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PubMed2007

Development of a biodegradable alginate carrier system for antibiotics and bone cells.

This study presents a novel biodegradable alginate delivery system for antibiotics and bone cells to treat infected bone defects. About 2 x 10(7) New Zealand rabbit mesenchymal stem cells (MSCs) and 5 mL vancomycin solution (50 mg/mL) were added to 5 mL of 2.5% (w/v) sodium alginate solution to form biodegradable antibiotic and MSCs alginate beads 3 mm in diameter. The alginate beads were then cultured in an osteogenic medium for 14 days. The profiles of antibiotics released from the alginate beads were evaluated using the method of high performance liquid chromatography (HPLC). The expression of osteogenic genes, including Cbfa1 and osteopontin, in the alginate beads was determined by reverse transcription-polymerase chain reaction (RT-PCR) analysis. The alkaline phosphatase activity, calcium level, and mineral deposition of the cultured cells within the alginate beads were assessed. Analytical results demonstrated that the concentrations of vancomycin eluted from the alginate beads were, for 14 days, well above the minimal inhibitory concentration of Staphylococcus aureus. Osteopontin and mRNA of Cbfa1 were detected and increased alkaline phosphatase activity and calcium levels were noted, as was a substantial mineral deposition in cultured MSCs. The PKH 26-labeled MSCs and vancomycin alginate beads were implanted in rabbit bony cavities for in vivo analysis. Implanted PKH 26-labeled MSCs were identified in the newly formed bony trabeculae in all specimens at 2 and 4 months after implantation and there was abundant mineral deposition. The results of in vitro study demonstrated sustained elution of vancomycin from the alginate carrier for 14 days and good osteogenic differentiation of cultured MSCs in the alginate carrier matrix. The results of in vivo study demonstrated the implanted MSCs participating in new bone formation. Based on experimental evidence, development of a biodegradable alginate carrier system for antibiotics and bone cells is possible, providing a potential treatment procedure for infected bone defects.

Alginates↗

PubMed1998

Biphasic release characteristics of dual drug-loaded alginate beads.

The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into CaCl2 solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorly water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329 microns. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate beads, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing Eudragit polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with Eudragit RS100 polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of drug released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.

Alginates↗

PubMed2004

Enzyme immobilization in novel alginate-chitosan core-shell microcapsules.

Alginate-chitosan core-shell microcapsules were prepared in order to develop a biocompatible matrix for enzyme immobilization, where the protein is retained either in a liquid or solid core and the shell allows permeability control over substrates and products. The permeability coefficients of different molecular weight compounds (vitamin B2, vitamin B12, and myoglobin) were determined through sodium tripolyphosphate (Na-TPP)-crosslinked chitosan membrane. The microcapsule core was formed by crosslinking sodium alginate with either calcium or barium ions. The crosslinked alginate core was uniformly coated with a chitosan layer and crosslinked with Na-TPP. In the case of calcium alginate, the phosphate ions of Na-TPP were able to extract the calcium ions from alginate and liquefy the core. A model enzyme, beta-galactosidase, was immobilized in the alginate core and the catalytic activity was measured with o-nitrophenyl-beta-D-galactopyranoside (ONPG). Change in the activity of free and immobilized enzyme was determined at three different temperatures. Na-TPP crosslinked chitosan membranes were found to be permeable to solutes of up to 17,000Da molecular weight. The enzyme loading efficiency was higher in the barium alginate core (100%) as compared to the calcium alginate core (60%). The rate of ONPG conversion to o-nitrophenol was faster in the case of calcium alginate-chitosan microcapsules as compared to barium alginate-chitosan microcapsules. Barium alginate-chitosan microcapsules, however, did improve the stability of the enzyme at 37 degrees C relative to calcium alginate-chitosan microcapsules or free enzyme. This study illustrates a new method of enzyme immobilization for biotechnology applications using liquid or solid core and shell microcapsule technology.

Alginates↗

PubMed2000

Ionic and acid gel formation of epimerised alginates; the effect of AlgE4.

