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Influence of alginate characteristics on the properties of multi-component microcapsules.

A variety of sodium alginates, differing in molar mass and structural composition, have been evaluated in the preparation of multi-component microbeads and microcapsules. Bead formation occurred by gelation with calcium chloride. Capsules were produced by reacting the pre-formed beads with the oligocation poly(methylene-co-guanidine). Despite the equiponderous (1:1) mixing with a second polyanion, sodium cellulose sulphate, the influence of the alginate properties remains evident. Specifically, the effect of the chemical composition was found to be more significant than that of the molar mass for both the mechanical and transport properties. Furthermore, for alginates of 73% alpha-l-guluronic acid content less shrinking was observed compared to the 38% guluronic materials. This results in the case of the same encapsulator settings in larger microsphere diameters and thicker membranes accompanied by enhanced mechanical resistance though, also, in a higher permeability for the high-G capsules. However, subsequent coating with lower molar mass alginate allows one to adjust the permeability over a broad range, suitable for cell encapsulation and immunoprotection, without compromising the durability.

Alginates↗

Chitosan-coated alginate microspheres for embolization and/or chemoembolization: in vivo studies.

In this study, chitosan-coated alginate microspheres were prepared by the ionic complexation of alginate and chitosan biopolymers to use in embolization and/or chemoembolization studies. Biopolymeric microspheres were prepared by the ionic gelation technique of alginate with a suitable divalent cation (i.e. CaCl2) in a suspension medium composed of mineral oil and petroleum ether including emulsifier (i.e. Tween-80) and then obtained microspheres were coated with chitosan in an aqueous chitosan solution while the medium was magnetically stirred. The obtained microspheres are in the size range of 100-400 microm and they can be prepared as required by changing the preparation conditions (i.e. stirring rate, concentration of biopolymers, molecular weight and concentration of chitosan, etc.). In the in vivo studies, New Zealand rabbits were used as the test animals. Both complete and partial embolization of the kidney were achieved by using the microspheres. The renal angiograms obtained before/after embolization and the histopathological observations showed the feasibility of the chitosan-coated alginate microspheres as an alternative embolization and/or chemoembolization agent.

Alginates↗

Release characteristics of brilliant blue from calcium-alginate beads coated with quaternized chitosan.

Calcium-alginate beads coated with quaternized chitosan were prepared in a neutral environment, and morphologies were observed by SEM. Optimum conditions for the encapsulation and retention of a model drug (brilliant blue, BB) in acid were obtained from studies of preparation conditions, including alginate and quaternized chitosan concentration, calcium chloride (CaCl2) concentration in the gelling medium and by comparing one-step and two-step preparation methods. Results showed that very high BB encapsulation efficiency (99%, w/w) and low leakage in acid (8%, w/w) was achieved from dry beads when 2.0% (w/v) alginate was dropped into 1.0% (w/v) CaCl2 containing 0.3% (w/v) quaternized chitosan by a one-step method. The release of BB in 0.9% (w/v) NaCl was modulated by coating calcium-alginate with different weight average molecule weight (Mw) and degree of substitution (DS) of quaternized chitosan. A decreased of Mw accelerated the release of BB and a high DS value significantly decreased the release in 0.9% (w/v) NaCl.

Administration, Oral↗

Alginate as a source of dietary fiber.

Alginate, an algal polysaccharide, is widely used in the food industry as a stabilizer, or as a thickening or emulsifying agent. As an indigestible polysaccharide, alginate may also be viewed as a source of dietary fiber. Previous work has suggested that dietary fibres may protect against the onset and continuation of a number of cardiovascular and gastrointestinal diseases. This article aims to examine what is currently understood about the fiber-like activities of alginate, particularly its effects on intestinal absorption and the colon, and therefore aims to gauge the potential use of alginate as a dietary supplement for the maintenance of normal health, or the alleviation of certain cardiovascular or gastrointestinal diseases.

Alginates↗

Encapsulation of insulin in chitosan-coated alginate beads: oral therapeutic peptide delivery.

Insulin was encapsulated in calcium alginate beads coated with chitosan. Its release from alginate-chitosan and alginate-chitosan-glutaraldehyde beads was studied in artificial gastric (pH 1.2) and intestinal (pH 7.5) fluids. By comparing the release amounts, the ionic interaction between alginate-chitosan matrix with the medium pH's, intestinal fluid was found to be the better. The degradation of released insulin was also searched, even after 6 h incubation, the beads remained stable and the undegraded insulin seemed to be sufficient for the physiological conditions. Consequently, it can be said that the system can be offered for oral delivery of the therapeutic peptide drug insulin.

