Microgels Research Articles

Using intra-microgel crosslinking to control the mechanical properties of doubly crosslinked microgels.

Microgels (MGs) are crosslinked polymer particles that swell when the pH approaches the pKa of the constituent polymer. Our earlier work showed that concentrated MG dispersions can be covalently interlinked to form macroscopic hydrogels, which are termed doubly crosslinked microgels (DX MGs). Here, we study for the first time the effects of intra-MG crosslinking on the swelling of the MGs and the mechanical properties of the DX MGs. The MGs were synthesised by emulsion copolymerisation of ethyl acrylate (EA) or methacrylic acid (MAA) and divinylbenzene (DVB). The latter was a crosslinking monomer. For comparison, MGs were prepared where DVB was replaced by either 1,4-butanediol diacrylate (BDDA) or a 1 : 1 mixture of both DVB and BDDA. The MG swelling behaviours were studied by dynamic light scattering; whereas, the DX MG mechanical properties were studied by dynamic rheology and uniaxial compression measurements. Inclusion of DVB within the MGs resulted in both highly swelling MGs and highly ductile DX MGs. The average strain-at-break value for the DVB-containing DX MGs was 76% which represents the highest value yet reported for a DX MG prepared using commercially available monomers. It was also shown that good tuneability of the DX MG properties could be obtained simply by controlling the DVB and BDDA contents within the MG particles. Analysis of the swelling and compression data enabled relationships between the volume-swelling ratio of the MGs and either the modulus or strain-at-break values for the DX MGs. These relationships also applied to a DVB-free system prepared with a low BDDA content. An interesting conclusion from this study is that the DX MGs can be thought of mechanically as macroscopic MG particles. The results of this study provide design tools for improving DX MG ductility and hence increasing the range of potential applications for this new class of hydrogel.

Recombinant 1F9 spidroin microgels for murine full-thickness wound repairing.

The study of the stimulating effect of the microgels (MGs) based on recombinant 1F9 spidroin on the regeneration of the deep skin wound in mice was carried out. The use of spidroin MGs was shown to increase significantly the quality of healing compared to the control. The introduction of the MG in the wound edges led to recovery of all the structural elements of the skin: the epidermis, the dermis, including vascular and nervous network, in the periphery of the wound underlying muscles, and skin appendages (sebaceous and sweat glands and hair follicles) was revealed.

Mixtures of pH-responsive microgels and temperature-responsive star-like copolymers; from heteroaggregation to gelation

Heteroaggregation of dispersions has attracted much interest in the literature, especially when one or more components are stimulus responsive. Here, we study binary mixtures of microgels (MG) and star-like copolymers for the first time. The study investigated the use of complementary hydrogen bonding between carboxylic acid and amide groups to construct heteroaggregates and gels that contained temperature- and pH-responsive components. The pH-responsive MG contained methacrylic-acid and had an apparent pKa of 8.2. Two new star-like copolymers were introduced which comprised a cationic backbone with poly(N-isopropylacrylamide) side-chains. They are abbreviated as M1–PNP. A combination of complementary hydrogen bonding and hydrophobic interactions was shown to cause formation of heteroaggregates for mixed MG/M1–PNP dispersions at room temperature and at pH values less than the MG pKa. MG/M1–PNP heteroaggregate formation occurred over a wide pH-range and also in the presence of 0.2 M NaNO3. The heteroaggregates exhibited temperature-dependent hydrodynamic diameters and zeta potentials. Concentrated MG/M1–PNP dispersions formed self-supporting hybrid gels at 45 °C and gel formation also occurred over a wide pH range. The gels contained 80% MG with respect to total polymer content and were remarkably ductile. They had yield strains greater than or equal to 290%. There was evidence that the elasticity and ductility of the hybrid gels were controlled by the MG and M1–PNP components, respectively. The new M1–PNP star-like copolymers introduced here had superior temperature-triggered gel-formation properties compared to related copolymers and should be a versatile system for conferring temperature-responsive gelation properties to polymer colloids containing carboxylic acid groups.

