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Biodegradable alginate antibiotic beads.

The authors investigated the poly-L-lysine-coated alginate beads as an antibiotic delivery system for the treatment of various surgical infections. The sodium alginate was mixed with vancomycin, coated with poly-L-lysine, and lyophilized to form five types of the biodegradable antibiotic beads. Type I, 2.5% alginate, nonpoly-L-lysine coated and nonlyophilized; Type II, 2.5% alginate, poly-L-lysine coated but nonlyophilized; Type III, 2.5% alginate, poly-L-lysine coated and lyophilized; Type IV, 5% alginate, poly-L-lysine coated and lyophilized; and Type V, 7.5% alginate, poly-L-lysine coated and lyophilized. Cytotoxicity of the alginate beads to fibroblasts and HeLa cells was evaluated by the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] colorimetric assay. A study of in vitro elution of vancomycin of the alginate antibiotic beads was performed. The results suggested that the alginate antibiotic beads present no obvious toxic risk to their use as a drug delivery system. The concentration of vancomycin in these five types of beads was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for 9,11,12, 14, and 17 days respectively. The release was most marked during the first 3 days. The duration of antibiotic release was prolonged by using techniques of poly-L-lysine coating, lyophilization, and by increasing the content of alginate. This study offers a biodegradable delivery system of antibiotics to treat various surgical infections.

Alginates↗

Alginic acid has anti-anaphylactic effects and inhibits inflammatory cytokine expression via suppression of nuclear factor-kappaB activation.

BACKGROUND: Alginic acid is comprised of complex polymerized polysaccharides, and can be chemically extracted from seaweed. Alginic acid has an inhibitory effect on histamine release, but its molecular mechanisms are not well understood. OBJECTIVE: To investigate the effect of alginic acid on the mast cell-mediated anaphylactic and inflammatory reaction using in vivo and in vitro models and elucidate its molecular mechanisms. MATERIALS AND METHOD: The effect of alginic acid on an allergy model was analysed by anaphylaxis, a histidine decarboxylase (HDC) assay, and a histamine assay. Cytokine production was analysed by means of ELISA. Cytokine expression was analysed by means of RT-PCR, and Western blotting. Transcription factor activity was analysed by a luciferase assay and a transcription factor-enzyme linked immunoassay. RESULTS: Alginic acid dose dependently inhibited compound 48/80-induced systemic anaphylaxis with doses of 0.25-1 g/kg 1 h (P<0.01, n=6) and significantly inhibited passive cutaneous anaphylaxis by 54.8%. Alginic acid (0.01-1 microg/mL) inhibited histamine release from serum and peritoneal mast cells (P<0.01). All these effects were stronger than those of disodium cromoglycate (DSCG), the reference drug tested. Alginic acid also inhibited HDC expression and activity on the phorbol myristate acetate (PMA)+A23187-stimulated human mast cell line, HMC-1 cells. Moreover, alginic acid significantly inhibited the production of PMA+A23187-induced inflammatory cytokines, IL-1beta and TNF-alpha, but not that of IL-6 or IL-8. In activated HMC-1 cells, the expression level of nuclear factor (NF)-kappaB/Rel A protein increased in the nucleus, whereas the level of NF-kappaB/Rel A in the nucleus was decreased by alginic acid treatment. In addition, alginic acid (0.01 microg/mL) decreased the PMA+A23187-induced luciferase activity and DNA-binding activity. CONCLUSION: The present results indicate that alginic acid has potent anti-anaphylactic and anti-inflammatory properties.

Alginates↗

Molecular identification of oligoalginate lyase of Sphingomonas sp. strain A1 as one of the enzymes required for complete depolymerization of alginate.