Administration, Oral↗

Spongelike alginate nanoparticles as a new potential system for the delivery of antisense oligonucleotides.

The aim of this study was to design a new antisense oligonucleotide (ON) carrier system based on alginate nanoparticles and to investigate its ability to protect ON from degradation in the presence of serum. Pharmacokinetics and tissue distribution of ON-loaded nanoparticles have been determined after intravenous administration. An original and dynamic process for ON loading into polymeric nanoparticles has been applied. It is based on the diffusion of ON or ON/polylysine complex into the nanoparticle or the alginate gel, respectively. Indeed, the single coincubation of ON with nanoparticles led, within a few days, to an extremely efficient association. The diffusion kinetic of ON was shown to be dependent on several parameters, incubation temperature, ON concentration, presence or absence of polylysine, polylysine molecular weight, and nanoparticle preparation procedure. This new alginate-based system was found to be able to protect [33P]-radiolabeled ON from degradation in bovine serum medium and to modify their biodistribution, as an important accumulation of radioactivity was observed in the lungs, in the liver, and in the spleen after intravenous administration into mice. ON may be associated efficiently with calcium alginate in a colloidal state. Such nanosponges are promising carriers for specific delivery of ON to lungs, liver, and spleen.

Alginates↗

The diffusion of beta-lactam antibiotics through mixed gels of cystic fibrosis-derived mucin and Pseudomonas aeruginosa alginate.

The rates of diffusion through purified extracellular alginate from Pseudomonas aeruginosa were measured for twelve beta-lactam antibiotics. The diffusion rate was reduced as the antibiotic molecular weight increased, but the range of diffusion rates exhibited by a common anti-pseudomonal penicillins was relatively small. The diffusion of ticarcillin through 1.0% w/v mixtures of alginate and purified mucus glycoprotein (mucin) from sputa of cystic fibrosis patients showed that, at equivalent concentrations, alginate represented the greater barrier to penetration. However if the mucin concentration was increased to 4.0% w/v, a more realistic physiological concentration, the diffusion of ticarcillin was retarded to a greater extent than in 1% w/v alginate, and the effect was compounded by other sputum components such as DNA. The results suggest that the antibiotic diffusion barrier represented by mucin may be significant in vitro, particularly for nebulized antibiotics.

Alginates↗

A small dose of soluble alginate-fiber affects postprandial glycemia and gastric emptying in humans with diabetes.

Seven men with well-controlled, noninsulin-dependent (type 2) diabetes ingested on two different mornings, in random order, meals with or without a 5.0-g sodium alginate supplement (algae-isolate, 75% soluble fiber). The meals contained similar amounts of digestible carbohydrates, fat and protein. The gastric emptying rate of the meal containing sodium alginate, measured by detection of 51Cr mixed into the meals, was significantly slower than that of the fiber-free meal. Sodium alginate also induced significantly lower postprandial rises in blood glucose, serum insulin and plasma C-peptide. The diminished glucose response after the addition of sodium alginate could be correlated to the delayed gastric emptying rate induced by the fiber (rs = 0.92, P less than 0.01).

Adult↗

Strontium biokinetics in humans: influence of alginate on the uptake of ingested strontium.

Radioactive isotopes of strontium, mainly 90Sr, released into the environment due to nuclear accidents may contribute significantly to the internal radiation exposure of members of the public after ingestion of strontium with contaminated foodstuffs. The committed radiation dose is significantly dependent on the fraction of the ingested activity that crossed the gut wall (f1 value). In tracer kinetic investigations, the effect of sodium alginate on the gastrointestinal absorption of strontium was studied in human subjects. Sodium alginate was proven to be a potent agent for reducing strontium absorption with high efficiency and virtually no toxicity. The data obtained show that the uptake of ingested strontium from milk was reduced by a factor of nine when alginate was added to milk. It is concluded that alginate preparations are a suitable antidote against radiostrontium.

Administration, Oral↗

Xenotransplantation of porcine and bovine islets without immunosuppression using uncoated alginate microspheres.

