Bulk Gel Research Articles

Lipid-Based Liquid Crystals As Carriers for Antimicrobial Peptides: Phase Behavior and Antimicrobial Effect.

The number of antibiotic-resistant bacteria is increasing worldwide, and the demand for novel antimicrobials is constantly growing. Antimicrobial peptides (AMPs) could be an important part of future treatment strategies of various bacterial infection diseases. However, AMPs have relatively low stability, because of proteolytic and chemical degradation. As a consequence, carrier systems protecting the AMPs are greatly needed, to achieve efficient treatments. In addition, the carrier system also must administrate the peptide in a controlled manner to match the therapeutic dose window. In this work, lyotropic liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers for AMPs. These LC structures have the capability of solubilizing both hydrophilic and hydrophobic substances, as well as being biocompatible and biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes and hexosomes) have been studied. Three AMPs have been investigated with respect to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060, and LL-37. Characterization of the LC structures was performed using small-angle X-ray scattering (SAXS), dynamic light scattering, ζ-potential, and cryogenic transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra performance liquid chromatography. The antimicrobial effect of the LCNPs was investigated in vitro using minimum inhibitory concentration (MIC) and time-kill assay. The most hydrophobic peptide (AP114) was shown to induce an increase in negative curvature of the cubic LC system. The most polar peptide (DPK-060) induced a decrease in negative curvature while LL-37 did not change the LC phase at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover, cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial activity, whereas particles loaded with peptide LL-37 displayed a loss in its broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction in antimicrobial activity.

Colloidal dispersion gels based on sulfonated polyacrylamide and chromium triacetate for harsh-environment

The aim of this study was to outline the preparation of colloidal dispersion gels (CDGs) based on sulfonated polyacrylamide (SPA) and chromium triacetate and investigating their stability in harsh conditions. The effect of crosslinker, polymer concentration, salinity, and gelation time and temperature on the formation, rheological behavior and size distribution of CDGs and also their thermo-chemical stabilities were investigated. It was found that the shear viscosity and size of CDGs decreased with increasing of preparation time. Dynamic light scattering and scanning electron microscopy evaluations showed that the size of CDGs particles decreased with increasing of the Cr3+ concentration. In addition, SPA solution had yield stress, while CDGs did not. The elevation of temperature inhibits while the salinity does not disturb the formation of CDGs. In the systems with lower polymer concentration, CDGs were formed. Conversely, in the systems with higher polymer concentration, bulk gels were formed. After aging, CDG sample had a minimal viscosity loss, indicating its exceptional thermo-chemical stability.

Interface versus bulk gelation and UCST in hydrophobically assembled TX-100 molecular gels

Abstract Herein, we report on a supramolecular TX-100-based molecular gel, which self assembles largely due to hydrophobic interactions, and we clearly distinguish between surface versus bulk gelation mechanism. The phase diagram of these salt-free solutions, and their gels were characterized by dynamic light scattering (DLS), viscometry, rheology, and surface tension methods to map their microstructure, and thermo-viscoelastic properties. We demonstrate the spontaneous evolution of several hierarchical, but self-assembled soft matter phases starting from a homogeneous aqueous solution as it was gradually cooled from 60 °C to room temperature (20 °C). The Cole-Cole plot profile (loss versus storage modulus plot) indicated that this suspension produced the following three phases: (i) for [TX-100] 60% (v/v), heterogeneous melt. The system exhibited a clear UCST separating the sol and gel domains, and the proposed phase diagram embodied all the observed phases. The gelation time, and the free-energy of gelation were determined from surface tension, and viscosity measurements, they revealed that the self-assembly, and network formation at the air-liquid interface occurred at least 200 s later than the bulk, a behaviour that was anomalous. The gelation phenomenon was discussed through homogeneous nucleation and growth model where the interfacial surface and volume free-energy governed the gelation kinetics. The gel state was dominated by structured water (characterized by Raman band at 3200 cm−1), whereas both in the solution, and in the melt phase there was propensity of partially structured water. It was concluded that aqueous TX-100 dispersions can yield a variety of soft matter phases rich in hierarchy, and dynamics, much of which is not probed hitherto.

