pH-responsive Microgels Research Articles

In situ observations of adsorbed microgel particles.

The formation and morphological changes of a pH-responsive microgel layer on silica and mica were studied by tapping mode atomic force microscopy. First, lightly cross-linked, sterically-stabilised poly(2-vinylpyridine) (P2VP) particles were adsorbed in their non-solvated latex form at pH 4.8 to produce a structurally-disordered monolayer that covers the entire substrate. Addition of acid to this particulate film induces a latex-to-microgel transition at pH 3.0, causes particle swelling (and also some desorption) and produces a uniform, swollen film with localised hexagonal packing. Returning to pH 4.8 causes partial microgel deswelling to form individual oblate spheroidal P2VP latex particles, which retain the localised order previously induced by swelling. The swelling and collapse of this P2VP film was reversible during subsequent pH cycles, with no further desorption observed. The adsorbed amount of P2VP microgel/latex was quantified at each pH by determining the surface density and dimensions of the adsorbed particles. These measurements allow the microgel surface excess to be calculated for the first time. The initial adsorbed amount is less than that predicted by the standard Random Sequential Adsorption model (RSA) for hard particle adsorption, and is explained by the unexpected deformation of these high Tg particles due to their strong electrostatic attraction to the solid-liquid interface.

A study of pH-responsive microgel dispersions: from fluid-to-gel transitions to mechanical property restoration for load-bearing tissue.

An interesting, and potentially important, challenge for colloid scientists is to design injectable dispersions that enable repair of damaged and degenerated tissue. This work presents a study of the ability of pH-responsive microgel particles to restore the mechanical properties of load-bearing soft tissue. Microgel particles are cross-linked polymer colloid particles that are swollen with solvent. The first part of the study consists of an investigation of the pH-triggered swelling of poly(EA/MAA/BDDA) (ethylacrylate, methacrylic acid and 1,4-butanediol diacrylate) microgel particles using photon correlation spectroscopy (PCS) measurements. The concentrated dispersions exhibit a strong fluid-to-gel transition when the pH is increased to above 6.0, i.e., above this pH they form gelled microgel dispersions. The swelling data are used to aid interpretation of the pH-triggered changes in the gel modulus, as probed using dynamic rheology. The second part of the study involves an investigation of the mechanical properties of artificially degenerated, model intervertebral discs (IVDs) containing gelled microgel dispersions. High concentration microgel dispersions were injected as fluids into the interior of degenerated IVDs and the pH increased by subsequent alkaline solution injection to cause particle swelling and dispersion gelation. Uniaxial compression data measured for the IVDs containing injected microgel dispersions indicate that the pH-induced particle swelling of the microgel restores the mechanical properties of degenerated IVDs to values similar to those measured for normal, non-degenerated, IVDs.

Application of drug selective electrode in the drug release study of pH-responsive microgels

The colloidal phenomenon of soft particles is becoming an important field of research due to the growing interest in using polymeric system in drug delivery. Previous studies have focused on techniques that require intermediate process step such as dialysis or centrifugation, which introduces additional errors in obtaining the diffusion kinetic data. In this study, a drug selective electrode was used to directly measure the concentration of procaine hydrochloride (PrHy) released from methacrylic acid–ethyl acrylate (MAA–EA) microgel, thereby eliminating the intermediate process step. PrHy selective membrane constructed using a modified poly (vinyl chloride) (PVC) membrane and poly (ethylene-co-vinyl acetate-co-carbon monoxide) as plasticizer exhibited excellent reproducibility and stability. The response was reproducible at pH of between 3 to 8.5 and the selectivity coefficients against various organic and inorganic cations were evaluated. Drug release was conducted using the drug electrode under different pHs and the release rate increased with pH. The release behavior of the system under different pH exhibited obvious gradient release characteristics.