AlgE4 is a mannuronan C5 epimerase converting homopolymeric sequences of mannuronate residues in alginates into mannuronate/guluronate alternating sequences. Treating alginates of different biological origin with AlgE4 resulted in different amounts of alternating sequences. Both ionically cross-linked alginate gels as well as alginic acid gels were prepared from the epimerised alginates. Gelling kinetics and gel equilibrium properties were recorded and compared to results obtained with the original non-epimerised alginates. An observed reduced elasticity of the alginic acid gels following epimerisation by AlgE4 seems to be explained by the generally increased acid solubility of the alternating sequences. Ionically (Ca(2+)) cross-linked gels made from epimerised alginates expressed a higher degree of syneresis compared to the native samples. An increase in the modulus of elasticity was observed in calcium saturated (diffusion set) gels whereas calcium limited, internally set alginate gels showed no change in elasticity. An increase in the sol-gel transitional rate of gels made from epimerised alginates was also observed. These results suggest an increased possibility of creating new junction zones in the epimerised alginate gel due to the increased mobility in the alginate chain segments caused by the less extended alternating sequences.

Alginates↗

PubMed2002

Usefulness as guided bone regeneration membrane of the alginate membrane.

Alginate membrane is a new bioabsorbable, guided bone regeneration (GBR) membrane, which is placed directly on the surface of the bone defect. It is designed to drop a calcium chloride aqueous solution into the bone defect, which is filled with sodium alginate aqueous solution. Alginate membrane is an excellent agent for this procedure due to its close assimilation to the surface of the bone. In this study, we evaluated the short-term biocompatibility of alginate membrane in the bone defects of rat tibiae. GBR membrane availability was also examined. Consequently, we found that the healing process in bone defects covered with an alginate membrane was delayed in comparison with that of controls, however, the defect was restored to nearly original condition. In contrast, in the controls, bone defect repairs exhibited partitioning as a result of connective tissue involvement. Furthermore, we observed a relation between the sodium alginate concentration and the rate of absorption of the sodium alginate membrane. Absorption of a 1.5% sodium alginate membrane was slow. As a result, the compound was not absorbed completely and bone repairs resembled an hourglass. Moreover, the inflammatory response was absent surrounding the alginate membrane. The present findings suggested that the alginate membrane functions effectively as a GBR membrane. In addition, the alginate membrane derived from 3% calcium chloride and 1% sodium alginate was most suitable as a GBR membrane.

Absorption↗

PubMed2005

Direct evidence for Sphingomonas sp. A1 periplasmic proteins as macromolecule-binding proteins associated with the ABC transporter: molecular insights into alginate transport in the periplasm.

A Gram-negative bacterium, Sphingomonas sp. A1, has a macromolecule (alginate) import system consisting of a pit on the cell surface and an alginate-specific ATP-binding cassette importer in the inner membrane. Transport of alginate from the pit to the ABC importer is probably mediated by two periplasmic binding protein homologues (AlgQ1 and AlgQ2). Here we describe characteristics of binding of AlgQ1 and AlgQ2 to alginate and its oligosaccharides through surface plasmon resonance biosensor analysis, UV absorption difference spectroscopy, and X-ray crystallography. Both AlgQ1 and AlgQ2 were inducibly expressed in the periplasm of alginate-grown cells of strain A1. Biosensor analysis indicated that both proteins specifically bind alginate with a high degree of polymerization (>100) and that dissociation constants for alginate with an average molecular mass of 26 kDa are 2.3 x 10(-)(7) M for AlgQ1 and 1.5 x 10(-)(7) M for AlgQ2. An in vitro ATPase assay using the membrane complex, including the alginate ABC importer, suggested that both alginate-bound forms of AlgQ1 and AlgQ2 are closely associated with the importer. X-ray crystallography showed that AlgQ1 consisted of two domains separated by a deep cleft that binds alginate oligosaccharides through a conformational change in the two domains. These results directly show that alginate-binding proteins play an important role in the efficient transport of alginate macromolecules with different degrees of polymerization in the periplasm.

