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ABSTRACT: A set of glutaraldehyde (GA) cross-linked poly(vinyl alcohol)/activated carbon (PVA/GA/AC) composites prepared in the form of monolithic rods using a cryogelation technique and studied using adsorption, mercury porosimetry, SEM and quantum chemistry methods displays porosity similar to that of PVA/GA cryogel at a high GA content (content ratio GA/AC = 1 and GA/PVA = 0.2). GA-cross-linked PVA multilayer coverage is an effective barrier for adsorption on AC particles. Variations in surface chemistry (AC initial and oxidized in air at 300oC for 12 h) and content (14 - 62.5 %w/w) of ACs in PVA/GA/AC composites relatively weakly affect their textural characteristics at a high GA content (specific surface area SBET < 120 m2/g, pore volume Vp < 0.35 cm3/g). However, PVA/GA/AC composite rods formed with a lower concentration of GA (content ratio GA/AC = 1/6 and GA/PVA = 1/10) have significantly greater SBET (~500 m2/g) and Vp (> 0.55 cm3/g) values because of improved accessibility of the AC surface. This provides better adsorption of methylene blue as a probe compound.
ACS Applied Materials & Interfaces 10/2012; · 4.53 Impact Factor
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ABSTRACT: Drug-eluting beads (DEBs) are becoming a mainstay locoregional therapy for hepatic malignancies but are currently loaded with single drugs alone. Here, we wished to prepare DEB containing different drug combinations, to screen their efficacy using an in-vitro cell culture assay and to include any promising combinations that demonstrate additive efficacy in an in-vivo model of locoregional tumour treatment. A modified in-vitro assay was used based upon the use of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) with either HepG2 liver cancer or PSN1 pancreatic cancer cell lines. The comparative cytotoxicity of DEB combinations prepared containing doxorubicin, irinotecan, topotecan and rapamycin was evaluated. Those combinations that demonstrated an additive cytotoxicity effect were investigated in vivo using a nude mouse xenograft model of pancreatic cancer. Although many of the DEB combinations showed either no effect or a slight antagonistic effect, the combination of doxorubicin and rapamycin DEBs demonstrated synergistic activity. On the basis of these findings, a method was developed to prepare a doxorubicin/rapamycin dual-loaded DEB, which was shown to possess the same drug-loading capacities, drug elution properties and HepG2 cell cytotoxicity synergy as the single drug-loaded DEB combination. Evaluation of this dual-loaded combination DEB versus the respective single drug-loaded DEBs in a mouse xenograft model of pancreatic cancer showed an equivalent tumour volume reduction as the doxorubicin DEB, but with less toxicity than the rapamycin DEB. The doxorubicin/rapamycin combination DEB offers great potential for enhanced efficacy in the locoregional treatment of malignant tumours.
Anti-cancer drugs 04/2012; 23(4):355-69. · 2.23 Impact Factor
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ABSTRACT: In the course of severe pathological conditions, such as acute liver failure and sepsis, toxic metabolites and mediators of inflammation are released into the patient's circulation. One option for the supportive treatment of these conditions is plasmapheresis, in which plasma, after being separated from the cellular components of the blood, is cleansed by adsorption of harmful molecules on polymers or activated carbon. In this work, the adsorption characteristics of activated carbon beads with levels of activation ranging from 0 to 86% were assessed for both hydrophobic compounds accumulating in liver failure (bilirubin, cholic acid, phenol and tryptophan) and cytokines (tumor necrosis factor α and interleukin-6). Progressive activation resulted in significant gradual reduction of both bulk density and mean particle size, in an increase in the specific surface area, and to changes in pore size distribution with progressive broadening of micropores. These structural changes went hand in hand with enhanced adsorption of small adsorbates, such as IL-6 and cholic acid and, to a lesser extent, also of large molecules, such as TNF-α.