Thermoresponsive Wrinkles on Hydrogels for Soft Actuators

Thermoresponsive Wrinkles on Hydrogels for Soft Actuators

Interplay between flow and diffusion in capillary alginate hydrogels.

Alginate gels with naturally occurring macroscopic capillaries have been used as a model system to study the interplay between laminar flow and diffusion of nanometer-sized solutes in real time. Calcium alginate gels that contain homogeneously distributed parallel-aligned capillary structures were formed by external addition of crosslinking ions to an alginate sol. The effects of different flow rates (0, 1, 10, 50 and 100 μl min(-1)) and three different probes (fluorescein, 10 kDa and 500 kDa fluorescein isothiocyanate-dextran) on the diffusion rates of the solutes across the capillary wall and in the bulk gel in between the capillaries were investigated using confocal laser scanning microscopy. The flow in the capillaries was produced using a syringe pump that was connected to the capillaries via a tube. Transmission electron microscopy revealed an open aggregated structure close to the capillary wall, followed by an aligned network layer and the isotropic network of the bulk gel. The most pronounced effect was observed for the 1 nm-diameter fluorescein probe, for which an increase in flow rate increased the mobility of the probe in the gel. Fluorescence recovery after photobleaching confirmed increased mobility close to the channel, with increasing flow rate. Mobility maps derived using raster image correlation spectroscopy showed that the layer with the lowest mobility corresponded to the anisotropic layer of ordered network chains. The combination of microscopy techniques used in the present study elucidates the flow and diffusion behaviors visually, qualitatively and quantitatively, and represents a promising tool for future studies of mass transport in non-equilibrium systems.

Supramolecular metallogels with bulk self-healing properties prepared by in situ metal complexation.

In this feature article, we discuss a series of contributions dealing with the in situ fabrication of supramolecular metallogels (i.e. using low molecular weight ligands and metal ions) that show self-healing properties of the bulk gel phase after complete physical segregation. Most of the advances in this area have taken place during the last three years and are mainly represented by organogels, whereas examples of hydrogels and organic-aqueous gels are still a minority. In situ gelation via metal-coordination of low molecular weight compounds is conceptually different from the use of premade (e.g. in solution) coordination polymers and polymeric structures as gelators and ligands, respectively. In the case of in situ gelation, the cooperative effects of all components of the mixture (i.e. ligand, metal ion, counterions and solvent molecules) in an appropriate ratio under well-defined experimental conditions play a crucial role in the gelation phenomenon and self-healing properties of the material.

Rheology of emulsion-filled alginate microgel suspensions

Emulsion filled polysaccharide gels can be used as carrier systems of lipophilic bioactives in the food, pharmaceutical and cosmetics industry. This carrier system can exist either as bulk or discrete gel systems. In this study the rheological properties of discrete emulsion filled alginate microgel suspension was examined as a function of volume fraction (ϕ) and oil content. Fine emulsion (220nm) was encapsulated within alginate microgels (mean size 36.2–57.8μm) by using the impinging aerosol technique. The microgels (containing 0–77% w/w oil total solids basis) produced were estimated to have particle modulus in the range of 150–212Pa. An increase in oil content in the microgels led to more deformable microgels due to the reduction in gel density. The deformability of microgels influenced the bulk modulus and apparent viscosity of the concentrated suspension. At the same suspension volume fraction (ϕ), suspensions with more deformable microgels exhibited a lower bulk modulus. We also showed that the Carreau and Cross models were adequate in predicting the flow behaviour of the concentrated emulsion filled microgel suspension.