Uncoated spherical hydrogel microspheres (calcium alginate, nominal M(r) exclusion of > 600 kD) 800-900 microns in diameter were employed to prevent immune rejection of discordant islet xenografts isolated from pigs and cows. The islets were immobilized in the microspheres and injected into the peritoneum of 14 nonimmunosuppressed streptozotocin (STZ)-induced diabetic C57BL/6J mice. Four recipients received islet grafts from bovine calves, and 10 received islet grafts from pigs. In the control group of 15 diabetic mice implanted with nonencapsulated islets, 6 received i.p. porcine islets and 5 received i.p. bovine islets, whereas remaining 4 received porcine islets under the kidney capsule. Plasma glucose concentrations in recipients of the alginate-encapsulated islets promptly dropped from a preimplantation value of 498 +/- 47 (mean +/- SEM) to 142 +/- 6 (bovine) and 178 +/- 7 mg/dl (porcine) during the first wk. All the animals sustained these levels for at least 1 mo. Two mice implanted with bovine islets subsequently reverted to diabetes (plasma glucose > 250 mg/dl) at 43 days postimplantation. The remaining grafts maintained function for > 10 wk. In contrast, nonencapsulated islets failed to function, or sustained euglycemia for < 4 days. Mice receiving encapsulated islets showed a 23-38% gain in body weight during the first mo after implantation, compared with < 1% (P < 0.002) and 32% (P = 0.84) for the untreated diabetic (n = 6) and normal control (n = 6) groups. Immunohistochemical staining of long-term grafts (> 10 wk) revealed viable islets, with well-granulated alpha, beta, and delta cells; the external surfaces of the microreactors were free of fibrotic overgrowth and exhibited only occasional host cell adherence. Uptake studies with IgG and thyroglobulin (M(r) of 669 kD) suggest that the microreactors were permeable to molecules with a molecular weight of up to > 600 kD (including the various proteins of the complement system, M(r) of 24-570 kD). Spheres implanted in the peritoneum after only 1 wk stained positive for both IgG and for the C3 component of complement. These findings suggest that prolonged survival of discordant xenografts of porcine and bovine islets in the STZ diabetic mouse model can be achieved with uncoated alginate microspheres that are permeable to IgG and complement. The question of whether similar results can be achieved with uncoated alginate microspheres in higher animals remains to be fully determined.

Alginates↗

Alginate production affects Pseudomonas aeruginosa biofilm development and architecture, but is not essential for biofilm formation.

Extracellular polymers can facilitate the non-specific attachment of bacteria to surfaces and hold together developing biofilms. This study was undertaken to qualitatively and quantitatively compare the architecture of biofilms produced by Pseudomonas aeruginosa strain PAO1 and its alginate-overproducing (mucA22) and alginate-defective (algD) variants in order to discern the role of alginate in biofilm formation. These strains, PAO1, Alg+ PAOmucA22 and Alg- PAOalgD, tagged with green fluorescent protein, were grown in a continuous flow cell system to characterize the developmental cycles of their biofilm formation using confocal laser scanning microscopy. Biofilm Image Processing (BIP) and Community Statistics (COMSTAT) software programs were used to provide quantitative measurements of the two-dimensional biofilm images. All three strains formed distinguishable biofilm architectures, indicating that the production of alginate is not critical for biofilm formation. Observation over a period of 5 days indicated a three-stage development pattern consisting of initiation, establishment and maturation. Furthermore, this study showed that phenotypically distinguishable biofilms can be quantitatively differentiated.

Alginates↗

Crystallization and preliminary X-ray analysis of alginate lyases A1-II and A1-II' from Sphingomonas sp. A1.

Alginate lyases depolymerize alginate, a heteropolysaccharide consisting of alpha-L-guluronate and beta-D-mannuronate, through a beta-elimination reaction. The alginate lyases A1-II (25 kDa) and A1-II' (25 kDa) from Sphingomonas sp. A1, which belong to polysaccharide lyase family PL-7, exhibit 68% homology in primary structure but have different substrate specificities. To determine clearly the structural basis for substrate recognition in the depolymerization mechanism by alginate lyases, both proteins were crystallized at 293 K using the vapour-diffusion method. A crystal of A1-II belonged to space group P2(1) and diffracted to 2.2 A resolution, with unit-cell parameters a = 51.3, b = 30.1, c = 101.6 A, beta = 100.2 degrees, while a crystal of A1-II' belonged to space group P2(1)2(1)2(1) and diffracted to 1.0 A resolution, with unit-cell parameters a = 34.6, b = 68.5, c = 80.3 A.

Alginates↗

Alginates. A "new" dressing alternative.