Biomacromolecules 08/2011; 12(10):3733-40. · 5.48 Impact Factor
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ABSTRACT: The textural and adsorption characteristics of a series of activated carbons (ACs), porous poly(vinyl alcohol) (PVA) gels, and PVA/AC composites were studied using scanning electron microscopy, mercury porosimetry, adsorption of nitrogen (at 77.4 K), cationic methylene blue (MB), anionic methyl orange (MO), and Congo red (CR) from the aqueous solutions. Dye-PVA-AC-water interactions were modeled using the semiempirical quantum chemical method PM6. The percentage of dye removed (C(rem)) by the ACs was close to 100% at an equilibrium concentration (C(eq)) of less than 0.1 mM but decreased with increasing dye concentration. This decrease was stronger at C(eq) of less than 1 mM, and C(rem) was less than 50% at a C(eq) of 10-20 mM. For PVA and the PVA/AC composite containing C-7, the C(rem) values were minimal (<75%). The free energy distribution functions (f(ΔG)) for dye adsorption include one to three peaks in the -ΔG range of 1-60 kJ/mol, depending on the dye concentration range used and the spatial, charge symmetry of the hydrated dye ions and the structural characteristics of the adsorbents. The f(ΔG) shape is most complex for MO with the most asymmetrical geometry and charge distribution and adsorbed at concentrations over a large C(eq) range. For symmetrical CR ions, adsorbed over a narrow C(eq) range, the f(ΔG) plot includes mainly one narrow peak. MB has a minimal molecular size at a planar geometry (especially important for effective adsorption in slit-shaped pores) which explains its greater adsorptive capacity over that of MO or CR. Dye adsorption was greatest for ACs with the largest surface area but as molecular size increases adsorption depends to a greater extent on the pore size distribution in addition to total and nanopore surface areas and pore volume.
Journal of Colloid and Interface Science 02/2011; 358(2):582-92. · 3.07 Impact Factor
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ABSTRACT: The porous structure and the state of the water are two main factors which define the vast applications of hydrogels in the life science arena. The structural characterisation and water state in hydrogels produced by the cryogelation of poly(hydroxyethyl methacrylate) and gelatine were undertaken using different techniques. Images obtained using confocal laser scanning and multiphoton microscopies were analysed using ImageJ/Fiji software to estimate the total porosity, specific surface area and pore size and wall thickness distribution functions of each of the hydrogels. The hydration properties and structural characteristics of the nanopore component of the polymer and protein hydrogels were analysed using DSC, 1H NMR spectroscopy and cryoporometry and modelled using the PM6 quantum chemical method. The hydrogels produced by cryogelation were shown to have a large macropore volume, high pore interconnectivity and small specific surface area. The main portion of water was shown to be attributable to bulk water located within macropores. The relative amounts of bound water in the hydrogels were demonstrated to be small (<10 wt% of bulk water) making macroporous hydrogels an attractive system for biological applications. An understanding of the parameters studied here is important for the future engineering of cryogels for biological applications.
Soft Matter 01/2011; 7(9):4276-4283. · 4.39 Impact Factor
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ABSTRACT: DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40-45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC(50) for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 microM compared to 28.1 and 19.2 microM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml(-1), like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3-6.6 mg were shown to be well-tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83-1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2-0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity.
Journal of Materials Science Materials in Medicine 09/2010; 21(9):2683-90. · 2.32 Impact Factor
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ABSTRACT: High molecular weight alginate beads with 59% mannuronic acid content or 68% guluronic acid were prepared using a droplet generator and crosslinked in calcium chloride. The alginate beads were compared to current embolisation microspheres for compressibility and monitored over 12 weeks for size and weight change at 37 degrees C in low volumes of ringers solutions. A sheep uterine model was used to analyse bead degradation and inflammatory response over 12 weeks. Both the in vitro and in vivo data show good delivery, with a compressibility similar to current embolic beads. In vitro, swelling was noted almost immediately and after 12 weeks the first signs of degradation were noted. No difference was noted in vivo. This study has shown that high molecular weight alginate gel beads were well tolerated by the body, but beads associated with induced thrombi were susceptible to inflammatory cell infiltration. The beads were shown to be easy to handle and were still observable after 3 months in vivo. The beads were robust enough to be delivered through a 2.7 Fr microcatheter. This study has demonstrated that high molecular weight, high purity alginate bead can be considered as semi-permanent embolisation beads, with the potential to bioresorb over time.