ATP-Binding Cassette Transporters↗

PubMed2000

Review article: alginate-raft formulations in the treatment of heartburn and acid reflux.

Alginate-based raft-forming formulations have been marketed word-wide for over 30 years under various brand names, including Gaviscon. They are used for the symptomatic treatment of heartburn and oesophagitis, and appear to act by a unique mechanism which differs from that of traditional antacids. In the presence of gastric acid, alginates precipitate, forming a gel. Alginate-based raft-forming formulations usually contain sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide which becomes entrapped within the gel precipitate, converting it into a foam which floats on the surface of the gastric contents, much like a raft on water. Both in vitro and in vivo studies have demonstrated that alginate-based rafts can entrap carbon dioxide, as well as antacid components contained in some formulations, thus providing a relatively pH-neutral barrier. Several studies have demonstrated that the alginate raft can preferentially move into the oesophagus in place, or ahead, of acidic gastric contents during episodes of gastro-oesophageal reflux; some studies further suggest that the raft can act as a physical barrier to reduce reflux episodes. Although some alginate-based formulations also contain antacid components which can provide significant acid neutralization capacity, the efficacy of these formulations to reduce heartburn symptoms does not appear to be totally dependent on the neutralization of bulk gastric contents. The strength of the alginate raft is dependant on several factors, including the amount of carbon dioxide generated and entrapped in the raft, the molecular properties of the alginate, and the presence of aluminium or calcium in the antacid components of the formulation. Raft formation occurs rapidly, often within a few seconds of dosing; hence alginate-containing antacids are comparable to traditional antacids for speed of onset of relief. Since the raft can be retained in the stomach for several hours, alginate-based raft-forming formulations can additionally provide longer-lasting relief than that of traditional antacids. Indeed, clinical studies have shown Gaviscon is superior to placebo, and equal to or significantly better than traditional antacids for relieving heartburn symptoms. Alginate-based, raft-forming formulations have been used to treat reflux symptoms in infants and children, and in the management of heartburn and reflux during pregnancy. While Gaviscon is effective when used alone, it is compatible with, and does not interfere with the activity of antisecretory agents such as cimetidine. Even with the introduction of new antisecretory and promotility agents, alginate-rafting formulations will continue to have a role in the treatment of heartburn and reflux symptoms. Their unique non-systemic mechanism of action provides rapid and long-duration relief of heartburn and acid reflux symptoms.

Adult↗

PubMed2001

Culture of chondrocytes in alginate surrounded by fibrin gel: characteristics of the cells over a period of eight weeks.

OBJECTIVE: To produce tissue engineered cartilage by human articular chondrocytes in vitro for further use in in vivo manipulations for the treatment of cartilage defects. METHODS: Human articular chondrocytes were cultured in 0.5%, 1.0%, and 2.0% of alginate for up to four weeks. The optimal concentration of an alginate matrix for cell replication and for aggrecan synthesis by chondrocytes was determined. DNA content in the different culture conditions was measured after two and four weeks. Aggrecan synthesis rates and accumulation in the surrounding extracellular matrix were assessed by [(35)S]sulphate incorporation after the same periods of culture. To follow the outgrowth of chondrocytes from the alginate beads, chondrocytes were cultured for four weeks in 0.5 or 1.0% alginate surrounded by 0.25 or 0.5% fibrin gel. DNA content of each culture was measured after different culture periods. Finally, human chondrocytes in 1.0% alginate beads were embedded in 0.5% fibrin gel for eight weeks. Immunohistochemical analysis for aggrecan, type I and II collagen was performed weekly. RESULTS: At two weeks the DNA content in each culture significantly increased in 0.5 and 1.0% alginate cultures in comparison with baseline values. This increase continued until week 4 at the three alginate concentrations. Aggrecan synthesis at two weeks was highest in 0.5 and 1.0% alginate cell cultures. At four weeks aggrecan synthesis rates decreased independently of the alginate concentrations. Aggrecan mainly accumulated in the interterritorial matrix. Proliferation of chondrocytes in alginate and outgrowth of these cells in the surrounding fibrin gel were evident throughout the culture period. The accumulation of aggrecan and type II collagen around the cells, in alginate as well as in fibrin gel, gradually increased over the culture period. Type I collagen appeared after six weeks in alginate and in the surrounding fibrin. CONCLUSION: Human chondrocytes proliferate in this culture system, show an outgrowth into the surrounding fibrin, and synthesise a cartilage-like matrix for up to eight weeks.