A bacterium, Sphingomonas sp. strain A1, can incorporate alginate into cells through a novel ABC (ATP-binding cassette) transporter system specific to the macromolecule. The transported alginate is depolymerized to di- and trisaccharides by three kinds of cytoplasmic alginate lyases (A1-I [66 kDa], A1-II [25 kDa], and A1-III [40 kDa]) generated from a single precursor through posttranslational autoprocessing. The resultant alginate oligosaccharides were degraded to monosaccharides by cytoplasmic oligoalginate lyase. The enzyme and its gene were isolated from the bacterial cells grown in the presence of alginate. The purified enzyme was a monomer with a molecular mass of 85 kDa and cleaved glycosidic bonds not only in oligosaccharides produced from alginate by alginate lyases but also in polysaccharides (alginate, polymannuronate, and polyguluronate) most efficiently at pH 8.0 and 37 degrees C. The reaction catalyzed by the oligoalginate lyase was exolytic and thought to play an important role in the complete depolymerization of alginate in Sphingomonas sp. strain A1. The gene for this novel enzyme consisted of an open reading frame of 2,286 bp encoding a polypeptide with a molecular weight of 86,543 and was located downstream of the genes coding for the precursor of alginate lyases (aly) and the ABC transporter (algS, algM1, and algM2). This result indicates that the genes for proteins required for the transport and complete depolymerization of alginate are assembled to form a cluster.

Alginates↗

Calcium alginate provides a high degree of embolization in aneurysm models: a specific comparison to coil packing.

OBJECTIVE: Although flexible, current coils do not fill intracranial aneurysms to a high degree, and questions remain regarding their thrombogenic capacity. We evaluated the usefulness of calcium alginate as an embolic material for endovascular embolization in aneurysm models. METHODS: We assessed three endovascular methods of instilling calcium alginate into 10-mm sidewall and 7-mm bifurcation glass aneurysm models using a balloon catheter to seal the aneurysm orifice: 1) instillation of alginate and subsequent instillation of the reactive component calcium chloride (CaCl(2)) via a single-lumen catheter, 2) simultaneous instillation of alginate and CaCl(2) via a side-by-side double-lumen catheter, and 3) instillation of alginate mixed with CaCl(2) delivered from a concentric-tube microcatheter. A 13-mm sidewall silicon aneurysm model was used to measure and compare the volume of calcium alginate occupying the aneurysm models. RESULTS: Instillation Method 1 did not achieve optimal filling of the aneurysm with calcium alginate. The percentage volumes of calcium alginate occupying the aneurysm were 69.2 +/- 7.7% and 84.6 +/- 5.4% for instillation Methods 2 and 3, respectively. In Method 3, calcium alginate began gelation upon leaving the catheter, entered the aneurysms in a strand form, and gelled to a mass that filled the aneurysm while conforming to its inner contour. CONCLUSION: Calcium alginate fills aneurysm models to a significantly higher degree than published results of the space filled by coils. Instillation of calcium alginate, especially in strand form, may produce an embolization that better fills and conforms to the contour of aneurysms compared with coils.

Alginates↗

Alginate dressings in surgery and wound management--Part 1.

Large quantities of alginate dressings are used each year to treat exuding wounds, such as leg ulcers, pressure sores and infected surgical wounds. Originally these dressings were a loose fleece formed primarily from fibres of calcium alginate. More recently they have been developed so that the fibres have been entangled to form a product with more cohesive structure, which increases the fabric's strength when it is soaked with exudate or blood. Some products also contain a significant proportion of sodium alginate to improve the gelling properties of the dressing in use. Other dressings have been produced from freeze-dried alginate. Once in contact with an exuding wound, an ion-exchange reaction takes place between the calcium ions in the dressing and sodium ions in serum or wound fluid. When a significant proportion of the calcium ions on the fibre have been replaced by sodium, the fibre swells and partially dissolves forming a gel-like mass. The degree of swelling is determined principally by the chemical composition of the alginate, which depends on its botanical source. Although it is recognised that the differences between the various brands of dressings may influence their handling characteristics--particularly when wet--it is generally assumed that these differences are of limited relevance to the dressing's performance clinically or at a cellular level. There is some evidence to suggest, however, that these assumptions may be wrong and that alginates may influence wound healing in a number of ways not yet fully understood. This three-part review of the literature encompasses the history, origin, structure, chemistry and clinical applications of alginates and alginate dressings. This review reveals that, despite their widespread use, alginates have been the subject of very few well-controlled clinical studies. There is fairly convincing evidence, however, that they do offer advantages over more traditional dressings for at least some clinical indications. It has also become obvious that there is a general lack of understanding about the importance of secondary dressing systems that must be used in with alginate dressings. Careful examination of the design and outcomes of the published studies suggests that the choice of both the primary alginate dressing and the secondary dressing can play a major role in determining treatment outcomes.