Journal of Materials Science Materials in Medicine 07/2010; 21(7):2243-51. · 2.32 Impact Factor
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ABSTRACT: A prototype in-line filtration/adsorption device has been developed using novel synthetic pyrolysed carbon monoliths with controlled mesoporous domains of 2-50nm. Porosity was characterized by SEM and porosimetry. Removal of inflammatory cytokines TNF, IL-6, IL-1beta and IL-8 was assessed by filtering cytokine spiked human plasma through the walls of the carbon modules under pressure. The effect of carbon filtration on plasma clotting response and total plasma protein concentration was also assessed. Significant removal of the cytokines IL-6, IL-1beta and IL-8 was observed. Initially marked TNF removal diminished over time. The coagulation studies indicated that the carbon device does not exacerbate the propensity of blood plasma to clot. The total plasma protein concentration remained constant. The device offers a broader approach to the treatment of systemic inflammatory response syndrome (SIRS) by the removal of inflammatory mediators central to its progression.
Biomaterials 05/2008; 29(11):1638-44. · 7.40 Impact Factor
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Alexander E Ivanov,
John Eccles,
Homayon Ahmad Panahi,
Ashok Kumar,
Marina V Kuzimenkova,
Lars Nilsson,
Björn Bergenståhl,
Nick Long, Gary J Phillips,
Sergey V Mikhalovsky,
Igor Yu Galaev,
Bo Mattiasson
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ABSTRACT: Boronate-containing polymer brushes were synthesized by free radical copolymerization of N,N-dimethylacrylamide (DMAA) and N-acryloyl-m-phenylboronic acid (NAAPBA) (9:1) on the surface of 3-mercaptopropyl-silylated glass plates and capillaries. The brushes were characterized with time-of-flight secondary ion mass-spectrometry (ToF SIMS), atomic force microscopy and contact angle measurements. Fructose caused a well-expressed drop spreading on the surface of copolymer-grafted glass, due to the strong interaction with the boronate groups. Sedimentation of murine hybridoma cells M2139 or human myeloid leukemia cells KG1 onto the DMAA-NAAPBA copolymer-grafted glass plates from 10 mM phosphate buffer solution (pH 8.0) resulted in the cell adhesion. The adhered M2139 and KG1 cells could be quantitatively detached from the grafted plates with 0.1 M fructose, which competed with cell surface carbohydrates for binding to the boronates. Evaluation of the binding strength between M2139 cells and the copolymer brush was performed by exposure of the adhered cells to a shear stress. Detachment of a fraction of 18% of the adhered M2139 cells was obtained at a shear force of 1400-2800 pN/cell generated by the running phosphate buffer (pH 8.0), whereas the remaining adhered cells (70%) could be detached with 0.1 M fructose dissolved in the same buffer. Possible applications of the boronate-containing polymer brushes to affinity cell separation can be based upon the facile recovery of the attached cells.
Journal of Biomedical Materials Research Part A 03/2008; 88(1):213-25. · 2.63 Impact Factor
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ABSTRACT: DC Bead is a sulfonate-modified, PVA-based microspherical embolisation agent approved for the treatment of hypervascular tumours and arterio-venous malformations. The beads have previously been shown to actively sequester oppositely charged drugs, such as doxorubicin hydrochloride (dox) by an ion-exchange mechanism. In order to characterise the release kinetics and predict the in vivo behaviour of drug eluting beads (DEB), two elution methods were utilised. The first, an application of the USP dissolution method Type II - Apparatus, enables study of the complete elution of loaded DC Bead in less than 4 h, allowing relatively rapid comparison to be made between different products and formulations. Release data obtained using this method were fitted to first order kinetics (R (2) > 0.998) and the elution constants shown to increase with the total surface area of the beads exposed to the elution medium. Diffusion coefficients were calculated adopting the Fickian diffusion model, which predicted slow elution rates under physiological conditions. The second method involved the use of a T-Apparatus where the drug experiences an element of diffusion through a static environment. This method was developed to resemble the in vivo situation in embolisation procedures more closely. Slow release of dox from DC Bead with half-lives over 1,500 h were predicted for all size ranges using a slow release model. A strong linear relationship was found between the release data from T-Apparatus and pharmacokinetic data obtained from patients treated with DC Bead loaded with dox in transarterial chemoembolisation (TACE) procedures. These data indicated a Level A in vitro-in vivo correlation (IVIVC) for the first 24 h post embolisation. Both systems developed were automated and good reproducibility was obtained for all samples, demonstrating the usefulness of these elution techniques for product development and comparative testing.