Aggrecans↗

PubMed1997

Development and characterization of an alginate-impregnated polyester vascular graft.

Alignate gels are known to be biocompatible, degradable, and nontoxic. In this study, sodium alginate was impregnated into a porous, knitted polyester graft (Microvel double velour graft) 6 mm in diameter. The alginate-impregnated graft was investigated in vitro and in vivo to evaluate its potential for use as a new vascular graft impervious to blood, while retaining high porosity for tissue ingrowth and biological healing. For in vitro investigation, the coating weight, water permeability, morphology, and mechanical properties of the alginate-impregnated grafts were compared to those of control or commercially available collagen-impregnated (Hemashield) grafts. The water permeability of the controls (1846 mL/min.cm2 at 120 mm Hg) was reduced > 99% by the alginate impregnation, rendering the graft impervious to blood. The coating weight of the alginate was 45 mg/g of graft, producing a much lower value than that of the collagen-impregnated model (310 mg/g). For in vivo investigation, the alginate-impregnated grafts were implanted in the aorta of mongrel dogs without preclotting for scheduled periods ranging from 4 h to 6 months. The control grafts after preclotting and the collagen-impregnated grafts without preclotting were also implanted for 3 and 6 months for comparison. Gross observation of the explanted grafts and histologic examination of the representative sections were conducted for three types of grafts using a light microscope after hematoxylin-eosin staining. No significant differences were observed between the histologic appearance of the alginate-impregnated grafts and that of the preclotted and collagen-impregnated grafts in terms of the degree of inflammation, foreign-body giant cell reaction, and intimal fibrosis. Endothelial-like cells were present on the midsections of all the grafts after 3 months of implantation. The resorption rate of alginate impregnated into the graft was also examined after staining the sections with periodic acid-Schiff reagent, Toluidine blue, and Alcian blue, which are specific for alginates. The staining alginate was partially visible between the graft fabrics up to 1 month after implantation, but was completely resorbed after 3 months. This preliminary study demonstrated that the use of an alginate as a biological sealant instead of proteins such as collagen, gelatin, and albumin may be a feasible approach to developing imprevious textile arterial prostheses, since the proteins have been reported to be generally unstable, hard to obtain in pure forms, not easy to crosslink and control resorption rate, and difficult to render compatible with standard storage and sterilization procedures.

Alginates↗

PubMed1999

Retention of hyaluronic acid in alginate beads: aspects for in vitro cartilage engineering.

Alginate has been used successfully for three-dimensional chondrocyte cultures and may be important for cartilage transplant formation. However, alginate is not a natural component of the cartilage matrix. The aim of this study was (a) to supplement alginate with the extracellular matrix component hyaluronic acid; and (b) to analyze the hyaluronic acid retention in different alginate gels. Hyaluronan is assumed to improve proteoglycan retention and may be important for in vitro matrix formation, tissue turgor, and biomechanical quality. Alginate and hyaluronan were mixed with chondrocytes and polymerized as were alginate, hyaluronan, and fibrinogen. [3H]hyaluronan was used to quantitate the leakage of hyaluronan from the gel beads. After 28 days in culture, 1.2% alginate beads supplemented with 0.26% hyaluronan contained only 9% of the initial amount of hyaluronan whereas 2.4% alginate beads still contained about 55% of the initial 0.22% hyaluronan. Release of hyaluronan from the beads was significantly lower if the beads additionally contained fibrin. Alginate beads supplemented with hyaluronan or fibrin showed increased chondrocyte proliferation compared to controls. Supplemented hyaluronan greatly diffuses out of alginate gels of lower densities. It must be assumed also that most of the hyaluronan newly synthesized by chondrocytes in these cells diffuses into the surrounding culture medium. The in vitro development of a sufficiently hygroscopic cartilage ground substance therefore may be very limited. Sufficient hyaluronic acid retention can be achieved in alginate gels with concentrations above 1.2% or by addition of fibrin.