Alginates↗

Protein release from alginate matrices.

There are a variety of both natural and synthetic polymeric systems that have been investigated for the controlled release of proteins. Many of the procedures employed to incorporate proteins into a polymeric matrix can be harsh and often cause denaturation of the active agent. Alginate, a naturally occurring biopolymer extracted from brown algae (kelp), has several unique properties that have enabled it to be used as a matrix for the entrapment and/or delivery of a variety of biological agents. Alginate polymers are a family of linear unbranched polysaccharides which contain varying amounts of 1,4'-linked beta-D-mannuronic acid and alpha-L-guluronic acid residues. The residues may vary widely in composition and sequence and are arranged in a pattern of blocks along the chain. Alginate can be ionically crosslinked by the addition of divalent cations in aqueous solution. The relatively mild gelation process has enabled not only proteins, but cells and DNA to be incorporated into alginate matrices with retention of full biological activity. Furthermore, by selection of the type of alginate and coating agent, the pore size, degradation rate, and ultimately release kinetics can be controlled. Gels of different morphologies can be prepared including large block matrices, large beads (>1 mm in diameter) and microbeads (<0.2 mm in diameter). In situ gelling systems have also been made by the application of alginate to the cornea, or on the surfaces of wounds. Alginate is a bioadhesive polymer which can be advantageous for the site specific delivery to mucosal tissues. All of these properties, in addition to the nonimmunogenicity of alginate, have led to an increased use of this polymer as a protein delivery system. This review will discuss the chemistry of alginate, its gelation mechanisms, and the physical properties of alginate gels. Emphasis will be placed on applications in which biomolecules have been incorporated into and released from alginate systems.

Journal Article↗

Human neutrophil elastase inhibition with a novel cotton-alginate wound dressing formulation.

Occlusion and elasticity were combined in a novel cotton-based alginate dressing containing a nontoxic elastase inhibitor. Cotton gauzes were modified with a textile finishing process for incorporating alginate to yield a dressing material that retains elasticity while enhancing absorption. The algino-cellulose conjugates were formed through citric acid crosslinking of cellulose and alginate. The alginate-citrate finishes were applied to cotton gauzes in various formulations containing citric acid, sodium hypophosphite, and polyethylene glycol. The modified gauzes contain a citrate conjugate of alginate and cellulose that gels upon hydration. The alginate-citrate finishes were combined with the neutrophil elastase inhibitor, oleic acid, to demonstrate the ability of the algino-cellulose fibers to release the inhibitor and neutralize destructively high levels of neutrophil elastase found in nonhealing and burn wounds. Four types of gauzes were examined for the effect of the algino-cellulose finish on cotton gauze absorbency and elasticity. Fourier transform infrared (FTIR) spectroscopy of the film and alginate-citrate finished cotton showed formation of the alginate and citrate cellulose esters. Scanning electron microscopy analysis revealed large areas of the yarn surface covered by the alginate film with a smooth surface on the original fibers. Wetting of the gauze surface resulted in formation of a hydrated gel on the yarns with apparent swelling of the film and the fiber-coated alginate.

Alginates↗

A novel covalently crosslinked gel of alginate and silane with the ability to form bone-like apatite.

