Gel Disks Research Articles

Anomalous release of indoles from amorphous solid dispersion formed with a polymeric network

AbstractAmorphous solid dispersion (ASDs) is a technique used in the pharmaceutical industry to enhance the solubility, dissolution rate, and bioavailability of poorly soluble drugs. Polymeric materials, and recently polymer gels form and stabilize the amorphous structure by inhibiting the aggregation/precipitation of such drugs. In this work indole, 5-aminoindole and 5-hydroxyindole loaded poly (N-isopropylacrylamide) (PNIPA) hydrogels were studied. Swelling and uptake measurements, X-ray diffraction (XRD), liquid and solid phase nuclear magnetic spectroscopy (NMR) and high sensitivity differential scanning calorimetry (DSC) were applied to understand the drug – matrix interactions affecting the release. We confirmed that the hydrogel fostered the fine uniform distribution of the hydrophobic probe molecules and successfully prevented any crystalline or amorphous phase formation during water removal, leading to a glassy solution, a special form of ASD. Despite the limited difference between their chemical composition the probe molecules showed dissimilar drug release behavior from dried loaded gel disks. While Nuclear Overhauser Enhancement Spectroscopy (NOESY) measurements revealed a “bidental” interaction between 5-hydroxiindole and the polymer, no localized interactions were found for indole. The release of the bidentally linked derivatives is rapid and complete: they act as molecular spacers, promoting the rehydration of the chains. In contrast, part of the indole remains irreversibly trapped being confined between the chains without any orientation, shedding light on the role of the steric consequences of the interaction. Our findings also indicate that such drug delivery compositions should be treated as ternary systems (carrier + drug + liquid) already in the design stages of drug release systems.

Large force actuator using an electro-adhesive gel super multi-disk

Actuators with clutch mechanisms have advantages in safety, backdriveability, and controllability for human-coexistence robots. This paper presents a large force actuator using electro-adhesive gels, which are functional materials controlled by the magnitude of an electric field. The developed actuator can generate and continuously control a force over 560 N and resist with a small force when de-energized. The number of electro-adhesive gel disks is drastically increased to increase the generative force. This paper reports the structural plan for the new actuator and experiments to investigate its basic characteristics. Based on the experimental results, an actuator model is identified for the future design of its control system. This paper contributes to the development of a clutch-type linear actuator with a large generative force, maintaining safety and a high force-to-weight ratio. It also addresses the problem of high-voltage power supply costs for electro-rheological and electro-adhesive materials.

Fabrication methods for a gel-based separation-free device for whole blood glucose detection

In this paper, we describe two fabrication methods (well array-based and biopsy punching-based) of gel disks to construct a gel-based point-of-care (POC) diagnosis device for direct colorimetric measurement of human whole blood glucose without any extra blood separation step. The gel disks are made of Polyethylene glycol (PEG) diacrylate (PEG-DA) containing immobilized glucose colorimetric assay reagents. The performances of three types of PEG-DA gel (molecular weight: 575, 3,400, and 10,000) based sensors as well as the two fabrication methods were investigated.•The fabricated devices enabled colorimetric whole blood glucose sensing assay without the need for blood cell separation•The biopsy punching-based gel disk fabrication method provided less variation on the fabricated gel disks

Diffusive gradients in thin films based on banana peel and moringa seeds binding gel disks for in situ measurement of Cd, Cu, Pb and Zn