Alginates↗

PubMed2002

Low-temperature electron microscopy for the study of polysaccharide ultrastructures in hydrogels. II. Effect of temperature on the structure of Ca2+-alginate beads.

Calcium alginate beads were thermally treated at temperatures ranging from 25 degrees C to 130 degrees C for periods of up to 30 minutes. Important modifications to the structure of the alginate beads were shown to be a function of the temperature and period of incubation at each temperature. Modifications to the alginate beads included reduction in size, mechanical resistance, and molecular weight cut-off with increasing temperature and incubation period. Thus, heating 700 microm calcium alginate beads for 20 min at 130 degrees C resulted in a 23% reduction in diameter, 70% increase in mechanical resistance, and 67% reduction in molecular weight cut-off. Incubation of calcium alginate beads containing 2 x 10(6) kDa blue dextran for 20 min at 130 degrees C resulted in no detectable loss of either dye or alginate. This indicates the shrinkage of the beads was due to re-arrangement of the alginate chains within the beads, coupled with loss of water. This hypothesis was verified by direct visual observation of calcium alginate beads before and after thermal treatment using cryo-scanning electron microscopy (cryo-SEM). Unlike other microscopy methods cryo-SEM offers the advantage of extremely rapid freezing which preserves the original structure of the alginate network. As a result cryo-SEM is a powerful tool for studies of hydrogel and capsule structure and formation. Differential scanning calorimetry (DSC) showed that the water entrapped in 2% alginate beads was present in a single state, irrespective of the thermal treatment. This result is attributed to the low alginate concentration used to form the beads.

Alginates↗

PubMed1997

Improved biocompatibility but limited graft survival after purification of alginate for microencapsulation of pancreatic islets.

Graft failure of alginate-polylysine microencapsulated islets is often interpreted as the consequence of a non-specific foreign body reaction against the microcapsules, initiated by impurities present in crude alginate. The aim of the present study was to investigate if purification of the alginate improves the biocompatibility of alginate-polylysine microcapsules. Alginate was purified by filtration, extraction and precipitation. Microcapsules prepared from crude or purified alginate were implanted in the peritoneal cavity of normoglycaemic AO-rats and retrieved at 1, 2, 3, 6, 9, and 12 months after implantation. With crude alginate, all capsules were overgrown within 1 month after implantation. With purified alginate, however, the portion of capsules overgrown was usually less than 10%, even at 12 months after implantation. All recipients of islet allografts in capsules prepared of purified alginate became normoglycaemic within 5 days after implantation, but hyperglycaemia reoccurred after 6 to 20 weeks. With intravenous and oral glucose tolerance test, all recipients had impaired glucose tolerance and insulin responses were virtually absent. After graft failure, capsules were retrieved (80-100%) by peritoneal lavage. Histologically, the percentage of overgrown capsules was usually less than 10% and maximally 31%. This small portion cannot explain the occurrence of graft failure. The immunoprotective properties of the capsules were confirmed by similar if not identical survival times of encapsulated islet allo- and isografts. Our results show that purification of the alginate improves the biocompatibility of alginate-polylysine microcapsules. Nevertheless, graft survival was still limited, most probably as a consequence of a lack of blood supply to the encapsulated islets.

Alginates↗

PubMed2006

Comparison of ready-made and self-setting alginate membranes used as a barrier membrane for guided bone regeneration.