Hybrids consisting of bone-like apatite and biodegradable polymers are attractive materials for bone repair. We have shown that an alginate gel crosslinked covalently with ethylenediamine (EDA) enhances the repair of skin and nerves. In this study, we report a novel method for fabrication of an apatite-alginate nanohybrid using a simulated body fluid (SBF). Alginate was reacted with 3-aminopropyltriethoxysilane (APES), which gives silanol groups after hydrolysis, and/or EDA, by dehydration condensation using water-soluble carbodiimide to form gels. Modification of alginate with APES alone also gave a gel, because the alginate could be crosslinked by dehydration of silanol groups derived from APES. The gels obtained were soaked in a 1 mol/L CaCl2 solution and subsequently soaked in SBF. Apatite was formed on and inside the alginate gels modified with APES, whereas it was not formed on the gels without APES. Modification of alginate with silanol groups induced not only gel formation but also the apatite-forming ability on and inside the alginate gel in SBF. Consequently, a hydroxyapatite-alginate hybrid can be produced by modification of alginate with silanol groups and subsequent soaking in CaCl2 solution and SBF. Such a material is expected to be useful in bone repair.

Alginates↗

Calcium alginate beads as a slow-release system for delivering angiogenic molecules in vivo and in vitro.

A method previously used in this laboratory for entrapment of tumor cells in alginate beads has been extended to provide a slow release delivery system for growth factors with known in vivo angiogenic activity. Protein growth factors were entrapped in alginate beads in amounts sufficient to cause incorporation of 3H-thymidine by COMMA-D cells in vitro, and in vivo neovascularization when injected subcutaneously into Balb/c mice. Entrapment of 125I-labelled growth factors showed that the amount of molecule entrapped in alginate beads may vary with the charge of the molecule. In vitro cell proliferation studies showed that entrapment in alginate beads may provide a slow-release system or a stabilizing environment for the protein. In some cases biological activity of the growth factor in solution was increased by the presence of control alginate beads. When alginate-entrapped growth factors were injected into Balb/c mice, induction of new blood vessels could be monitored qualitatively by macroscopic photography and assessed quantitatively by measuring the pooling of radiolabelled red blood cells at the experimental site. Subcutaneous injection of purified angiogenic factors not entrapped in alginate beads did not cause neovascularization. Diffusion of 125I-labelled growth factors from alginate beads in the animal showed that release in vivo may depend on the charge of the protein molecule. These results indicate that injection of purified molecules entrapped in alginate beads provides an effective localized and slow-release delivery of biologically active molecules. This delivery system may extend the time of effectiveness of biologically active molecules in vivo compared to direct injection without alginate entrapment. The method of entrapment and injection has potential for identifying active factors in tumor-induced angiogenesis and testing new compounds as modulators of neovascularization.

Alginates↗

Peripheral nerve regeneration through alginate gel: analysis of early outgrowth and late increase in diameter of regenerating axons.

Our previous study revealed that alginate gel cross-linked with covalent bonds promoted peripheral nerve regeneration in the cat and rat. The present study analyzed nerve regeneration through alginate gel in the early stages within 2 weeks and the late stages up to 21 months after implantation. Four days after surgery, regenerating axons grew without Schwann cell investment through the partially degraded alginate gel, being in direct contact with the alginate without a basal lamina covering. Numerous mast cells infiltrated into the alginate. One to 2 weeks after surgery, regenerating axons were surrounded by common Schwann cells to form small bundles, with some axons at the periphery being partly in direct contact with alginate. At the distal stump, numerous Schwann cells had migrated into the alginate 8-14 days after surgery. They had no basal laminae. The diameter of regenerated myelinated fibers was small (approximately 1 micro m) at 8 weeks, but increased in diameter, having a distribution pattern similar to that of normal nerve 21 months after surgery. Much better nerve regeneration was found in alginate gel-, than collagen sponge-, and fibrin glue-implanted distal stump 12 months after surgery. These results indicate that alginate gel has good biocompatibility for regenerating axon outgrowth and Schwann cell migration, and that regenerated fibers can have a diameter as thick as that of normal fibers in the long term. Alginate gel is a promising material for use as an implant for peripheral nerve regeneration.

Alginates↗

Amitogenic alginates: key to first clinical application of microencapsulation technology.