Journal of Materials Science Materials in Medicine 02/2008; 19(2):767-75. · 2.32 Impact Factor
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ABSTRACT: DC Bead is a FDA cleared embolisation device for the treatment of hypervascular tumours and arteriovenous malformations. This product is currently evaluated in a number of centres in Europe as an embolic device for transarterial chemoembolisation (TACE). The beads consist of poly(vinyl alcohol) microspheres modified with sulfonic acid groups and are available at different size ranges varying from 100 to 900 microm in diameter. The beads were shown to actively sequester doxorubicin hydrochloride (dox) from solution in a time dependent upon the dose of the drug and size of the beads. Drug uptake was by an ion-exchange mechanism, and in the absence of other ions in solution, the beads could load a maximum of around 40 mg dox/mL hydrated beads, with >99% of drug being sequestered from the solution. A loading of 25 mg dox/mL beads was recommended as providing a practical therapeutic dose and optimum handling characteristics. There was a decrease in equilibrium water content of the beads with increasing dox loading, which resulted in a decrease in the average diameter of the beads and an increase in the compressive modulus. The deliverability properties, however, were not affected after drug loading. Using a variety of microscopic methods, the drug was shown to be distributed throughout the bead structure, but concentrated in the outer 20 microm surface layer, a feature related to the method of synthesis. This study characterises the properties of DC Bead loaded with dox with respect to important characteristics in embolisation and demonstrates the potential of this drug device combination for the treatment of hypervascular tumours such as hepatocellular carcinoma.
Journal of Materials Science Materials in Medicine 10/2007; 18(9):1691-9. · 2.32 Impact Factor
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ABSTRACT: Porous carbons can be used for the purification of various bio-fluids, including the cleansing blood of inflammatory mediators in conditions such as sepsis or auto-immune diseases. Here we show that the control of pore size in carbons is a key factor to achieving efficient removal of cytokines. In particular, the surface area accessible by the protein governs the rate and effectiveness of the adsorption process. We demonstrate that novel mesoporous carbon materials synthesized from ternary MAX-phase carbides can be optimized for efficient adsorption of large inflammatory proteins. The synthesized carbons, having tunable pore size with a large volume of slit-shaped mesopores, outperformed all other materials or methods in terms of efficiency of TNF-alpha removal and the results are comparable only with highly specific antibody-antigen interactions.
Biomaterials 01/2007; 27(34):5755-62. · 7.40 Impact Factor
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Carol A Howell,
Susan R Sandeman, Gary J Phillips,
Andrew W Lloyd,
J Graham Davies,
Sergey V Mikhalovsky,
Steve R Tennison,
Anthony P Rawlinson,
Oleksandr P Kozynchenko,
Hannah L H Owen,
John D S Gaylor,
Jennifer J Rouse,
James M Courtney
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ABSTRACT: This study investigated a range of phenol-formaldehyde-aniline-based pyrolysed carbon matrices and their component materials, for their ability to adsorb a range of inflammatory cytokines crucial to the progression of sepsis. The efficiency of adsorption of the target molecules from human plasma was assessed and compared to that of Adsorba 300C, a commercially available cellulose-coated activated charcoal. Results indicate that a number of the primary carbon/resin materials demonstrate efficient adsorption of the cytokines studied here (TNF, IL-6 and IL-8), comparable to other adsorbents under clinical investigation. Our findings also illustrate that these adsorbent capabilities are retained when the primary particles are combined to form a pyrolysed carbon matrix. This capability will enable the engineering of the carbon matrix porosity allowing a blend of carbonised particle combinations to be tailored for maximum adsorption of inflammatory cytokines. The present findings support further investigation of this carbon material as a combined carbon-based filtration/adsorbent device for direct blood purification.
