly influenced by the pLys molecular weight, originating partly from limited entry of large peptides into the gel particle core. Also pH was shown to influence both deswelling and pLys incorporation kinetics, with a decreased deswelling rate observed with increasing pH. These effects are determined by a complex interplay between the pH-dependence of both pLys and the gel network, also influencing volume transitions of the latter. Finally, salt concentration was shown to have a significant effect on both gel deswelling rate and pLys transport, with an increased electrolyte concentration resulting in decreased deswelling rate but also in an increased peptide transport rate within the microgel particles.     

Effect of initial substrate concentration of the Belousov-Zhabotinsky reaction on self-oscillation for microgel system

Self-oscillation for the microgel particles ( approximately 200 nm in diameter) was studied by changing initial substrate concentrations (i.e., malonic acid, sodium bromate, and nitric acid) of the Belousov-Zhabotinsky (BZ) reaction that is used for chemical energy for the self-oscillation. The cross-linked microgels are composed of N-isopropylacrylamide and ruthenium tris(2,2'-bipyridine), Ru(bpy) 3, which is a catalyst for the BZ reaction. Comparing with the homogeneous, stirred solution of the bulk solution for the BZ reaction, swelling/deswelling oscillation of the microgels showed longer induction period, different dependence of initial substrate concentrations on oscillation period, and different oscillation rhythm. The change in oscillation for the microgels can be understood by considering the microgel network effect.     

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.     

Impact of Polymer Network Inhomogeneities on the Volume Phase Transition of Thermoresponsive Microgels

Thermoresponsive polymer gels exhibit pronounced swelling and deswelling upon changes in temperature, rendering them attractive for various applications. This transition has been studied extensively, but only little is known about how it is affected by nano‐ and micrometer‐scale inhomogeneities in the polymer gel network. In this work, droplet microfluidics is used to fabricate microgel particles of strongly varying inner homogeneity to study their volume phase behavior. These particles exhibit very similar equilibrium swelling and deswelling independent of their inner inhomogeneity, but the kinetics of their volume phase transition is markedly different: while gels with pronounced micrometer‐scale inhomogeneity show fast and affine deswelling, homogeneous gels shrink slowly and in multiple steps.     

Effects of pH and salt concentration on oil-in-water emulsions stabilized solely by nanocomposite microgel particles

Aqueous dispersions of lightly cross-linked poly(4-vinylpyridine)/silica nanocomposite microgel particles are used as a sole emulsifier of methyl myristate and water (1:1 by volume) at various pH values and salt concentrations at 20 degrees C. These particles become swollen at low pH with the hydrodynamic diameter increasing from 250 nm at pH 8.8 to 630 nm at pH 2.7. For batch emulsions prepared at pH 3.4, oil-in-water (o/w) emulsions are formed that are stable to coalescence but exhibit creaming. Below pH 3.3, however, these emulsions are very unstable to coalescence and rapid phase separation occurs just after homogenization (pH-dependent). The pH for 50% ionization of the pyridine groups in the particles in the bulk (pK(a)) was determined to be 3.4 by acid titration measurements of the aqueous dispersion. Thus, the charged swollen particles no longer adsorb at the oil-water interface. For continuous emulsions (prepared at high pH with the pH then decreased abruptly or progressively), demulsification takes place rapidly below pH 3.3, implying that particles adsorbed at the oil-water interface can become charged (protonated) and detached from the interface in situ (pH-responsive). Furthermore, at a fixed pH of 4.0, addition of sodium chloride to the aqueous dispersion increases the degree of ionization of the particles and batch emulsions are significantly unstable to coalescence at a salt concentration of 0.24 mol kg(-1). The degree of ionization of such microgel particles is a critical factor in controlling the coalescence stability of o/w emulsions stabilized by them.     