Microencapsulation refers to a technique of immunoisolation by coating single cells or tissue with a semipermeable membrane. By combining microencapsulation with a specific tissue culturing method, iso-, allo-, and xenotransplantation of parathyroid tissue has been achieved without immunosuppression in a long-term animal model. Prior to its clinical use, continued analyses of the alginate, used as a coating substance, determined its mitogenic properties. Purification of the commercially available alginate was achieved using patented electrophoretic procedures, resulting in an amitogenic alginate suitable for use in humans. However, this alginate exhibited entirely different physical properties. We have recently shown that isotransplanted parathyroid tissue remains vital and functioning in vivo over long periods of time using the novel amitogenic alginate. It is essential to document, whether the alginate is able to maintain immunoisolation. We have therefore assessed its in vivo function compared to the mitogenic alginate in a transgenic animal model. Altogether 600 parathyroid glands from 300 Lewis rats (donor animals) were excised and subjected to tissue culture. Thereafter they were allotransplanted to 30 parathyroidectomized Dark-Auita rats, microencapsulated with the amitogenic or the mitogenic alginate or naked, with 10 recipient animals in each group. Total serum calcium and parathyroid hormone levels were monitored continuously at weekly intervals for 30 weeks. After 26 weeks the transplant beds were excised and subjected to histologic examination. More than 6 months after allotransplantation 9 of 10 animals that had received amitogenic transplants, compared to 7 of 10 animals in the group with mitogenic microcapsules were normocalcemic. Animals that had received naked parathyroid tissue were hypocalcemic as soon as 2 weeks after allotransplantation. Correspondingly, normocalcemic animals showed vital parathyroid tissue inside the microcapsules, which were surrounded by a significantly smaller rim of fibroblasts when amitogenic alginate had been used. In addition to confirming physiologic long-term function, we were able to document for the first time that immunoisolation can also be achieved with the novel amitogenic alginate, which is suitable for clinical use.

Alginates↗

Rheological studies of the interaction of mucins with alginate and polyacrylate.

The associative interaction of purified ovine and porcine submaxillary mucins (OSM and PSM) with sodium alginate was evaluated by comparing the rheological properties of mixtures against those of pure alginate and mucin in dilute, semi-dilute, and concentrated solutions. These systems were investigated as models for the interaction of mucin with the extracellular alginate produced by Pseudomonas aeruginosa. In dilute solution, evidence for such interaction cannot be obtained because aggregate species exist both in the OSM-alginate mixtures as well as in pure OSM. However, in the semi-dilute regime, mixtures containing a higher proportion of mucin show systematically higher viscosities than those predicted by simple additivity. In concentrated solutions containing higher proportions of mucin, an enhanced elastic response is observed. These results demonstrate a substantial binding interaction of mucins with alginate. This property is not observed in mixtures containing a high proportion of alginate, suggesting that mucins possess relatively low numbers of interacting sites. Introduction of 3 mM Ca2+ ions to all mucin-alginate mixtures enhances the elasticity due to gelation of alginate. Finally, comparison of the rheological properties of PSM-alginate mixtures with those of PSM-polyacrylate mixtures indicates that the binding strength of alginate to mucin is significantly weaker than that of polyacrylate.

Acrylic Resins↗

Preparation and characterization of superparamagnetic iron oxide nanoparticles stabilized by alginate.

SPION with appropriate surface chemistry have been widely used experimentally for numerous in vivo applications. In this study, SPION stabilized by alginate (SPION-alginate) were prepared by a modified coprecipitation method. The structure, size, morphology, magnetic property and relaxivity of the SPION-alginate were characterized systematically by means of XRD, TEM, ESEM, AFM, DLS, SQUID magnetometer and MRI, respectively, and the interaction between alginate and iron oxide (Fe(3)O(4)) was characterized by FT-IR and AFM. The results revealed that typical iron oxide nanoparticles were Fe(3)O(4) with a core diameter of 5-10 nm and SPION-alginate had a hydrodynamic diameter of 193.8-483.2 nm. From the magnetization curve, the Ms of a suspension of SPION-alginate was 40 emu/g, corresponding to 73% of that of solid SPION-alginate. This high Ms may be due to the binding of Fe(3)O(4) nanoparticles to alginate macromolecule strands as visually confirmed by AFM. SPION-alginate of several hundred nanometers was stable in size for 12 months at 4 degrees C. Moreover, T1 relaxivity and T2 relaxivity of SPION-alginate in saline (1.5 T, 20 degrees C) were 7.86+/-0.20 s(-1) mM(-1) and 281.2+/-26.4 s(-1) mM(-1), respectively.