Biomaterials 11/2006; 27(30):5286-91. · 7.40 Impact Factor
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Susan R Sandeman,
Carol A Howell, Gary J Phillips,
Andrew W Lloyd,
J Graham Davies,
Sergey V Mikhalovsky,
Steve R Tennison,
Andrew P Rawlinson,
Oleksandr P Kozynchenko,
Hannah L H Owen,
John D S Gaylor,
Jennifer J Rouse,
James M Courtney
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ABSTRACT: The aim of the present study was to conduct a preliminary investigation into the blood biocompatibility of a novel, uncoated carbon for use in a filtration/adsorption device for the treatment of sepsis. Carbon well prototypes were manufactured from phenol-formaldehyde-aniline-based pyrolysed carbons using monolithic polymer technology. Inflammatory blood cell and plasma protein mediation of the inflammatory response were evaluated using the novel carbon prototypes and compared with dialyser membrane and tissue culture plate controls. Assays determining monocyte and granulocyte adhesion, platelet adhesion and activation, granulocyte activation and complement activation were performed. Preliminary findings suggest an adsorptive but passivating carbon surface. Moderate levels of monocyte and granulocytes adhesion were seen in conjunction with adsorption of plasma proteins to the carbon surface. Activation of granulocyte and adherent platelets was not detected and the complement cascade was not activated by the carbons, indicating a surface compatible with blood contact. The results support the further development of the proposed carbon-based device for the treatment of sepsis.
Biomaterials 01/2006; 26(34):7124-31. · 7.40 Impact Factor
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ABSTRACT: Major challenges associated with nano-sized drug delivery systems include removal from systemic circulation by phagocytic cells and controlling appropriate drug release at target sites. 2-methacryloyloxyethyl phosphorylcholine (MPC) has been copolymerised in turn with two pH responsive comonomers (2-(diethylamino)ethyl methacrylate (DEA) and 2-(diisopropylamino)ethyl methacrylate (DPA), to develop novel biocompatible drug delivery vehicles. Micelles were prepared from a series of copolymers with varying block compositions and their colloidal stability and dimensions were assessed over a range of solution pH using photon correlation spectroscopy. The drug loading capacities of these micelles were evaluated using Orange OT dye as a model compound. The cytotoxicity of the micelles was assessed using an in vitro assay. The MPC-DEA diblock copolymers formed micelles at around pH 8 and longer DEA block lengths allowed higher drug loadings. However, these micelles were not stable at physiological pH. In contrast, MPC-DPA diblock copolymers formed micelles of circa 30 nm diameter at physiological pH. In vitro assays indicated that these MPC-DPA diblock copolymers had negligible cytotoxicities. Thus novel non-toxic biocompatible micelles of appropriate size and good colloidal stability with pH-modulated drug uptake and release can be readily produced using MPC-DPA diblock copolymers.
Journal of Controlled Release 06/2005; 104(2):259-70. · 5.73 Impact Factor
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ABSTRACT: The success or failure of medical implants often depends on the cell-surface behavior after implantation of the device. This study investigated the use of woven carbon fabric, which had been sonoelectrochemically coated with calcium phosphate, to enhance bone cell attachment and proliferation in vitro. Human osteoblast-like cells, MG63, were used to study the interactions between cells and the material and assess the cytotoxicity of the substrates. The cytotoxicity of the materials was assessed using an MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt)) assay to determine the viability of the osteoblast-like MG63 cells in direct contact with the carbon fabric or calcium phosphate coated carbon fabrics, and to assess the cytotoxicity of extracts from these materials. The morphology of the surface adherent cells was assessed by scanning electron microscopy (SEM). Results showed that neither carbon fabrics nor calcium phosphate coated materials were cytotoxic. Furthermore, cell attachment and proliferation were enhanced by coating carbon fabrics with calcium phosphate. SEM showed that the cells had a normal morphology and were well spread similar to those seen in the tissue culture plate control. These flexible calcium phosphate coated fabrics could, therefore, have uses in the reconstruction of bone in orthopaedic and dental surgery.
New Carbon Materials. 23(2):139-143.
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ABSTRACT: Calcium phosphate coatings were directly deposited on carbon fabric cloths, using a novel method, sonoelectrochemical deposition, in aqueous electrolytes containing calcium and phosphate ions, at pH ∼4.7, and at a relatively low temperature of 50°C, with the aim of investigating the usefulness of the resulting composites for reconstruction of bone defects. The deposits were characterized with the help of infrared spectroscopy and scanning electron microscopy, with energy dispersive X-ray microanalysis. Human osteoblast-like cells (MG63) were used to investigate the cell/biomaterial interaction in vitro. Results showed that the composition and the morphologies of phosphate deposits were dramatically influenced by the application of ultrasound, which appeared to offer a number of potential advantages over the simple electrochemical processes. In vitro MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay confirmed the significant improvement in the cell attachment, and proliferation was because of the phosphate deposits prepared by sonoelectrodeposition rather than the traditional silent one.