Comparative studies on glycerol monooleate- and phytantriol-based cubosomes containing oridonin in vitro and in vivo

To improve the solubility and bioavailability of oridonin (ORI), glycerol monooleate lipid (GMO)- or phytantriol (PYT)–Poloxamer 407–propylene glycol–water systems were firstly used to develop cubosomes containing ORI for oral delivery. These cubosomes prepared through the fragmentation of bulk gels under homogenization conditions of 1200 bar and nine cycles had a mean particle size of around 200 nm with narrow size distribution, and ORI encapsulation efficiency over 85%. Powder X-ray diffraction and differential scanning calorimetry indicated that ORI was in an amorphous or molecular form in the cubosomes. The internal structures of GMO- and PYT-based cubosomes were revealed by small-angle X-ray scattering as a bi-continuous cubic liquid crystalline phase with Im3m and Pn3m geometry, respectively. About 80% of ORI was released in vitro from GMO- and PYT-based cubosomes at 24 h, showing a sustained release kinetics fitted with Higuchi’s equation. The pharmacokinetic study in rats showed that the PYT-based cubosomes significantly enhanced the adsorption of ORI as compared to the GMO-based cubosomes and ORI suspension, with evidence of longer half-life and greater relative bioavailability (p < 0.01). Therefore, the PYT-based cubosomes containing ORI might be proposed as a promising candidate carrier for the efficient delivery of drug with therapeutic treatment.

Long‐Lived Foams Stabilized by a Hydrophobic Dipeptide Hydrogel

A hydrogel of hydrophobic dipeptides can be used to create a wet foam with long‐term stability. The dipeptide molecules self‐assemble into fiber‐like networks (due to the presence of metal ions) both at air–water interfaces and in the continuous phase. The former creates an interfacial film stabilizing the air bubbles while the latter forms a bulk gel, which prevents bubble movement and retards growth. If the storage modulus (G′) of the bulk hydrogel is sufficiently high it can stop the coarsening of the air bubbles and thus dramatically improve the stability of the foam. Cryogenic scanning electron microscopy and Raman spectra reveals the width of the fibers (200 nm) and that they are held together by hydrogen bonds. In the absence of bubbles, phase separation is observed between a hydrogel and a water‐rich phase; in the foam this can be suppressed provided that the concentration of dipeptides and metal ions are sufficiently high. It is speculated that the resistance of the bubble arrangement to compaction and hence further drainage arrests the process of phase separation. This foam system has the advantages of long stability, low cost, as well as easy preparation; therefore, it has potential applications in food manufacturing, drug delivery, and personal care industries.

Aminoglutethimide-imprinted xerogels in bulk and spherical formats, based on a multifunctional organo-alkoxysilane precursor

The multifunctional alkoxysilane precursor, 2,6-bis(propyl-trimethoxysilylurelene)pyridine (DPS) was designed and synthesized, envisaging a multiple hydrogen-bond interaction in the molecular imprinting of the drug aminoglutethimide (AGT). Imprinted xerogels were obtained in bulk and spherical formats. The spherical format was achieved by pore-filling onto spherical mesoporous silica, as a straightforward technique to generate the spherical format. The bulk gels presented better selectivity for the template against its glutarimide (GLU) analogue (selectivity factor: bulk 13.4; spherical 4.6), and good capacity (bulk 5521μmol/L; spherical 2679μmol/L) and imprinting factor parameters (bulk 11.3; spherical 1.4). On the other hand, the microspherical format exhibited better dynamic properties associated to chromatographic efficiency (theoretical plates: bulk 6.8; spherical 75) and mass transfer, due mainly to the existence of a mesoporous network, lacking in the bulk material. The performance of the imprinted xerogels was not as remarkable as that of their acrylic counterparts, previously described. Overall it was demonstrated that the use of designed new “breeds” of organo-alkoxysilanes may be a strategy to achieve satisfactory imprints by the sol–gel processes. DPS may in principle be applied even more effectively to other templates bearing better-matching spatially compatible acceptor–donor–acceptor arrays.

