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Foreign body reaction to calcium alginate fibre mimicking recurrent tumour of the submandibular salivary gland.

A 50-year-old woman was referred after the discovery of adenoid cystic carcinoma in an excised left submandibular gland. Treatment involved clearance of the left submandibular fossa, and bilateral levels II and III selective neck dissections. A left-sided submandibular haematoma developed during the immediate postoperative period. After removal of the clot, there was a persistent, low volume capillary ooze from the left submandibular fossa and a calcium alginate fibre pack (Kaltostat) was left in place to control the bleeding. After an extended period of time the pack excited a foreign body reaction which, on a computed tomogram, mimicked a recurrence of the tumour. We review the role of Kaltostat in this setting and its potential for foreign body reaction, which may mimic serious disease.

Alginates↗

AlgR3, a protein resembling eukaryotic histone H1, regulates alginate synthesis in Pseudomonas aeruginosa.

A regulatory mutation (alg52) in a Pseudomonas aeruginosa alginate-negative mutant (strain 8882) is complemented efficiently by the gene algR2 and somewhat inefficiently by a second gene termed algR3. algR3 and algR2 are located on a 4.4-kilobase-pair HindIII-BamHI fragment, which has been completely sequenced. algR2 has previously been characterized. Introduction of kanamycin-resistance cassettes and deletion-subcloning experiments involving various open reading frames in the HindIII-BamHI fragment have localized the algR3 gene, which encodes a 340-amino acid polypeptide. This highly basic regulatory protein contains 17% lysine and 36% alanine. The predicted amino acid sequence shows no significant similarity with any bacterial proteins and yet is highly similar to the sea urchin Lytechinus pictus histone H1 subtype of protein. Promoter localization by reverse transcriptase mapping of the algR3 gene shows the presence of Escherichia coli sigma 70 recognition sequences, and coupled transcription/translation experiments in E. coli demonstrate the presence of a 39-kDa polypeptide encoded by the cloned algR3 gene.

Alginates↗

Comparative gastrointestinal and plasma cholesterol responses of rats fed on cholesterol-free diets supplemented with guar gum and sodium alginate.

The present study investigated the digestion and cholesterol-lowering effects of the water-soluble NSP guar gum (GG) and sodium alginate (SA) in laboratory animals. Groups of five male Wistar strain rats were fed semi-purified cholesterol-free diets containing 0, 50 or 100 g NSP source/kg for 21 d which comprised a 14-d adaptation period followed by a 7-d balance period. Weight gain over the balance period and food conversion ratio decreased linearly with increasing NSP intake ( and respectively). DM digestibility decreased with increasing NSP intake and this effect was greater for SA-containing diets compared with GG-containing diets At the lower inclusion rate, 0.9-1.0 of the additional NSP was digested, but this value fell to 0.8 for both NSP sources at the 100 g/kg inclusion rate, implying that the capacity for near complete digestion of the test NSP had been exceeded. Intestinal tissue mass was increased in response to inclusion of both NSP sources. Caecal digesta pH decreased linearly with additional GG, but increased slightly with consumption of SA. Total caecal short-chain fatty acid concentrations (micromol/g caecal contents) increased markedly with 50 g GG/kg but did not increase further with 100 g GG/kg, and were slightly lower than control values in rats consuming SA. Plasma cholesterol concentration fell linearly with increasing NSP in the diet and the effect was similar for both GG and SA. Total output of faecal bile acids rose in rats fed 50 g GG/kg and 50 g SA/kg (59 micromol/7 d v. 24 micromol/7 d for control rats) with no further increase at the higher inclusion rate. These results show that SA has a strong hypocholesterolaemic effect in rats which is similar to that of GG, and that this effect is most likely to be mediated through an interruption in the entero-hepatic circulation of bile acids and not through increased hepatic supply of propionate from fermentation of the NSP in the large bowel.

Alginates↗

Experimental maintenance of the schistosome vector Biomphalaria glabrata on an improved alginate gel.

An improved alginate formulation containing Spirulina algae or freeze-dried lettuce is described for experimental maintenance of Biomphalaria glabrata. Snail growth, food consumption and assimilation were higher on the gel containing Spirulina. The increased growth was not entirely the result of the higher food consumption observed with Spirulina, but appeared to be due to nutritional differences between the two nutrient sources. Snails responded to decreased dietary Spirulina concentration by increasing their relative level of assimilation rather than by increasing food consumption. An antibiotic treatment with chloramphenicol and ampicillin for the reduction of bacterial contaminants associated with B. glabrata is also described.

Alginates↗

Characterization of structure and diffusion behaviour of Ca-alginate beads prepared with external or internal calcium sources.