New Carbon Materials.
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Carol A. Howell,
Susan R. Sandeman, Gary J. Phillips,
Andrew W. Lloyd,
J. Graham Davies,
Sergey V. Mikhalovsky,
Steve R. Tennison,
Anthony P. Rawlinson,
Oleksandr P. Kozynchenko,
Hannah L.H. Owen,
John D.S. Gaylor,
Jennifer J. Rouse,
James M. Courtney
[show abstract]
[hide abstract]
ABSTRACT: This study investigated a range of phenol–formaldehyde–aniline-based pyrolysed carbon matrices and their component materials, for their ability to adsorb a range of inflammatory cytokines crucial to the progression of sepsis. The efficiency of adsorption of the target molecules from human plasma was assessed and compared to that of Adsorba® 300C, a commercially available cellulose-coated activated charcoal. Results indicate that a number of the primary carbon/resin materials demonstrate efficient adsorption of the cytokines studied here (TNF, IL-6 and IL-8), comparable to other adsorbents under clinical investigation. Our findings also illustrate that these adsorbent capabilities are retained when the primary particles are combined to form a pyrolysed carbon matrix. This capability will enable the engineering of the carbon matrix porosity allowing a blend of carbonised particle combinations to be tailored for maximum adsorption of inflammatory cytokines. The present findings support further investigation of this carbon material as a combined carbon-based filtration/adsorbent device for direct blood purification.
Biomaterials.
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ABSTRACT: This study investigated the cytotoxic potential of novel activated carbon adsorbents (MAST Carbon International Ltd.) developed for medical applications such as extracorporeal therapies. Carbon adsorbents were assessed for their in vitro cytotoxicity against a V79 cell line using a material extraction method in combination with a colony formation assay. Results were compared to those from a commercially available cellulose-coated carbon adsorbent, developed for direct haemoperfusion. Initial findings demonstrated an inhibition of colony formation and an apparent cytotoxic effect. However, it was found that this inhibition occurred as a result of protein and ion adsorption by carbon materials possessing large surface area and highly developed porous structure. Consequently, these essential nutrients were unavailable to the cells during colony formation. Modifications to the cytotoxicity assessment methods were required in order to take into account nutrient loss. Subsequently it was determined that the carbon materials do not show a cytotoxic response towards the V79 cell line under the modified conditions employed. The suggested approach may be useful in the assessment of other biomaterials such as carbon nanotubes and other nanoparticles which possess large surface area. The preliminary data support the ongoing investigation of these adsorbents as candidates for use in extracorporeal therapies.
Carbon.
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Susan R. Sandeman,
Carol A. Howell, Gary J. Phillips,
Andrew W. Lloyd,
J. Graham Davies,
Sergey V. Mikhalovsky,
Steve R. Tennison,
Andrew P. Rawlinson,
Oleksandr P. Kozynchenko,
Hannah L.H. Owen,
John D.S. Gaylor,
Jennifer J. Rouse,
James M. Courtney
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present study was to conduct a preliminary investigation into the blood biocompatibility of a novel, uncoated carbon for use in a filtration/adsorption device for the treatment of sepsis. Carbon well prototypes were manufactured from phenol–formaldehyde–aniline-based pyrolysed carbons using monolithic polymer technology. Inflammatory blood cell and plasma protein mediation of the inflammatory response were evaluated using the novel carbon prototypes and compared with dialyser membrane and tissue culture plate controls. Assays determining monocyte and granulocyte adhesion, platelet adhesion and activation, granulocyte activation and complement activation were performed. Preliminary findings suggest an adsorptive but passivating carbon surface. Moderate levels of monocyte and granulocytes adhesion were seen in conjunction with adsorption of plasma proteins to the carbon surface. Activation of granulocyte and adherent platelets was not detected and the complement cascade was not activated by the carbons, indicating a surface compatible with blood contact. The results support the further development of the proposed carbon-based device for the treatment of sepsis.
Biomaterials.