Experimental study and application of gels formed by nonionic polyacrylamide and phenolic resin for in-depth profile control

Abstract A phenolic resin cross-linked nonionic polyacrylamide (NPAM) gel used for in-depth profile control was systematically analyzed. Long gelation time and strong gel strength of the gel system was obtained by adjusting NPAM or cross-linker concentration. An increase in temperature and salt concentration accelerated the gelation process and improved the gel strength. Although shearing brings a negative effect on gel performance, the gel system still had strong gel strength which could make it long-term stability in in-depth formation. Differential scanning calorimetry determined that this gel system should be used for oilfield application at temperatures below 143 °C. A compact three-dimensional network structure was formed in the bulk gel system and in porous media which contributed to long-term gel stability in the formation. Sand-pack flow experiments showed that the NPAM gel had a good plugging capacity and could selectively plug high permeability zones. By retention, adsorption, and bridging across the pore throats, the gel systems effectively reduced the permeability of porous media in high permeability zones and diverted fluid into low permeability zones, and thus improved the formation profile. Furthermore, this gel system for in-depth profile control treatment was successfully used in the Xinjiang oilfield of China which provided a reference for other similar high water cut oilfields for water control worldwide.

Revisited: DGT speciation analysis of metal–humic acid complexes

Environmental context Humic acids and their metal complexes may be sorbed by the gel used in diffusive gradients in thin films (DGT) speciation analysis. Owing to the low mobility of the humic entities, the sorption process is very slow. As a consequence, the delay times involved in establishing a steady-state metal diffusion flux may be in the order of days. Abstract Soil humic acids and their metal complexes are sorbed by hydrogel phases such as those used in DGT analysis. The accumulation is spatially inhomogeneous: a thin film near the interface with the aqueous medium typically hosts ~10 times the concentration in the medium, whereas the bulk gel features an accumulation factor of ~2. Here we discuss the consequences of these sorption properties for the usual type of DGT experiment. It appears that the eventual steady-state metal flux is not affected, but the characteristic time of establishing truly steady-state diffusion conditions may be even longer than the common DGT deployment time of a few days.

Abstract 1997: Label-free concentration of viable breast cancer CTCs for single cell Western blotting

Abstract The isolation of circulating tumor cells (CTCs) in blood can aid in cancer prognosis, characterize genetic mutations for targeted therapies, and elucidate the biological mechanisms of metastasis. While CTCs provide clinical utility, there are still several technical difficulties with CTC isolation and analysis. CTCs are very rare (1-10 cells/mL of blood) and current isolation methods rely on immunocapture, require long sample preparation, and fail to deliver viable cells. Further, recent advances in single cell analysis of CTCs have been limited to genomic studies, in which DNA/mRNA does not provide a complete picture of CTCs at the functional level, as mRNA expression may only account for a portion of protein expression. The ability to study and measure the protein expression of CTCs could provide insight into the mechanisms driving cancer progression and signaling dysregulation. Unfortunately, conventional proteomic tools (e.g. immunocytochemistry and Western blot) either do not provide sufficient specificity or sensitivity toward single cell levels. Thus, there is a lack of tools that can provide quantitative protein analysis for rare CTCs. To address this gap, we enable rare cell Western blotting by combining isolation and proteomic technologies in a unique workflow: (i) Label-free Vortex enrichment of rare larger cells from blood samples. Larger cancer cells are trapped within an array of microscale fluid vortices that form in simple rectangular reservoirs, while smaller blood cells pass through. The cancer cells are stably maintained in the vortices, allowing for solution exchange, followed by release upon lowering the flow rate. With this device, we were able to release a small volume (∼500 μL) of concentrated, viable cancer cells (MCF7) from healthy blood, at high throughput, capture efficiency (35%), purity (&amp;gt;80%), and ∼10,000 fold enrichment. CTCs were also successfully extracted and enumerated from the blood of patients with breast cancer (N = 18, from 0.75 to 23.25 CTCs/mL). (ii) High-specificity and multiplexed protein analysis of rare cancer cells with single cell Western blotting (scWB). Enriched CTCs are placed into microwells patterned into a polyacrylamide gel for the scWB assay (in-situ chemical lysis in the microwells, electrophoresis into bulk gel layer, photo-immobilization, and subsequent antibody-probing of immobilized proteins). Here, we demonstrate scWB compatibility with rare cells by spiking MCF7s into normal blood and performing protein separations. The scWB is multiplex and can assay several target proteins simultaneously. Cells stained for surface markers (anti-EpCAM) are also compatible, and the scWB can resolve complete immunocomplexes without disrupting the location of the intracellular targets (GAPDH, ERK). With the integration of these technologies, we push the limits of quantitative protein analysis of CTCs, an essential step to better understand these rare populations. Citation Format: Elly Sinkala, Elodie Sollier, Corinne Renier, James Che, Stefanie S. Jeffrey, Amy E. Herr. Label-free concentration of viable breast cancer CTCs for single cell Western blotting. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1997. doi:10.1158/1538-7445.AM2015-1997