甲基丙烯酸烷酯、甲基丙烯酰胺及丙烯酸与4,4′-二(甲基丙烯酰胺基)偶氮苯交联共聚凝胶的消溶胀动力学

研究了甲基丙烯酸十二烷或丁酯、甲基丙烯酰胺及丙烯酸与 4 ,4′ 二 (甲基丙烯酰胺基 )偶氮苯交联共聚凝胶的消溶胀动力学 .这类凝胶在pH7 4或pH8 0的缓冲溶液中达到溶胀平衡后 ,将其分别转入pH2 2和pH4 0的缓冲溶液中 .凝胶的消溶胀过程表现出两种情况 :一种是凝胶直接发生消溶胀 ,另一种是凝胶首先经历一个短时的溶胀然后再发生消溶胀 ,呈明显不同的两种消溶胀机制 .前者在单位时间内释水量 [(Ht-H0 ) t]的倒数与消溶胀时间有一个良好的线性相关性 ;而后者在单位时间内含水量 [Ht t]平方根的倒数与消溶胀时间有一个良好的线性相关性 .     

Balance of hydrophobic and electrostatic forces in the pH response of weak polyelectrolyte capsules

A detailed study of the role of solution pH and ionic strength on the swelling behavior of capsules composed of the weak polyelectrolytes poly(4-vinylpyridine) (P4VP) and poly(methacrylic acid) (PMA) with different numbers of layers was carried out. The polyelectrolyte layers were assembled onto silicon oxide particles and multilayer formation was followed by zeta-potential measurements. Hollow capsules were investigated by scanning electron microscopy and atomic force microscopy. The pH-dependent behavior of P4VP/PMA capsules was probed in aqueous media using confocal laser scanning microscopy. All systems exhibited a pronounced swelling at the edges of stability, at pHs of 2 and 8.1. The swelling degree increased when more polymer material was adsorbed. The swollen state can be attributed to uncompensated positive and negative charges within the multilayers, and it is stabilized by counteracting hydrophobic interactions. The swelling was related to the electrostatic interactions by infrared spectroscopy and zeta-potential measurements. The stability of the capsules as well as the swelling degree at a given pH could be tuned, when the ionic strength of the medium was altered.     

Review on the dynamics and micro-structure of pH-responsive nano-colloidal systems

This review presents an overview on the research on pH-responsive microgel particles in the last 10 years. Microgels are cross-linked latex particles that are swollen in a good solvent. Significant quantitative studies have been conducted to investigate the swelling behavior (microscopic) and rheological (macroscopic) properties of the pH-responsive microgel particles as a function of neutralization degree, ionic strength, and cross-linked density. Mono-dispersed, alkali-swellable microgels containing carboxylic acid lattices, whose properties display extreme pH sensitivity in water is considered in detail in terms of swelling behavior and rheological properties. Their stability in solution and ability to undergo reversible volume phase transitions in response to pH makes them ideal model systems for the development of a semi-empirical as well as theoretical approach for predicting the viscosity of dilute and concentrated hard and soft sphere systems. The review concludes with a discussion of some recent applications of pH-responsive microgel particles.     

Swelling Kinetics of Microgels Embedded in a Polyacrylamide Hydrogel Matrix

Composite hydrogels—macroscopic hydrogels with embedded microgel particles—are expected to respond to external stimuli quickly because microgels swell much faster than bulky gels. In this work, the kinetics of the pH‐induced swelling of a composite hydrogel are studied using turbidity measurements. The embedded microgel is a pH‐ and thermosensitive poly(N‐isopropylacrylamide‐co‐acrylic acid) microgel and the hydrogel matrix is polyacrylamide. A rapid pH‐induced swelling of the embedded microgel particles is observed, confirming that composite hydrogels respond faster than ordinary hydrogels. However, compared with the free microgels, the swelling of the embedded microgel is much slower. Diffusion of OH^? into the composite hydrogel film is identified as the main reason for the slow swelling of the embedded microgel particles, as the time of the pH‐induced swelling of this film is comparable to that of OH^? diffusion into the film. The composition of the hydrogel matrix does not significantly change the characteristic swelling time of the composite hydrogel film. However, the swelling pattern of the film changes with composition of the hydrogel matrix.     