In order to understand the requirements of guided bone regeneration (GBR) involving alginate base self-setting barrier membranes, GBR was performed in the case of bicortical bone defects formed at the tibiae of experimental animals employing self-setting and ready-made alginate membranes. Connective tissue ingress into the bone defects at the skin side of the tibia was observed when GBR was generated utilizing ready-made alginate membrane. In contrast, bone defects were reconstructed with bone tissue when GBR was generated with self-setting alginate membrane formed from aqueous 3% sodium alginate and 3% CaCl(2) solutions. The unreacted aqueous sodium alginate solution inherent to self-setting alginate membrane did not inhibit bone tissue regeneration. Rather, callus bone was formed using sodium alginate as the nucleus. However, when GBR was effected with self-setting alginate membrane formed from aqueous 10% CaCl(2) solution, membrane was too thick and thus regeneration of bone tissue in the bone cavity was prevented. Therefore, we concluded that self-setting alginate membrane is very useful as a barrier membrane for GBR upon appropriate adjustment of conditions with respect to preparation of alginate membrane.

Alginates↗

PubMed2005

Impact of residual contamination on the biofunctional properties of purified alginates used for cell encapsulation.

Alginate is frequently used for cell encapsulation, but its biocompatibility is neither optimal nor reproducible. Purifying the alginate is critical for achieving a suitable biocompatibility. However, published purification methods vary in efficiency and may induce changes in polymer biofunctionality. Applying X-ray photoelectron spectroscopy, we showed that commercial alginates, purified by in-house and industrial methods, contained elemental impurities that contributed 0.41-1.73% of their atomic composition. Residual contaminants were identified to be proteins (nitrogen/COOH), endotoxins (phosphorus), and fucoidans (sulphur). Studies using attenuated total reflectance Fourier transform infrared spectroscopy suggested that trace contamination did not alter the alginate molecular structure. Alginate hydrophilicity increased by 19-40% after purification, in correlation with a reduction in protein and polyphenol content. Solution viscosity of the alginate increased by 28-108% after purification, in correlation with a reduction in protein content. These results demonstrate that commercial alginates contain potentially immunogenic contaminants that are not completely eliminated by current purification methods. Moreover, these contaminants alter the functional properties of the alginate in a manner that may compromise biocompatibility: Hydrophilicity may affect protein adsorption and solution viscosity influences the morphology of alginate-based microcapsules. These findings highlight the need to improve and better control alginate purity to ensure a reproducible biofunctionality and optimal biocompatibility of alginate and microcapsules.

Alginates↗

PubMed2002

Biocompatibility of microcapsules for cell immobilization elaborated with different type of alginates.

The biocompatibility of alginate-PLL-alginate (APA) microcapsules has been evaluated with respect to impurity levels. The impurity content of three different alginates (a raw high M-alginate, a raw high G-alginate and a purified high G-alginate) has been determined and the in vivo antigenic response of APA beads made with each alginate assessed. Results show that purification of the alginate not only reduces the total amount of impurities (63% less in polyphenols, 91.45% less in endotoxins and 68.5% less in protein in relation to raw high M-alginate), but also avoids an antibody response when microcapsules of this material are implanted in mice. In contrast, raw alginates produced a detectable antibody response though the differences in their impurity content. Consequently, this work revealed that purity of the alginate rather than their chemical composition, is probably of greater importance in determining microcapsule biocompatibility.

Alginates↗

PubMedDate not supplied

Porous alginate--poly(ethylene glycol) entrapment system for the cultivation of mammalian cells.