ABSTRACT Novel Diffusive Gradients in Thin Films (DGT) binding agents, Musa cavendishi banana peel (BP) and Moringa Oleifera seeds (MOS) immobilised in agarose gel, have been developed and validated for the determination of Cd, Cu, Pb and Zn in waters. The agarose-BP and agarose-MOS gel disks were characterised by Scanning Electron Microscopy, Energy Dispersive X-ray Spectrometry and Porosimetry by nitrogen adsorption. Elution of analytes from the binding agents was successfully performed with 2 mol L−1 HCl. The accumulation of Cd, Cu, Pb and Zn in DGT devices based on agarose-BP and agarose-MOS (DGT-BP and DGT-MOS) agreed well with the theoretical curves predicted by the DGT equation in synthetic solutions (500 µg L−1 for each analyte). The uptake of DGT-BP and DGT-MOS for Cd, Cu, Pb and Zn was found to be independent of ionic strength of solutions up to 0.005 mol L−1 and for the entire studied pH range (from 3.5 to 8.0). Validation of DGT-BP and DGT-MOS methods was carried out by deploying the devices in spiked river water (the Corumbataí and the Piracicaba river). The recoveries obtained for the natural water matrices ranged between 40% and 150%. DGT-labile concentrations in situ for DGT-BP and DGT-MOS (performed in acid mine drainage) were also consistent with the values measured by conventional DGT-Chelex, albeit DGT-BP had a better binding capacity in acid drainage water. The predictions performed by chemical speciation modelling vMINTEQ were in general agreement for Pb using DGT-MOS (CDGT-MOS/Cdissolved 50% and Pb+2 MINTEQ species 41.9%) and for Cu using DGT-BP (CDGT-BP/Cdissolved 55% and Cu+2 MINTEQ species 62%). The proposed DGT-BP and DGT-MOS reaffirm the use of residual biomass as binding phase in the DGT technique, featuring low costs in production and ‘green’ technology approaches.

Computational design of shape-programmable gel plates

Polymer gel plates may be programmed to morph into three-dimensional configurations upon swelling. An effective strategy to control such shape transformations consists in patterning the in-plane cross-linking density of the polymer network to realize non-homogeneous swelling. In general, one needs to solve an inverse problem to determine the shear modulus field that produces a given target shape. Here, we propose a computational framework for the solution of such an inverse problem, which we validate against two benchmark problems, i.e. making cones and saddles from gel disks.

Immobilization of β-galactosidase on carrageenan gel via bio-inspired polydopamine coating

In the context of diligent efforts directed to develop new polymeric matrices for enzyme immobilization, we developed carrageenan gel disks activated with bio-inspired polydopamine layer. The carrageenan gel disks were firstly treated with polycationic polymer (hyperbranched polyamidoamine) followed by a polydopamine layer. Such a layer can act as an active platform for the covalent immobilization of enzymes via Michael addition and Schiff base. The mechanical strength of the coated gel disks was obviously enhanced. β-galactosidase was successfully immobilized with a loading efficiency of about 52 %. Furthermore, the immobilized β-galactosidase exhibited enhanced activity at a broader range of pH and temperature. Additionally, the immobilized β-galactosidase preserved around 80 % of the initial activity during the eleven reusability cycles. Generally, activation of the gel disks with the bio-inspired polydopamine layer considered as a safe alternative to the glutaraldehyde due to its cytotoxic. Accordingly, the easily formed carrageenan gel disks coated with polydopamine could have potential as enzyme carrier in drug and food industries.

Green synthesis of cellulose nanofibers using immobilized cellulase

Isolation of cellulose nanofibers (CNF) using cellulase immobilized on cheap and easily formed polymeric gel disks is discussed. Such gel disks based on carrageenan gel coated with hyperbranched polyamidoamine that can covalently bind to cellulase through glutaraldehyde spacer. Thermal and mechanical stability of the coated gel disks were significantly improved. Free and immobilized cellulase exhibited maximum activities at 50 °C and pH 5. However, immobilized cellulase exhibited broader temperature stability than in the free form. Additionally, immobilized cellulase gel disks can be easily separated and reused with great reusability capacity of about 85% of the initial activity after six cycles. Immobilized cellulase was capable to disintegrate cellulose fibers providing nanofibers with diameter of 15–35 nm and several micrometers long. Overall, enhanced thermal stability and reusability of immobilized cellulase pave the way for its use in industrial production of CNF that can be applicable for biomedical and food packaging applications.