BACKGROUND: Currently, a wide variety of bio-occlusive dressing materials are available. In general, these dressing materials provide a moist wound healing environment that has been shown to promote healing in both human and animal studies. To effectively use these dressings the clinician must have a full understanding of the properties of the materials as well as the pathophysiology of the particular wound. Most recently, a "new" biosynthetic dressing material, the alginates, has become available. OBJECTIVE: To highlight proper use of alginate dressings for the management of acute and chronic wounds. METHODS: Case study and literature review. RESULTS: Alginates were shown to be effective in a wide variety of acute and chronic wounds. CONCLUSION: Alginates possess several unique properties that should prove useful to the dermatologic surgeon as well as the dermatologist. Proper patient selection and use of this "new" dressing material, as well as a review of the literature is presented.

Alginates↗

Production of alginate beads by emulsification/internal gelation.

Alginate microspheres were produced by emulsification/internal gelation of an alginate sol dispersed within vegetable oil, followed by a reduction in pH to release calcium from an insoluble salt. Microspheres with mean diameters ranging from 50 to 1,000 microm were obtained with standard deviations ranging from 35 to 45% of their mean value. Smooth, spherical beads were obtained with the narrowest size dispersion when using low guluronic and low viscosity alginate and a carbonate complex as calcium vector. The calcium salt must also be included within the alginate sol as a very fine powder to promote homogeneous gelation. Internal gelation was also tested with the dropping method. Observation of the beads produced revealed that the structure of the beads is more homogeneous than observed with external gelation. Shrinking is more important, although the diffusion of large molecules is faster with internal versus external gelation.

Alginates↗

The comparative bioavailability of cimetidine-alginate treatments.

The comparative bioavailability of cimetidine in cimetidine-alginate combinations has been investigated in twelve healthy volunteers in an open crossover study. Each volunteer received a single oral dose of a commercially available alginate-cimetidine combination tablet (Algitec) or cimetidine tablets (Tagamet), co-administered with a commercially available alginate reflux suppressant liquid or tablet (Gaviscon). No significant differences were observed between treatments for Cmax, tmax, AUC0-12 or AUC0- infinity. The study demonstrated equivalent bioavailability of cimetidine when administered separately with alginate products and as a fixed dose combination product.

Administration, Oral↗

Host reaction against empty alginate-polylysine microcapsules. Influence of preparation procedure.

Microcapsules, prepared with alginate and polylysine, were injected intraperitoneally into mice and the number of peritoneal leucocytes as well as the cells sticking to the capsule wall were counted after 4-28 days. A significant increase in host reaction was observed when the microcapsules contained an outer layer of polylysine as compared with calcium alginate beads without polylysine or microcapsules coated with an outer layer of alginate. The alginate sources influenced the host reaction significantly. After an intraperitoneal residence of 4 days, the microcapsules were mainly surrounded by macrophages. After 28 days, several cell layers surrounded the microcapsules; macrophages, multinucleate giant cells, fibroblasts and mesothelial cells.

Alginates↗

Inhibition of tobramycin diffusion by binding to alginate.

[3H]tobramycin bound to sodium alginate and to exopolysaccharide prepared from two mucoid strains of Pseudomonas aeruginosa. Binding to sodium alginate was similar to binding to exopolysaccharide, both in the dependence on tobramycin concentration and in the maximum binding observed at saturation. Incorporation of sodium alginate into agar plates reduced the zone sizes of growth inhibition caused by tobramycin. The reductions in zone sizes were quantitatively accounted for by the binding of tobramycin to sodium alginate during diffusion of the antibiotic away from the well in which it had been placed at the start of the experiment. However, the binding of tobramycin to the exopolysaccharide of P. aeruginosa, and the resulting inhibition of diffusion of the antibiotic, did not significantly increase the penetration time of a spherical microcolony with a radius of 125 micron, such as might be found in the respiratory tract of a patient with cystic fibrosis (from a 90% penetration time of 12 s in the absence of exopolysaccharide to one of 35 s with an exopolysaccharide concentration of 1.0% [wt/vol]).

Alginates↗

Alginate lyase promotes diffusion of aminoglycosides through the extracellular polysaccharide of mucoid Pseudomonas aeruginosa.

We demonstrated that a 2% suspension of Pseudomonas aeruginosa alginate completely blocked the diffusion of gentamicin and tobramycin, but not that of carbenicillin, illustrating how alginate production can help protect P. aeruginosa growing within alginate microcolonies in patients with cystic fibrosis (CF) from the effects of aminoglycosides. This aminoglycoside diffusion barrier was degraded with a semipurified preparation of P. aeruginosa alginate lyase, suggesting that this enzyme deserves consideration as an adjunctive agent for CF patients colonized by mucoid strains of P. aeruginosa.

Alginates↗