A novel gel entrapment method has been developed where macropores are created within alginate beads to provide an environment for high-density growth of mammalian cells. The method takes advantage of an interaction between poly(ethylene glycol) (PEG) and alginate to provide a network of pores within the bead for growth while the surrounding alginate matrix retains the integrity of the bead and minimizes cell leakage. Hybridomas were grown to a density approaching 10(8) cells/mL of beads in this system, while conventional alginate restricted growth to a maximum of 2 x 10(7) cells/mL of beads. In addition, cell leakage was minimal even at high cell densities, which was not the case with the conventional alginate system. Study of the conventional system determined that cell growth was limited by the alginate matrix; increasing the alginate concentrations resulted in lower final cell densities. In contrast, the PEG-alginate system permits growth in pores so the alginate matrix serves only as a structural matrix for cells. The pore size can be varied as a function of PEG concentration (10-20 wt % PEG) to provide radially defined areas for cell growth and radial diffusion pathways for nutrients/products in the adjacent alginate matrix. Because the PEG-alginate entrapment process does not require additional chemical reactions or temperature changes, the system offers a simple alternative to attain high cell densities in an immobilized bead system. As an illustration of the concept, cells entrapped in this system were grown to high density in both batch and perfusion modes for the production of monoclonal antibodies. Using the suspension batch culture as the base case, the specific monoclonal antibody production rate increased 1.6-fold for the slower growing batch-immobilized culture and 3-fold for the immobilized perfusion culture.

Alginates↗

PubMed2003

Metal selectivity of Sargassum spp. and their alginates in relation to their alpha-L-guluronic acid content and conformation.

The discovery of a consistent and unusual enrichment in homopolymeric alpha-L-guluronic acid G-blocks in alginates extracted from a suite of Sargassum brown algae is described in this study. 1H NMR spectroscopy was used to characterize these alginates which display homopolymeric guluronic acid block (G-block) frequency values (F(GG)) between 0.37 and 0.81. The presence of these G-blocks results in an enhanced selectivity for cadmium or calcium relative to monovalent ions such as sodium and the proton as well as smaller divalent ions such as magnesium. Results of competitive exchange experiments for the Cd-Ca-alginate system yield selectivity coefficient, K*(Cd)Ca, values between 0.43 +/- 0.10 and 1.32 +/- 0.02 for a range in F(GG) of 0.23 to 0.81. In contrast to the Cd-Ca-alginate system, the Mg-Ca-alginate and Mg-Cd-alginate systems yielded maximum values of K*(Mg)Ca (18.0 +/- 1.4) and K*(Mg)Cd (16.0 +/- 0.9) for the alginates extracted from Sargassum fluitans (F(GG) = 0.81; Cuba) and Sargassum thunbergii (F(GG) = 0.75; Korea), respectively. Selectivity studies with mixed-metal pair alginate systems highlight the importance of the specific macromolecular conformation of the alginate polymer in determining metal binding behavior in multiple-metal systems. Furthermore, they demonstrate the importance of the conformation of the alginate as it occurs within the tissue of Sargassum in determining the metal binding behavior of this algal biosorbent. The unique composition of the alginates present in species of Sargassum may represent a distinct advantage over other brown algal species when considering their implementation for the strategic removal of toxic heavy metals from contaminated and industrial wastewaters.

Alginates↗

PubMed2002

Alginate in drug delivery systems.

Alginates are established among the most versatile biopolymers, used in a wide range of applications. The conventional use of alginate as an excipient in drug products generally depends on the thickening, gel-forming, and stabilizing properties. A need for prolonged and better control of drug administration has increased the demand for tailor-made polymers. Hydrocolloids like alginate can play a significant role in the design of a controlled-release product. At low pH hydration of alginic acid leads to the formation of a high-viscosity "acid gel." Alginate is also easily gelled in the presence of a divalent cation as the calcium ion. Dried sodium alginate beads reswell, creating a diffusion barrier decreasing the migration of small molecules (e.g., drugs). The ability of alginate to form two types of gel dependent on pH, i.e., an acid gel and an ionotropic gel, gives the polymer unique properties compared to neutral macromolecules. The molecule can be tailor-made for a number of applications. So far more than 200 different alginate grades and a number of alginate salts are manufactured. The potential use of the various qualities as pharmaceutical excipients has not been evaluated fully, but alginate is likely to make an important contribution in the development of polymeric delivery systems. This natural polymer is adopted by Ph.Eur. It can be obtained in an ultrapure form suitable for implants. This review discusses the present use and future possibilities of alginate as a tool in drug formulation.

Alginates↗