Ionic liquid hydrogel templates: Bulkgel, cryogel, and microgel to be used for metal nanoparticle preparation and catalysis

Here, we report the preparation of various crosslinked polymeric matrices from 3-acrylamidopropyl)-trimethylammonium chloride as p(APTMACl) ionic liquid hydrogels in the forms of bulk gel, cryogel, and microgel. Their utilization for in situ metal nanoparticle synthesis of Co and Ni, and then the comparison of catalytic performances of these materials in the reduction of 4-nitrophenol (4-NP), 4-nitroaniline (4-NA), and 4-nitrobenzaldehyde (4-NBA) to the corresponding amine forms of 4-AP, 4-AA, and 4-ABA, respectively, are investigated. As the polymeric hydrogel matrices are inherently positively charged, the metal salts of CoCl2 and NiCl2 were loaded into hydrogel matrices from the corresponding metal salt solution in ethanol. It was found that morphology and sizes of p(APTMACl) ionic liquid hydrogel materials played a great role in catalytic performances for the nitro compounds. The effect of temperature and kinetic parameters of different polymeric matrices for the reduction of 4-NP to 4-AP was investigated. The activation energies for bulk gel, cryogel, and microgel were calculated as 44.74, 34.02, and 40.7kJmol−1, respectively.

Comparison of Gelation Behavior and Morphology of Resorcinol–Hexamethylenetetramine–HPAM Gel in Bulk and Porous Media

Polymer gel treatment is a proven cost-effective method to control excessive water production and improve sweep efficiency in many mature oilfields; however, it is worth noting that there exist differences between gelation behavior and morphology in bulk and porous media, which are directly related to the success of a gel treatment. In this study, the gelation behavior and morphology of resorcinol–hexamethylenetetramine–HPAM gel in bulk and porous media were studied. Results revealed that the differences between the gelation time and morphology in bulk and porous media were obvious. The relationship between bulk gelation time and static gelation time in porous media was correlated. Dynamic gelation behavior in porous media confirmed that the gelation could occur during flow in porous media and the gelation location can be inferred to determine gel placement. This study could provide the basis for determining well shutoff time and understanding the blocking mechanism in porous media.

Characteristics of the bulk hydrogels made of the citric acid cross-linked whey protein microgels

A non-toxic, biocompatible and generally recognized as safe (GRAS) chemical, citric acid, was employed for pH adjustment and cross-linking of whey proteins either before or after their microgelification by heat. A conventionally-made microgel sample was also fabricated by using hydrochloric acid for pH adjustment on 5.8 and subsequent heating at 85 °C. Size approximation of microgel particles from atomic force microscopy images indicated that chemical cross-linking resulted in smaller particles (80–130 nm and 100–150 nm for post- and pre-microgelification cross-linked samples, respectively) compared with conventional counterpart (150–300 nm). Based on Fourier transform infrared spectroscopy results, it was concluded that prolonged citric acid cross-linking of whey proteins prior to microgelification caused extensive cross-linking of protein units and preserved proteins α-helical structure. The pre-cross-linked microgels formed firmer (higher fracture stress and complex modulus) calcium-induced cold-set bulk gel with higher water-holding capacity and denser microstructure compared with conventional and post-cross-linked microgels. These superiorities were attributed to existence of higher number of carboxyl residues in the structure of the pre-cross-linked microgels. The alteration in the properties of the final bulk hydrogels via cross-linking of the microgel building-units can be exploited for modulating and controlling the release behavior of loaded cargo within hydrogel, resulting in a more tuned application of gels as edible delivery systems.