Ca-alginate beads were prepared with either external or internal calcium sources. The structures of both beads were investigated with the aid of scanning electron microscopy (SEM) and confocal microscopy. It was shown that the beads with internal calcium source had a looser structure and bigger pore size than those with external calcium source. The attempts to interpret the difference were carried out by determining the Ca content within the beads at various times, which indicated that it was the different gelation mechanisms that caused the difference of structures of both beads. Furthermore, it was also found that the diffusion rate of haemoglobin (Hb) within the beads with an internal calcium source was faster than that of the beads with an external one, which was consistent with the observation of their structures.

Alginates↗

Ionotropic alginate beads for controlled intestinal protein delivery: effect of chitosan and barium counter-ions on entrapment and release.

Alginate beads containing the model protein haemoglobin (Hb) were prepared by coagulation with various counter-ions to improve the controlled release of the protein. The effect of Ba(2+) and Ca(2+) ions and of the polycationic polysaccharide chitosan was investigated. Coagulation with Ba(2+), Ca(2+) and/or chitosan showed differences in the swelling index of the beads, in the encapsulation efficiency of Hb entrapment and in the release of the entrapped protein. Chitosan in the coagulation fluid markedly enhanced the encapsulation efficiency of the Hb. Release studies were conducted in simulated gastric fluid (SGF pH approximately or equal to 1.2) and subsequently in simulated intestinal fluid (SIF ) at 37 degrees C. Beads were stable in the gastric fluid but released their protein upon transfer to intestinal fluid. The release coincides with the burst and disintegration of beads. Rate of protein release from the beads was affected by the Ba(2+) and chitosan concentration in coagulation fluid.

Alginates↗

Calcium-alginate coated, whey protein-based microspheres: preparation, some properties and opportunities.

An 'all aqueous' encapsulation process followed by a heat treatment was used to prepare calcium-alginate-coated, whey protein-based, water insoluble microspheres containing micronized calcium carbonate as a model core. Results obtained with this process were compared to those obtained with a similar process in which chemical cross-linking was utilized. At an initial core load of 25 or 50% (w/w), core retention ranged from 84.2-95.12% and was not significantly affected by the initial core load or by the cross-linking method. Regardless of the cross-linking method, protein retention during the process was high and ranged from 78.2-87.5%. Outer topography of the microspheres was not influenced by the cross-linking method, however, at a given composition, the inner structure of heat treated microspheres differed from that obtained with chemically-cross-linked microspheres. Swelling properties of denovo microspheres were affected by pH. Results indicated that the micronized calcium carbonate could be used as a porogenic core. Removal of the core, by an acid treatment, allowed preparing microporous delivery devices. In addition to offer opportunities for encapsulation and delivery of crystalline core, the investigated process can provide means to prepare 'ghost' microporous delivery systems that can, in potential, be loaded, following their preparation, with sensitive core materials at conditions that favour the stability and functionality of this core.

Alginates↗

Viability analysis of alginate encapsulated micro-organisms using fluorescent stains.

The encapsulation of micro-organisms such as bacteria and fungi in biopolymers is currently being evaluated as delivery systems in many fields. Information about the viability and morphology of the organisms in the microparticle is often required to ascertain the longevity of the systems. A rapid method using fluorescent stains for microbial viability has been validated for organisms within alginate microparticles. Usually viability is assessed by dissolving the microparticles and cell culturing. This new method is advantageous for slow growing or filamentous organisms because these are not quickly or accurately enumerated by plate counts. In addition, the technique also allows the morphology of the organism to be monitored over time.

Alginates↗

Review and current status of emulsion/dispersion technology using an internal gelation process for the design of alginate particles.

Emulsification/internal gelation has been suggested as an alternative to extrusion/external gelation in the encapsulation of several compounds including sensitive biologicals such as protein drugs. Protein-loaded microparticles offer an inert environment within the matrix and encapsulation is conducted at room temperature in a media free of organic solvents. Recently, the concept of internal gelation has been applied to formulating nanoparticles as drug delivery systems. Emulsification/internal gelation technologies available for microparticles preparation, particularly that involving alginate polymer, are described as well as recent advances towards applications in nanotechnology. Those methods show great promise as a tool for the development of encapsulation processes, especially for the new field of nanotechnology using natural polymers.

Alginates↗

Polymers for sustained release formulations of dipyridamole-alginate microspheres and tabletted microspheres.

The preparation of dipyridamole (DIP) alginate (alg) microspheres by different methods or the incorporation of tragacanth (trgh), pectin or Eudragit L-100 55 (Eud) in alg microsphere formulations did not provide a prolonged release of DIP at pH 1.2. Tabletted microsphere formulations containing alg, trgh, pectin, sodium carboxymethyl cellulose (CMC), sodium starch glycolate (SSG), carrageenan (carrg) or Eud as diluents in different ratios, produced tablets with good physical properties which did prolong DIP release. The type, viscosity and the ratio of the diluent polymer, microsphere size and the compression pressure were found to be important factors to produce tablets with desired properties. No advantage of the tablets containing alg microspheres and granulated diluents was observed over the tablets containing powdered diluents.