Temperature-sensitive molecularly imprinted microgels with esterase activity

Temperature-sensitive molecularly imprinted microgels (MIGs) exhibiting esterase activity were prepared by a reverse emulsion method using dialdehyde dextran-histidine conjugate (PAD-His) as the functional macromonomer and p -nitrophenyl phosphate (NPP) as the stable transition state analogue (TSA) as well as Co2+ as the coordination center. The catalytic activity of MIGs was greatly influenced by the template amount, and could be modulated by temperature. The hydrolysis kinetics of p -nitrophenyl acetate (NPA) in the presence of MIGs could be described by the Michaelis-Menten equation. The Michaelis-Menten constant and maximium velocity were found to be 2.2×10-5 mol/L and 2.04×10-8 mol/h, respectively. In addition, the MIGs were found to have a high catalytic selectivity to NPA.

Temperature-sensitive molecularly imprinted microgels with esterase activity

Temperature-sensitive molecularly imprinted microgels (MIGs) exhibiting esterase activity were prepared by a reverse emulsion method using dialdehyde dextran-histidine conjugate (PAD-His) as the functional macromonomer and p-nitrophenyl phosphate (NPP) as the stable transition state analogue (TSA) as well as Co2+ as the coordination center. The catalytic activity of MIGs was greatly influenced by the amount of the template, and could be modulated by temperature. The hydrolysis kinetics of p-nitrophenyl acetate (NPA) in the presence of MIGs could be described by the Michaelis-Menten equation. The Michaelis-Menten constant and maximum velocity were found to be 2.2 × 10−5 mol/L and 2.04 × 10∞8 mol/h, respectively. In addition, the MIGs were found to have a high catalytic selectivity to NPA.

Controlling Gold Nanoparticle Stability with Triggerable Microgels

The interaction of a photodegradable surfactant (PS, 4-hexylphenylazosulfonate, C(6)PAS) with microgels (MGs) of poly(2-vinyl pyridine) (MGA) in the protonated state (pH 3) has been investigated. Electrophoretic mobility measurements confirm that negatively charged PS interacts with positively charged MGA to form mixed PS-MG complexes. This was sensed by a decrease in the effective PS-MGA charge and a switch in sign of electrophoretic mobility, from positive to negative, with increasing PS concentration. After the addition of extra positive microgels (MGB), the system undergoes coflocculation. Incident UV irradiation was used to photolyze the anionic PS, effectively eliminating the headgroups, thereby lowering the electrostatic interactions between PS and MGA microgel networks. Consequently, a reversal of MGA charge occurred, leading to electrostatic repulsions and causing the MGs to reswell and redisperse, with both MGA and MGB now being positively charged and hence stabilized against coflocculation. Extending this approach, negatively charged gold nanoparticles (AuMES) have been incorporated into the PS-MGA complexes. Atomic absorption spectroscopy (AAS) showed that 100% of the AuMES particles were recovered after coflocculation of (PS-MGA)-AuMES complexes with MGB. Furthermore, approximately 75% of the AuMES could be redispersed after UV irradiation to restabilize the dispersion. This system provides an interesting method for phase separation and gold nanoparticle recovery for reuse and recycling.

Formulation and characterization of tramadol-loaded IPN microgels of alginate and gelatin: Optimization using response surface methodology

Tramadol-loaded interpenetrating polymer network (IPN) alginate-gelatin (AG) microgels (MG) were prepared by the chemical cross-linking technique with glutaraldehyde as cross-linking agent and were optimized using response surfaces. A central composite design for 2 factors, at 3 levels each, was employed to evaluate the effect of critical formulation variables, namely the amount of gelatin (X1) and glutaraldehyde (X2), on geometric mean diameter, encapsulation efficiency, diffusion coefficient (D), amount of mucin adsorbed per unit mass (Qe) and 50 % drug release time (t50). Microgels with average particle size in the range of 44.31-102.41 μm were obtained. Drug encapsulation up to 86.5 % was achieved. MGs were characterized by FT-IR spectroscopy to assess formation of the IPN structure and differential scanning calorimetry (DSC) was performed to understand the nature of drug dispersion after encapsulation into IPN microgels. Both equilibrium and dynamic swelling studies were performed in pH 7.4 phosphate buffer. Diffusion coefficients and exponents for water transport were determined using an empirical equation. The mucoadhesive properties of MGs were evaluated in aqueous solution by measuring the mucin adsorbed on MGs. Adsorption isotherms were constructed and fitted with Freundlich and Langmuir equations. In vitro release studies indicated the dependence of drug release on the extent of cross-linking and the amount of gelatin used in preparing IPNs. The release rates were fitted to a power law equation and Higuchi's model to compute the various drug transport parameters, n value ranged from 0.4055 to 0.5754, suggesting that release may vary from Fickian to quasi-Fickian depending upon variation in the formulation composition.