Alginates↗

Biocompatibility of mannuronic acid-rich alginates.

Highly purified algin preparations free of adverse contaminants with endotoxins and other mitogens recently became available by a new purification process (Klöck et al., Appl. Microbiol. Biotechnol., 1994, 40, 638-643). An advantage of this purification protocol is that it can be applied to alginates with various ratios of mannuronic acid to guluronic acid. High mannuronic acid alginate capsules are of particular practical interest for cell transplantation and for biohybrid organs, because mannuronate-rich alginates are usually less viscous, allowing one to make gels with a higher alginate content. This will increase their stability and reduce the diffusion permeability and could therefore protect immobilized cells more efficiently against the host immune system. Here we report the biocompatibility of purified, mannuronic acid-rich alginate (68% mannuronate residues) in a series of in vitro, as well as in vivo, assays. In contrast to raw alginate extracts, the purified product showed no mitogenic activity towards murine lymphocytes in vitro. Its endotoxin content was reduced to the level of the solvent. Animal studies with these new, purified algin formulations revealed the absence of a mitogen-induced foreign body reaction, even when the purified material (after cross-linking with Ba2+ ions) is implanted into animal models with elevated macrophage activity (diabetes-prone BB/OK rat). Thus, alginate capsules with high mannuronic acid content become available for applications such as implantation. In addition to the utilization as implantable cell reactors in therapy and biotechnology, these purified algins have broad application potential as ocular fillings, tissue replacements, microencapsulated growth factors and/or interleukins or slow-release dosage forms of antibodies, surface coatings of sensors and other invasive medical devices, and in encapsulation of genetically engineered cells for gene therapy.

Alginates↗

Design of controlled-release solid dosage forms of alginate and chitosan using microwave.

The influence of microwave irradiation on the drug release properties of alginate, alginate-chitosan and chitosan beads was investigated. The beads were prepared with the highest possible concentration of polymer by an extrusion method. Sulphathiazole was selected as a model drug. The beads were subjected to microwave irradiation at various combinations of irradiation power and time. The profiles of drug dissolution, drug content, drug stability, drug polymorphism, drug-polymer interaction, polymer crosslinkage and complexation were determined by dissolution testing, drug content assay, differential scanning calorimetry (DSC) and fourier transform infra-red spectroscopy (FTIR). The chemical stability of the drug entrapped in the beads was unaffected by the microwave irradiation. However, the drug in the chitosan beads underwent polymorphic changes. Polymorphic changes were prevented by means of drug-alginate interaction in alginate and alginate-chitosan beads. Changes in the polymorphic state of drug were found to have insignificant effect on the drug release profiles of chitosan beads. The release-retarding property of alginate and alginate-chitosan beads was significantly enhanced by subjecting the beads to microwave irradiation. Positively charged calcium ions and chitosan are known to interact with negatively charged alginate. DSC and FTIR analyses indicated that the reduction in rate and extent of drug released from the treated beads was primarily due to additional formation of non-ionic bonds, involving alginate crosslinkage and alginate-chitosan complexation. The results showed that microwave technology can be employed in the design of solid dosage forms for controlled-release application without the use of noxious chemical agents.

Alginates↗

Synthesis and characterization of a pyrrole-alginate conjugate and its application in a biosensor construction.