Direct imaging and spectroscopic characterization of stimulus-responsive microgels

Scanning transmission X-ray microscopy has been employed to visualize pH-responsive acid-swellable microgel particles directly in their swollen state in aqueous acidic solution. Moreover, NEXAFS studies confirm that the nitrogen atoms of these cationic microgel particles are completely protonated at low pH.     

Swelling behaviors of thermoresponsive hydrogels cross-linked with acryloyloxyethylaminopolysuccinimide

Based on a biodegradable cross-linker, acryloyloxyethylaminopolysuccinimide (AEA-PSI), a series of looser cross-linked poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their water content, swelling/deswelling kinetics, and the morphology of the gels were investigated. The swelling behaviors of AEA-PSI-cross-linked P(NIPAAm/AAc) hydrogels were investigated in Dulbecco’s phosphate-buffered saline (pH = 7.4), in the distilled water, and in the simulated gastric fluids (pH = 1.2), respectively. The water contents of the hydrogels were controlled by the monomer molar ratio of NIPAAm/AAc, swelling media, and the temperature. In the swelling kinetics, all the dried hydrogels exhibited fast swelling behavior, and the swelling ratios were influenced significantly by the amounts of AEA-PSI and AAc content. The deswelling kinetics of the hydrogel were independent of the content of AAc and cross-linker. Lastly, the morphology of the hydrogels was estimated by the field scan electron microscopy.     

Some anomalous effects of sodium ions on the electrophoretic mobility and heteroaggregation of microgel particles

Experiments on the kinetics of heteroaggregation between oppositely charged particles, using both dynamic light scattering and turbidity methods, are reported. The negatively charged particles were cross-linked poly( [Formula: see text] -isopropylacrylamide) [PNIPAM] microgel particles, prepared using a carboxylic-acid-based initiator; these particles are swollen at room temperature. The positive particles were poly(4-vinylpyridine) [P4VP] particles, prepared using an amidinium-based initiator; such particles do not respond to temperature changes but do swell below pH approximately 4, where the pyridine moieties become protonated. As expected, the rate of heteroaggregation was shown to be largely independent of added salt concentration (up to approximately 20 mM), for a variety of alkali metal chlorides (MCl, where M = Li, Na, K, or Rb). However, an unexpected, significant decrease in the aggregation rate was observed at certain specific sodium chloride concentrations (typically at approximately 1 and also approximately 4 mM). Similar effects were not seen with the other alkali metal chloride salts. This strange effect was eventually attributed to the fact that the net charge on the positively charged P4VP particles had been reduced by the adsorption of (anionic) silicate species leached from the glassware container. Sodium silicates are known to be significantly more soluble than those of the other alkali metal ions, particularly at high pH. Moreover, P4VP particles dispersed in water, ostensibly at neutral pH, do buffer the aqueous medium to pH values around 9 or higher. This mechanism was confirmed by determining the electrophoretic mobility of the P4VP particles as a function of pH in the presence of the various alkali metal chloride salts. The mobility remained positive in 1 mM salt solutions over the pH range 3 to 11 for all the salts, except for sodium chloride; in that case the mobility reversed sign at alkaline pH values. A similar effect was observed for a cationic polystyrene latex sample, prepared with the same amidinium-based initiator. These experiments demonstrate the importance of soluble silicates, leached from glass storage vessels, particularly in the presence of sodium ions. Needless to say, the "anomalous" effects disappeared when plastic storage vessels were used in place of the glass ones.     

N‐vinylcaprolactam‐based microgels for biomedical applications

Three types of poly(N‐vinylcaprolactam)‐based temperature‐sensitive microgel particles were synthesized by emulsion polymerization. The uptake of a model drug (calcein) into the particles was analyzed in terms of the amount of calcein absorbed and equilibrium–swelling degree. By incubating the microgels with primary neuronal cell cultures of embrionary rats, cell viability and biocompatibility tests were carried out. The results show that the driving force for the model drug to penetrate into the microgel particles is H‐bonding associations. On the other hand, cell death was microgel concentration and incubation period dependent. Microgels can be stored in a dried state and resuspended in water when necessary without changing their swelling–deswelling ability. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1173–1181, 2010