Recovery of gold nanoparticles using pH-sensitive microgels

A simple method to disperse and recover gold nanoparticles (AuNPs) based on pH-induced heteroaggregation of mixed positive/negative aqueous microgels (MGs) is described. Interestingly, stability of these composite inorganic–organic systems can be readily and reversibly controlled by using pH, affording flocculated (pH 3) or re-dispersed (pH 10) Au-NPs as desired. Atomic absorption spectroscopy shows that an efficient and effective recovery of the AuNPs can be achieved. These systems provide novel triggerable and recyclable alternatives to classical recovery methods.

Detection of DNA using bioactive paper strips

Paper strips containing DNA-conjugated microgels (MG) are used to achieve sensitive DNA detection in three steps: target DNA promoted ligation of a DNA primer to the MG-bound DNA, rolling circle amplification (RCA) between the primer and a circle DNA, and hybridization of the RCA products and a fluorescent DNA probe.

PMMA‐based microgels for controlled release of an anticancer drug

AbstractMethyl methacrylate (MMA), methoxy poly(ethylene glycol) monomaleate (MPEG), and acrylamidoglycolic acid (AGA) terpolymeric microgels (MGs) have been synthesized by free‐radical surfactant‐free emulsion polymerization. MPEG was synthesized from maleic anhydride and methoxy poly(ethylene glycol). The MGs were crosslinked with ethylene glycol dimethacrylate, and the chemical crosslinking was confirmed by Fourier transform infrared spectroscopy. 5‐Fluorouracil (5‐FU), a model anticancer drug, has been loaded into the MGs by in situ and adsorption methods. Empty as well as drug‐loaded MGs were then characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and X‐ray diffraction (XRD). DSC and XRD studies indicated a molecular level dispersion of the drug in PMMA MGs during in situ loading. TEM images showed the formation of spherical MGs. In vitro release of 5‐FU from the crosslinked poly(MMA‐co‐AGA‐co‐MPEG) MGs were investigated at both pH 7.4 and 1.2 buffer medium that controlled release of the drug up to ∼ 18 h. Both the encapsulation efficiency and the release patterns were dependent on the amount of crosslinking agent and the amount of drug loaded. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Novel chitosan-based pH-sensitive interpenetrating network microgels for the controlled release of cefadroxil

This paper addresses development of novel pH-sensitive interpenetrating polymeric network (IPN) microgels (MGs) based on chitosan, acrylamide- grafted-poly(vinyl alcohol) and hydrolyzed acrylamide- grafted-poly(vinyl alcohol) that are crosslinked with glutaraldehyde and used in the controlled release (CR) of cefadroxil, an antibiotic drug. The MGs formed were characterized by Fourier transform infrared spectroscopy to confirm the grafting and crosslinking reaction, scanning electron microscopy to understand the surface morphology and differential scanning calorimetry to conform a uniform distribution of the drug in the polymer matrix. Swelling experiments on hydrogels provided important information on drug diffusion properties. In vitro release results performed in acidic and basic media affected the drug release characteristics. Release data have been analyzed using an empirical equation to understand about the transport of drug containing solution through the polymeric matrices. Extent of crosslinking was studied in terms of size of MGs as well as their release characteristics. Effect of drug loading on encapsulation efficiency was investigated to find a linear manner. IPN matrices of this study were able to extend the release rates from conventional dosage release times to more than 10 h.

PH sensitive interpenetrating network microgels of sodium alginate‐acrylic acid for the controlled release of ibuprofen

AbstractpH‐Sensitive interpenetrating network (IPN) microgels (MGs) of sodium alginate (NaAlg) and acrylic acid have been prepared by using water‐in‐oil (W/O) emulsion technique. The MGs were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X‐ray diffractometer (X‐RD). The release of ibuprofen (IB), an anti‐inflammatory drug, from these MGs was studied in pH 1.2 and 7.4 media. MG network consists of NaAlg, which disintegrates in the intestinal fluid, while poly(acrylic acid) provides pH‐sensitivity to the microgel network. The system developed in this study showed a pH‐sensitivity for the release of IB, which was attributed to the diffusion controlled release of the drug through the surfaces of MGs that undergo disintegration after swelling, depending upon the chemical composition of MGs and pH of the medium. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006