N-(3-Aminopropyl)pyrrole was covalently coupled with alginate in an aqueous-phase reaction by means of carbodiimide-mediated activation chemistry to provide a pyrrole-alginate conjugate for subsequent use in biosensor applications. The pyrrole-alginate conjugate was quantified by UV spectroscopy at 230 nm, by an HPSEC-MALLS analytical method, as well as by FTIR and 13C NMR spectroscopies. The new pyrrole-alginate conjugate was used for the immobilization of polyphenol oxidase (PPO) onto an electrode surface by physical entrapment resulting from the gellification process and electrochemical polymerization of the pyrrole groups. The efficiency of this cross-linking approach (chemical and electrochemical) was investigated by comparing the amount of enzyme released from polypyrrole-alginate and regular alginate. In addition, biosensors were prepared by entrapment of the PPO in polypyrrole-alginate and regular alginate matrixes and their performance for the amperometric determination of catechol chosen as a model analyte was examined, yielding a sensitivity of 350 and 80 microA M(-1) cm(-2), respectively, for polypyrrole-alginate and alginate biosensors.

Alginates↗

Compaction properties of composite particles consisting of lactose with sodium alginate prepared by spray-drying.

PURPOSE: Composite particles of lactose with a small amount of sodium alginate were prepared by spray-drying (SD) in an effort to improve the compactibility of the polymer for direct compression. The compaction behavior of the SD composite particles with a range of polymer contents was investigated. METHODS: Composite particles were prepared by spray-drying an aqueous solution of lactose and sodium alginate at various formulating ratios. Improvement in the compactibility of the composite particles was evaluated by measuring the tablet tensile strength, porosity-applied pressure profiles, stress relaxation, elastic recovery of the compressed powder, and surface properties of the tablets by scanning electron microscopy. RESULTS: The tensile strength of compacts formed from the SD composite particles containing sodium alginate (< or = 10 wt%) was as high as that of spray-dried amorphous lactose. The improved compaction was attributed to the higher relaxation pressure and lower elastic recovery of the composite particles compared with alpha-lactose monohydrate. However, increasing the sodium alginate content of the SD composite particles above 10 wt% led to a marked reduction in the tensile strength of the resultant tablets. Scanning electron micrographs revealed that composite particles with a good compactibility fused totally in the tablets while composite particles containing 15% or more sodium alginate retained their shape, even after compression. The presence of sodium alginate layered uniformly on the surface of the particles and the increase in the glass transition temperature of the particles, possibly due to interpolation of sodium alginate are responsible for the reduction in the fusion property of the composite particles on compression. CONCLUSIONS: Although increasing the sodium alginate content of SD composite particles led to an increase in their plastic deformation, fusion on compression was prevented by the presence of sodium alginate. The reduced compactibility of SD composite particles with an excess amount of sodium alginate was attributed to reduced cohesion and fusion of the particles during compression.

Alginates↗

Involvement of the exopolysaccharide alginate in the virulence and epiphytic fitness of Pseudomonas syringae pv. syringae.

Alginate, a co-polymer of O-acetylated beta-1,4-linked D-mannuronic acid and L-guluronic acid, has been reported to function in the virulence of Pseudomonas syringae, although genetic studies to test this hypothesis have not been undertaken previously. In the present study, we used a genetic approach to evaluate the role of alginate in the pathogenicity of P. syringae pv. syringae 3525, which causes bacterial brown spot on beans. Alginate biosynthesis in strain 3525 was disrupted by recombining Tn5 into algL, which encodes alginate lyase, resulting in 3525.L. Alginate production in 3525.L was restored by the introduction of pSK2 or pAD4033, which contain the alginate biosynthetic gene cluster from P. syringae pv. syringae FF5 or the algA gene from P. aeruginosa respectively. The role of alginate in the epiphytic fitness of strain 3525 was assessed by monitoring the populations of 3525 and 3525.L on tomato, which is not a host for this pathogen. The mutant 3525.L was significantly impaired in its ability to colonize tomato leaves compared with 3525, indicating that alginate functions in the survival of strain 3525 on leaf surfaces. The contribution of alginate to the virulence of strain 3525 was evaluated by comparing the population dynamics and symptom development of 3525 and 3525.L in bean leaves. Although 3525. L retained the ability to form lesions on bean leaves, symptoms were less severe, and the population was significantly reduced in comparison with 3525. These results indicate that alginate contributes to the virulence of P. syringae pv. syringae 3525, perhaps by facilitating colonization or dissemination of the bacterium in planta.

Adaptation, Biological↗