Agar-carrageenan hydrogel blend as a carrier for the covalent immobilization of β-D-galactosidase

κ-Carrageenan (Car) was mixed with agar in order to improve the treated gel’s ability to covalently immobilize enzymes. The treatment process of the produced agar-Car gel involved reacting with both polyethyleneimine and glutaraldehyde so as to provide the functional groups necessary for the covalent binding of enzymes. The positive effect imparted by the addition of Car to agar was confirmed through the statistical Plackett-Burman design (PBD). The PBD was employed to investigate the effects of 11 factors on the preparation of the treated agar-Car gel disks, and the immobilization of β-D-galactosidase (β-gal) onto these disks. The PBD provided recommendations on the levels at which 10 of the tested factors should be employed in the future as these factors were shown to be insignificant. On the other hand, the significant factor, the loading enzyme’s activity, was optimized in order to attain the maximum observed activity of immobilized β-gal which amounted to 166.2 U/g gel. It was also shown that the agar-Car immobilized β-gal maintained 97.7% of its initial observed activity during its fifteenth reusability cycle. Open image in new window

Skin Tattoos Alter Sweat Rate and Na+ Concentration.

The purpose of this study was to compare the sweat rate and sweat Na concentration of tattooed versus nontattooed skin. The participants were 10 healthy men (age = 21 ± 1 yr), all with a unilateral tattoo covering a circular area at least 5.2 cm. Sweat was stimulated by iontophoresis using agar gel disks impregnated with 0.5% pilocarpine nitrate. The nontattooed skin was located contralateral to the position of the tattooed skin. The disks used to collect sweat were composed of Tygon® tubing wound into a spiral so that the sweat was pulled into the tubing by capillary action. The sweat rate was determined by weighing the disk before and after sweat collection. The sweat Na concentration was determined by flame photometry. The mean sweat rate from tattooed skin was significantly less than nontattooed skin (0.18 ± 0.15 vs 0.35 ± 0.25 mg·cm·min; P = 0.001). All 10 participants generated less sweat from tattooed skin than nontattooed skin and the effect size was -0.79. The mean sweat Na concentration from tattooed skin was significantly higher than nontattooed skin (69.1 ± 28.9 vs 42.6 ± 15.2 mmol·L; P = 0.02). Nine of 10 participants had higher sweat Na concentration from tattooed skin than nontattooed skin, and the effect size was 1.01. Tattooed skin generated less sweat and a higher Na concentration than nontattooed skin when stimulated by pilocarpine iontophoresis.

A simplified model for equilibrium and transient swelling of thermo-responsive gels.

A simplified model is developed for the elastic response of thermo-responsive gels subjected to swelling under an arbitrary deformation with finite strains. The constitutive equations involve five adjustable parameters that are determined by fitting observations in equilibrium water uptake tests and T-jump transient tests on thin gel disks. Two scenarios for water release under heating are revealed by means of numerical simulation. When the final temperature in a T-jump test is below the volume-phase transition temperature, deswelling is characterized by smooth distribution of water molecules and small tensile stresses. When the final temperature exceeds the critical temperature, a gel disk is split into three regions (central part with a high concentration of water molecules and two domains near the boundaries with low water content) separated by sharp interfaces, whose propagation is accompanied by development of large (comparable with the elastic modulus) tensile stresses.

Biopolymeric formulations for biocatalysis and biomedical applications.

Three gel disks formulations prepared using chitosan (Chito) or polyethylenimine (PEI) followed by glutaraldehyde were prepared for biocatalysis and biomedical applications. The carriers have been used to immobilize lactase covalently and it was evaluated in terms of enzyme loading capacity and enzyme kinetics (km and Vmax). The Km of the Chito formulation was almost half that of the PEI formulations, which is favored in industries. On the other hand, the gel disks were evaluated in terms of their swelling kinetics and the gels' morphology using SEM. The mechanism of the three gels' swelling was also studied and it was found to be non-Fickian, where the mechanism of transport depends on both the diffusion and polymer relaxation, which are controlling the overall rate of water uptake. The Chito formulation was 2–5 folds and PEI formulations were 33–62 folds in terms of the swelling rate constant and the diffusion rate, respectively. These results were highly supported by the SEM. This study will help scientists to design the right polymer network for enzymes immobilization as well as control the surface area and the swelling power of the polymers for different applications such as drug delivery systems and tissue engineering.