Alginates↗

Alginate-based in situ gelling suspensions and emulsions comprising N4-alkyloxycarbonyl derivatives of cytosine: zero-order release and effect of physicochemical properties.

As an alternative to incorporation of various excipients, N(4)-alkyloxycarbonyl-cytosine derivatives possessing various physicochemical properties and cytosine regeneration rates have been examined to modify release rate and kinetics from in situ gelling alginate formulations, e.g., liquid formulations that gel in acidic gastric juice and release the entrapped derivative or parent cytosine. Linear relationships were obtained between the release rate constants and the square root of the solubility for suspension formulations. Calculated diffusion coefficients were observed to be similar for suspension and solution formulations; however, for in situ gelling emulsion formulations, diffusivity correlated linearly to log P. Zero-order release of parent cytosine was observed from in situ gelling suspensions of the poorly soluble acid-labile N(4)-adamantyloxycarbonyl-cytosine prodrug.

Acetamides↗

226Ra induced bone-cancers: the effects of a delayed Na-alginate treatment.

At the present time no unequivocal evidence exists which shows that a reduction in the body-burden of a radionuclide by decorporative treatment results in a proportional decrease in the risk of long-term radiation effects. We have investigated the effectiveness of the daily administration of Na-alginate via the diet in removing 226Ra from the skeleton and in reducing the number of late effects such as osteosarcomas. The animals used were male C57Bl mice which had been injected with one of three different amounts of 226Ra (4.4, 10.7 or 24.8 kBq) four days prior to the onset of the decorporative treatment. The results showed that although this treatment was able to produce a substantial reduction in the 226Ra content of the mice it did not reduce the incidence of osteosarcoma. These results question the effectiveness of decorporation procedures initiated at longer times after contamination.

Alginates↗

Ex-vivo evaluation of alginate microparticles for Polymyxin B oral administration.

A crosslinked alginate microparticle system for the targeting to the lymphatic system by Peyer's patches (PP) uptake was designed in order to improve the oral absorption of Polymyxin B (PMB). To verify mucoadhesion and PP uptake, microparticles labelled with fluorescein isothiocyanate (FITC) were prepared by spray-drying technique and crosslinking reactions with calcium ions and chitosan (CS), in vitro characterized and assayed by an ex vivo method. Microparticles showed a size less then 3 microm, an antibiotic loading level of 11.86 +/- 0.70%, w/w, a sustained drug release behaviour in simulated gastro-intestinal (GI) fluids and a preserved biological activity throughout the manufacture. The ex vivo study was performed by a perfusion method on intestinal tracts of just sacrificed adult rats. The recovered samples were analysed by epifluorescence microscope for mucoadhesion and PP uptake and by microbiological analysis for antibiotic activity preservation, providing evidence of mucoadhesion at the level of both PP and non-PP epithelium, uptake by PP and PMB microbiological activity in PP tissue. Furthermore, the study revealed the involvement of transport pathways across villous enterocytes.

Administration, Oral↗

In vitro release study of verapamil hydrochloride through sodium alginate interpenetrating monolithic membranes.

Polymeric sodium alginate interpenetrating network membranes containing verapamil hydrochloride were fabricated for transdermal application. The membranes were evaluated for their physical properties, weight and thickness uniformity, water vapor transmission, as well as drug content uniformity. All the thin patches were transparent, smooth, and flexible. The drug-loaded membranes were analyzed by X-ray diffraction to understand the drug polymorphism inside the membrane. The transdermal patches were permeable to water vapor, indicating the permeability characteristics of the polymers. The in vitro drug release was performed in distilled water using a Keshary-Chien diffusion cell. The release data were analyzed to understand the mechanism of drug release.

Alginates↗

Release of furosemide from multiple-unit and single-unit preparations containing different viscosity grades of sodium alginate.

The release characteristics and the effect of viscosity of sodium alginate on the release rate of furosemide (a rather poorly soluble drug) from hard gelatin capsules (single-unit), and minitablets (multiple-unit) filled in hard gelatin capsules, were evaluated. Swelling and erosion experiments showed a different behavior for each viscosity grade. Polymer characteristics influenced significantly the release of the drug from the preparations prepared and tested. The results indicate that erosion plays a significant role, accelerates release rate and shortens duration of drug release. Low viscosity formulations exhibited a greater erosion, and drug release was completed in 4 hours. Medium viscosity formulations showed intermediate erosion, while high viscosity formulations exhibited less erosion, and drug release was completed in 8 hours. The minitablets always displayed lower release and dissolution efficiency values than the capsules, and as the viscosity increased, the difference of dissolution efficiency between the two formulations increased accordingly. The results further indicated that the multiple-unit system demonstrated a more pronounced sustained effect than the single-unit, and therefore, it is a more suitable preparation for sustained release delivery of poorly soluble drugs. Analysis of release data indicate a rather zero-order release mechanism, which may be attributed mainly to swelling and an erosion/dissolution process.