Sol-gel encapsulation of biomolecules and cells for medicinal applications.

The sol-gel process provides a robust and versatile technology for the immobilization of biologicals. A wide range of inorganic, composites and hybrid materials can be prepared to encapsulate molecular drugs, proteins, antibodies/antigens, enzymes, nucleic acids, prokaryotic and eukaryotic cells into bulk gels, particles and films. This review describes the applications of sol-gel encapsulation relevant to medicinal chemistry focusing on the recent development of biosensors as well as systems for production, screening and delivery of bioactive compounds and biomaterials.

EXPERIMENTAL STUDY ON FOAMED GEL FLOW IN POROUS MEDIA

Foamed gel has the advantages of aqueous foam and bulk gel, widely used in profile modification for oil recovery. Distribution characteristics of the foamed gel in porous media was observed by microscope. With gelling time increasing, bubbles coalescence occurs, and the average diameter of the foamed gel gradually becomes larger. During the subsequent water flooding process, bubble diameter decreases. Through single-core displacement experiments, the several effects on the blocking capability of foamed gel were studied. Blocking capability first increases and then decreases with foam quality, and the best foam quality is 50% in the experiments. Blocking capability first increases obviously with permeability, and then remains almost stable. Although the residual resistance factor decreases with oil saturation, foamed gel has good tolerance with crude oil compared with aqueous foam. Forward injection for subsequent water flooding is better than reverse injection. In a thorough comparison of aqueous foam, gel, polymer, and foamed gel, the blocking capability of foamed gel is the greatest. Cross-linked gel increases the strength of bubble film, and prolongs the blocking duration time. Through dual-core displacement experiments, the effects of permeability ratio and injection rate on profile modification were studied. Along with the increasing of permeability ratio, the foamed gel profile modification effect first increases, and then decreases. When permeability ratio is 7.0, profile modification effect is the best. Profile modification effect decreases with injection rate. The improved oil recovery efficiency for immature foamed gel and subsequent water flooding is 31.3% for parallel sandpack, with permeability ratio of 6.8. Foamed gel has real potential for profile modification in the oil field.

Gel-assisted synthesis of oleate-modified Fe3O4@Ag composite microspheres as magnetic SERS probe for thiram detection

Fast detection and identification of thiram, a kind of well-known pesticide, presents a great challenge to environmental researchers. This work developed a kind of oleate-modified Fe3O4@Ag core@shell composite microsphere as a magnetic separable SERS substrate for quick selective sensing of thiram. In the synthesis procedure, the bulk gel containing oleate was used as the reaction system, which not only avoided the aggregation of Fe3O4 microspheres by fixing them during silver coating, but also modified the silver shell with oleate groups simultaneously. Through serial experiments, the silver seeds on the surface of the Fe3O4 microspheres were found to influence the shell growth strongly, and the Fe3O4@Ag core@shell composite microspheres could only be obtained when the Fe3O4 microspheres with dense silver seeds were used as the template. The surface capped oleate groups and the inner magnetic core made the as-obtained Fe3O4@Ag core shell composite microsphere a highly efficient SERS substrate for fast and selective monitoring of thiram in solution, and the well-coated Fe3O4@Ag core@shell composite microspheres exhibited excellent selective probing performance for thiram with a detection limit as low as 10−8 M.

Photodimerisation of a coumarin-dipeptide gelator.

Here we report a coumarin based hydrogelator that can form bulk gels, or homogeneous thin gels via an electrochemical pH drop. The gel can then be strengthened by post-gelation photodimerisation of the coumarin groups by irradiating with UV light.