Grafted Carrageenan Gel Disks and Beads with Polyethylenimine and Glutaraldehyde for Covalent Immobilization of Penicillin G Acylase

The precursor for production of 65% worldwide antibiotics, 6-aminopenicillanic acid, has been produced using covalently immobilized penicillin G acylase (PGA) onto modified grafted carrageenan gels. Two shapes of gel were prepared, gel disks and gel beads by using the parallel plates and Encapsulator devises, respectively. Different sizes of gel disks and beads were tested to choose the best sizes for both gel types. 2 2 Full-factorial central composite design (CCD) was applied for optimisation of enzyme loading process. The results revealed that maximal enzyme loading of 11.07 and 14.30 U/g of gel disks and beads respectively could be achieved after soaking the gels in an enzyme loading solution of 20 U of PGA for 16 h for both gel types. The generated model was found to be very adequate for PGA immobilization process 91% accuracy was attained for gel disks as the experimental value was 11.07 U/g disk compared to 10.1 U/g disk for the predicted value while 95% accuracy was attained using gel beads as the experimental value was 14.30 U/g beads compared to 14.07 U/g beads for the predicted value. This result is 40% higher than that obtained in our previous work using gel disks. The immobilization of PGA onto gel beads increased the optimum pH from 6 to 6.5–7 while the reaction temperature increased dramatically from 45 � Ct o 75 � C compared to the free enzyme, respectively. Thus, the modified carrageenan-polyethylenimine-glutaraldehyde gel beads could be a good and promising candidate for the industrial use.

Speciation of lead in seawater and river water by using Saccharomyces cerevisiae immobilized in agarose gel as a binding agent in the diffusive gradients in thin films technique

Saccharomyces cerevisiae immobilized in agarose gel is proposed as a binding agent for the diffusive gradients in thin films (DGT) technique for determination of Pb in river water and seawater. DGT samplers were assembled with the proposed binding agent (25-mm disk containing 20%, m/v, S. cerevisiae and 3.0%, m/v, agarose) and a diffusive layer of cellulose (3MM Chr chromatography paper of 25-mm diameter). The effects of some DGT parameters (e.g., immersion time, ionic strength, and pH) were evaluated. Elution of Pb from the binding agent was effectively done with 1.75 mol L(-1) HNO(3). The deployment curve (between 2 and 24 h) was characterized by a significant uptake of Pb (346 ng Pb h(-1)) and good linear regression (R(2) = 0.9757). The experimental results are in excellent agreement with the predicted theoretical curve for mass uptake. Consistent results were found for solutions with ionic strengths of 0.005 mol L(-1) or greater and within a pH range of 4.5-8.5. Interferences from Cu (20:1), Mn (20:1), Fe (20:1), Zn (20:1), Ca (250:1), and Mg (250:1) in Pb retention were negligible. Determination of Pb in spiked river water samples (from the Corumbataí and Piracicaba rivers) performed using the proposed device was in agreement with total dissolved Pb, whereas measurements in seawater suggest that of the various species of Pb present in the samples, only cationic Pb species are adsorbed by the agarose-yeast gel disks. The in situ concentration of Pb obtained at two different sites of the Rio Claro stream (Corumbataí basin) were 1.13 ± 0.01 and 1.34 ± 0.04 μg L(-1). For 72-h deployments, a detection limit of 0.75 μg L(-1) was calculated. The combination of inductively coupled plasma optical emission spectroscopy and in situ deployments of DGT samplers during the 72-h period makes possible the determination of labile Pb in river water.