Alginates↗

Chondrogenic potential of in vitro multiplied rabbit perichondrium cells cultured in alginate beads in defined medium.

Perichondrium has a chondrogenic capacity and is therefore a candidate tissue for engineering of cartilage in vitro. Donor age and culture conditions probably influence chondrogenesis. The aim of this study was to compare the chondrogenic capacity of ear and nasal perichondrium from young and adult rabbits, using serum containing and serum-free culture conditions. This study demonstrates that more than 1 million cells can be generated out of 1 cm(2) of perichondrium tissue in 3-5 weeks of culture, irrespective of age. Culturing of these cells in alginate in medium with 2, 10, or 20% fetal calf serum did result in the production of small amounts of glycosaminoglycan, but no collagen type II was demonstrated. When serum was replaced however by insulin-like growth factor-1 (IGF-1) (10 ng/mL) plus transforming growth factor-beta2 (TGF-beta2) (10 ng/mL) an increased glycosaminoglycan production and induction of collagen type II was found, especially in cells isolated from perichondrium of the ear. Cells derived from perichondrium of young rabbits showed larger chondrogenic potential than cells from perichondrium of adult rabbits. Moreover, stimulation of both glycosaminoglycan synthesis and collagen type II production was about five times higher in cells isolated from the ear perichondrium of young rabbits than of adult rabbits. We conclude that young auricular perichondrium seems a useful source of cells for tissue engineering of cartilage when cultured in serum-free medium in combination with IG-F1 and TGF-beta2.

Alginates↗

A novel use of alginate hydrogel as Schwann cell matrix.

The use of bioresorbable conduits supplemented with Schwann cells (SCs) is a promising tissue engineering technique to replace nerve grafting. Alginate hydrogel (AH), as a SC tissue engineering matrix, has many advantages over previously used matrices but has not been evaluated for this purpose. In this study, the viability and proliferation of SCs together with SC function in AH was evaluated in vitro. AlamarBlue cell assay was used to monitor the viability of SCs in AH and compared to SC viability in collagen gel, fibrin glue, hyaluronic acid, Matrigel, and standard culture plate over 5 days in culture. The results showed that the viability and growth of SCs in different matrices over the culture period did not significantly differ to culture plate culture. SC function when suspended in AH was monitored using chick embryo dorsal root ganglia (CDRG) growth assay. Growth of CDRG in AH with or without SCs was compared to CDRG growth without AH matrix. After 3 days in culture, the mean length of neurite sprouting was measured. The results showed that there was neurite growth in AH but was reduced to 43% of control. The neurite growth in AH was, however, enhanced by 170% when SCs were suspended in the gel. In conclusion, AH supported SC viability and function in vitro and may be useful in peripheral nerve tissue engineering in reconstructive procedures.

Alginates↗

Collagen fibrillogenesis by chondrocytes in alginate.

Collagen is the primary structural component in connective tissue. The poor mechanical properties of most cell-seeded cartilage grafts used for cartilage repair can be attributed to the low level of collagen synthesized compared with native cartilage. In this study, the synthesis and assembly of collagen by chondrocytes in hydrogels were investigated, with particular attention paid to the role of cross-link formation in this process. Primary bovine chondrocytes were seeded in alginate and collagen synthesis was assessed in the presence and absence of beta-aminopropronitrile (BAPN), a potent inhibitor of the enzyme lysyl oxidase and collagen cross-link formation. Cultures on days 21, 35, and 49 were evaluated by stereology, biochemistry, and real-time reverse transcriptase-polymerase chain reaction. All measures of collagen synthesis (except hydroxyproline) significantly increased in the presence of 0.25 mM BAPN. By 35 days of culture, the average collagen fibril diameter was 62 +/- 10 nm in control cultures and 109 +/- 20 nm with BAPN supplementation. The collagen volume density increased from 5 +/- 3% in control cultures to 17 +/- 1% in the presence of BAPN. Likewise, the expression of cartilage-specific collagens (type II and XI) and aggrecan increased significantly as a result of BAPN culture. These findings demonstrate the prominent role of collagen cross-linking in collagen fibrillogenesis and suggest approaches by which collagen synthesis and assembly could be controlled in tissue-engineered constructs.

Alginates↗