Synthesis and Characterization of Poly(vinylcaprolactam)-Based Microgels Exhibiting Temperature and pH-Sensitive Properties

Novel temperature- and pH-responsive microgels based on poly(vinylcaprolactam-co-acetoacetoxy methacrylate) (VCL/AAEM) functionalized with vinylimidazole (VIm) has been prepared in aqueous medium using simple batch dispersion polymerization procedure. Obtained microgel particles are characterized by narrow particle size distribution and their hydrodynamic radius can be varied from 200 to 500 nm (pH = 6, T = 20 °C). The T- and pH-sensitivity of obtained particles can be easily tuned by the variation of the Vim content in the copolymer structure. Increase of VIm content in the microgel structure led to increased swelling of the microgels in acidic medium and strong shift of the volume phase transition temperature to higher temperatures. It has been found that sedimentation behavior of obtained microgels is strongly pH-dependent, and this effect can be used for controlled particle separation.

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.

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

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

Osmotic Compressibility of Soft Colloidal Systems

A turbidimetric analysis of particle interaction of model pH-responsive microgel systems consisting of methacrylic acid-ethyl acrylate cross-linked with diallyl phthalate in colloidal suspensions is described. The structure factor at zero scattering angle, S(0), can be determined with good precision for wavelengths greater than 500 nm, and it measures the dispersion's resistance to particle compression. The structure factor of microgels at various cross-linked densities and ionic strengths falls onto a master curve when plotted against the effective volume fraction, phi(eff) = kc, which clearly suggests that particle interaction potential and osmotic compressibility is a function of effective volume fraction. In addition, the deviation of the structure factor, S(0), of our microgel systems with the structure factor of hard spheres, S(PY)(0), exhibits a maximum at phi(eff) approximately 0.2. Beyond this point the osmotic de-swelling force exceeds the osmotic pressure inside the soft particles resulting in particle shrinkage. Good agreement was obtained when the structural properties of our microgel systems obtained from turbidimetric analysis and rheology measurements were compared. Therefore, a simple turbidimetric analysis of these model pH-responsive microgel systems permits a quantitative evaluation of factors governing particle osmotic compressibility.

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.

Highly pH and Temperature Responsive Microgels Functionalized with Vinylacetic Acid

Temperature-responsive microgels based on poly(N-isopropylacrylamide) (PNIPAM) and functionalized with vinylacetic acid (VAA) are observed to exhibit a host of novel swelling responses compared with equally functionalized microgels prepared using the conventional acrylic acid (AA) and methacrylic acid (MAA) comonomers. VAA−NIPAM microgels are ionized over a narrow pH range and show functional group pKa values which are independent of the degree of ionization. Ionization induces a much larger swelling response in VAA−NIPAM microgels than in the conventional microgels; upon ionization at physiological temperature, VAA−NIPAM swells 3 times more than either AA−NIPAM or MAA−NIPAM. VAA−NIPAM microgels also display sharp, PNIPAM-like thermal deswelling profiles when protonated but, upon ionization, undergo no volume phase transition up to at least 70 °C. The highly responsive and tunable ionization and swelling profiles observed for VAA−NIPAM are consistent with the tendency of VAA to behave as a chain transfer agent, resulting in the incorporation of a large number of well-separated VAA units on highly mobile chain ends at or near the microgel surface. VAA−NIPAM microgels may thus be ideal for use in biomolecule separation, medical diagnostics, and biodelivery applications in which sharp responses to multiple environmental stimuli are required.

Electrical control of reversible microgel flocculation and its estimated performance as a display device

Reversible flocculation of pH-responsive microgels with poly-L-lysine was electrically controlled by a pH modulator. The pH modulator was composed of a polypyrrole-coated Pt electrode coupled with an Ag/AgCl counter-electrode. The applicability of the flocculation system for display devices was examined to determine whether its performance was comparable with that of conventional display devices. A display performance of contrast 50 in 50 ms with operating potentials of ±0.4 V will be attained in a proposed cell where vertical microelectrode arrays are built in.