A rotating disk electrokinetic method for characterizing polyelectrolyte pharmaceutical gels

Charge groups in polyelectrolyte gels can affect the entrapment and release of ionic drugs as well as influencing the stability of colloidal and nanoparticulate drug delivery systems. An accurate knowledge of gel charge properties is therefore important to the understanding and design of such drug delivery systems. Existing rotating disk method for quantifying the surface potential of flat surfaces is based on the classical electrokinetic model that neglects the effect of surface conductivity and is therefore only applicable to ion-impenetrable hard surfaces. This classical electrokinetic model would be inaccurate for polyelectrolyte gel systems involving ion-penetrable charged layers or “soft” surfaces. In this study, we developed a new rotating disk model for characterizing charge properties of ion penetrable soft surfaces and tested it on polyvinyl alcohol (PVA)/polyacrylic acid (PAA), gelatin, and gelatin/PAA polyelectrolyte gels. In addition to classical electrokinetic parameters, the contribution of surface conductivity known to be very significant for soft and ion-penetrable gel surfaces has been taken into account in this new rotating disk model. Based on this new approach, two rotating gel disks of different radius but with identical gel composition and preparation procedures were employed for determining the gel surface potential and density of fixed charge groups. A comparison of the resulting data with that obtained from existing rotating disk model ignoring the surface conductivity reveals a significant underestimation of the gel surface potential and the density of fixed charge groups by the ion-impenetrable hard surface approach. Our results thus confirm that the contribution of surface conductivity is significant in the electrokinetic characterization of polyelectrolyte gels that can be evaluated with our new rotating disk model.

Covalent immobilization of β‐galactosidase on carrageenan coated with chitosan

Abstractβ‐Galactosidase was covalently immobilized to carrageenan coated with chitosan for the hydrolysis of lactose. The chitosan‐carrageenan polyelectrolyte interaction was found to be dependent on the chitosan pH. At pH 4, the chitosan reached its maximum binding of 28.5% (w/w) where the chitosan surface density was 4.8 mg chitosan/cm2 g of carrageenan gel disks, using Muzzarelli method. Glutaraldehyde was used as a mediator to incorporate new functionality, aldehydic carbonyl group, to the bio‐polymers for covalent attachment of β‐galactosidase. The enzyme was covalently immobilized to the biopolymer at a concentration of 2.73 mg protein per g of wet gel. FTIR proved the incorporation of the aldehydic carbonyl group to the carrageenan coated with chitosan at 1720 cm−1. The optimum time for enzyme immobilization was found to be 16 h, after which a plateau was reached. The enzyme loading increased from 2.65 U/g (control gel) to 10.92 U/g gel using the covalent technique.The gel's modification has shown to improve the carrageenan gel thermal stability as well as the immobilized enzyme. For example, the carrageenan gel treated with chitosan showed an outstanding thermal stability at 95°C compared with 35°C for the untreated carrageenan gel. Similarly, the immobilization process shifted the enzyme's optimum temperature from 50°C for the free enzyme towards a wider temperature range 45–55 °C indicating that the enzyme structure is strengthened by immobilization. In brief, the newly developed immobilization method is simple; the carrier is cheap, yet effective and can be used for the immobilization of other enzymes. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Osteogenic differentiation of mesenchymal stem cells in defined protein beads

There is a need to develop improved methods for directing and maintaining the differentiation of human mesenchymal stem cells (hMSC) for regenerative medicine. Here, we present a method for embedding cells in defined protein microenvironments for the directed osteogenic differentiation of hMSC. Composite matrices of collagen I and agarose were produced by emulsification and simultaneous polymerization in the presence of hMSC to produce 30-150 mum diameter hydrogel "beads." The proliferation, morphology, osteogenic gene expression, and calcium deposition of hMSC in bead environments were compared to other two- and three-dimensional culture environments over 14-21 days in culture. Cells embedded within 40% collagen beads exhibited equivalent proliferation rates to those in gel disks, but showed upregulation of bone sialoprotein and increased calcium deposition over 2D controls. Osteocalcin gene expression was not changed in 3D beads and disks, while collagen type I gene expression was downregulated relative to cells in 2D culture. The hydrogel bead format allows controlled cell differentiation and is a cell delivery vehicle that may also enhance vascular invasion and host incorporation. Our results indicate that the application of such beads can be used to promote the osteogenic phenotype in hMSC, which is an important step toward using them in bone repair applications.

Thermosensitive hydrogel coatings: Synthesis and heparin release

AbstractThe synthesis and drug release properties of crosslinked N‐isopropylacrylamide (NiPAAm) copolymer coatings on the surface of a hydrophobic poly(ester‐urethane) tubing were examined. A method was designed to coat hydrophobic polymer surface with a thermosensitive gel layer. Crosslinked NiPAAm copolymer coatings were synthesized using UV‐initiated polymerization. The feasibility of using NiPAAm based gels as heparin releasing thermosensitive coatings was investigated. Heparin, a high molecular weight hydrophilic solute, was loaded into hydrogels using a simple solution sorption technique. The release of heparin from NiPAAm copolymer gel coatings was compared to that of crosslinked NiPAAm copolymers. The gel coatings demonstrated a more gradual and prolonged heparin release as compared to gel disks of the same composition.

Kinetics of one-dimensional gel swelling and collapse for large volume change

The kinetics of one-dimensional gel swelling and collapse for large volume changes were described by a Fickian model which accounts for the movement of the gel surface. For a constant mutual diffusion coefficient, D m , the fractional approach to equilibrium, F, is a function only of dimensionless time, τ 0, and the equilibrium volume ratio, Φ. Gel collapse is faster than swelling when D m is the same for both. Swelling curves, the variation of F with ✓τ 0 , were computed for planar, cylindrical and spherical geometries with constant D m . For slabs the swelling curves are initially linear for all Φ values, while for cylinders and spheres the swelling curves are linear for small Φ values, but sigmoidal for Φ ≥ 2.5. For 0.5 ≤ Φ ≤ 2, a simple method gives experimental values of D m which account for the movement of the gel boundary. Experimental data for weakly ionic poly( N-isopropylacrylamide) gel spheres in water ( Φ = 55) and for non-ionic poly( N-isopropylacrylamide) gel disks in water ( Φ = 7.7) were well fitted by the model.

Hypoxic contraction of contractile interstitial cells isolated from bovine lung.

Although contractile interstitial cells (CIC) in the alveolar septum have been suggested to be involved in hypoxic pulmonary vasoconstriction (HPV), direct demonstration of cellular contraction under hypoxia has been lacking. To achieve this, we purified CIC from collagenase-dissociated bovine lung cells and examined the response of these cells to hypoxia. Prostaglandin (PG) F synthase served as a marker of CIC, and the isolated PGF synthase-positive cells were shown to preserve the ultrastructural features characteristic of CIC, most notably bundles of microfilaments. Isolated CIC seeded onto collagen gel disks became embedded and formed a lattice network with collagen fibrils. Exposure of these CIC-bearing gels to hypoxia (PO2 = 20-40 Torr) evoked a reversible reduction in gel volume, as assessed by measuring the surface area of the gel disks photographically. Thus CIC were shown to contract under hypoxia, providing the supportive evidence for the involvement of CIC in HPV.

Concentrating Cellulases Using a Temperature‐Sensitive Hydrogel: Effect of Gel Particle Size and Geometry

AbstractA temperature‐sensitive poly (N‐isopropylacrylamide) hydrogel was used to concentrate cellulases from Trichoderma reesei. The effect of gel size and geometry on separation efficiency and weight change rate was studied. Gel weight change was reproducible over six cycles of short swelling and collapsing (2 h each) experiments, but the gel weight change capacity of small and large cubes was 90% and 62% of small extruded gel, respectively. The gel weight change capacity of large extruded gel and chopped gel was comparable to that of small extruded gel. Cellulase separation efficiency increased up to 64% for large cubes, but it was lower than 80–97% for comparably sized solutes reported in the literature. Small extruded gel reached its equilibrium weight in 2–3 h, but it took more than 200 times longer for gel disks to reach equilibrium weights. Initial solution flux (surface‐specific water release/sorption rate) during swelling and collapsing was 1065–2450 g/m2·h, but flux decreased rapidly with time. Skin formation was partially responsible for the slower weight change rate of larger gels, but chopped gel also formed skin at collapse temperatures higher than 37 °C. Skin formation was not observed for small extruded gel up to 50 °C. During gel disk collapsing experiments, transparent bubbles trapping pressurized water initially were observed all over the gel surface, and some of the bubbles on the disk edge did not collapse until the gel approached an equilibrium weight.