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Abstract

The utilisation of alginate polymers for wound healing is well explored; however, little attention is paid towards the optimisation of the manufacturing process, especially in regards to the final morphological and rheological properties that are imparted to the alginate matrix. This is important as it helps to establish a set of guidelines for the consistent fabrication of mechanically strong polymer wafers, which in the context of manufacturing and production contributes to the reduction in research and development time required. In this study, the order of application with respect to cross-linking and freeze-drying parameters have been investigated, which shown to result in distinct differences in terms of their overall morphology and mechanical strength. The application of freeze-drying before cross-linking results in the uniform distribution of cross-links throughout the alginate wafer, thereby producing a mechanically strong polymer wafer that retains the dehydrated matrices original thickness and architecture. Based on the observed data, freeze-drying prior to cross-linking facilitates the increased permeation and distribution of the cross-linker solution into the polymer matrix, thus resulting in the uniform distribution of ionic cross-links, which is necessary to produce a more mechanically superior polymer matrix.

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Alginates are natural polysaccharides available as seaweed products. They possess several properties due to their molecular structure made of bipolymeric α-L-Guluronic acid and β-D-Mannuronic acid polymers. Alginates have several properties such as film-forming ability, pH responsiveness, and gelling, hydrophilicity, biocompatibility, biodegradability, non-toxic, processability and ionic crosslinking. They’re commonly used in several industries, including food, pharmaceuticals, dental applications, welding rods and scaffolding. Due to their gelling and non-toxic properties, as well as their abundance in nature, the cosmetics and healthcare industries have shown a great deal of interest in biodegradable polymers in general and alginates particularly over the last few decades.
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Alginates are naturally occurring polysaccharides extracted from brown marine algae and bacteria. Being biocompatible, biodegradable, non-toxic and easy to gel, alginates can be processed into various forms, such as hydrogels, microspheres, fibers and sponges, and have been widely applied in biomedical field. The present review provides an overview of the properties and processing methods of alginates, as well as their applications in wound healing, tissue repair and drug delivery in recent years.
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Here, we report on studies on the influence of different crosslinking methods (ionic and chemical) on the physicochemical (swelling ability and degradation in simulated body fluids), structural (FT-IR spectra analysis) and morphological (SEM analysis) properties of SA/PVA hydrogels containing active substances of natural origin. First, an aqueous extract of Echinacea purpurea was prepared using a Soxhlet apparatus. Next, a series of modified SA/PVA-based hydrogels were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate (PEGDA, Mn = 700 g/mol) as a crosslinking agent and, additionally, the ionic reaction in the presence of a 5% w/v calcium chloride solution. The compositions of SA/PVA/E. purpurea-based hydrogels contained a polymer of natural origin—sodium alginate (SA, 1.5% solution)—and a synthetic polymer—poly(vinyl alcohol) (PVA, Mn = 72,000 g/mol, 10% solution)—in the ratio 2:1, and different amounts of the aqueous extract of E. purpurea—5, 10, 15 or 20% (v/v). Additionally, the release behavior of echinacoside from the polymeric matrix was evaluated in phosphate-buffered saline (PBS) at 37 °C. The results indicate that the type of the crosslinking method has a direct impact on the release profile. Consequently, it is possible to design a system that delivers an active substance in a way that depends on the application.
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Micron-sized alginate hydrogel beads are extensively employed as an encapsulation medium for biochemical and biomedical applications. Here we report on the microfluidic assisted fabrication of calcium alginate (Ca-alginate) beads by on-chip picoinjection of aqueous calcium chloride (CaCl2) in emulsified aqueous sodium alginate (Na-alginate) droplets or by picoinjection of Na-alginate solution in emulsified aqueous CaCl2 droplets. There is no added chelator to reduce the Ca activity in either of the two strategies. The two fabrication strategies are implemented using a flow-focusing and picoinjection modules in a single PDMS chip. Aqueous alginate solution was emulsified and infused with CaCl2 solution as the squeezed droplet pass the picoinjection channel; consequently, monodisperse, spherical, and structurally homogeneous Ca-alginate beads were obtained. Monodisperse alginate microgel populations with a mean diameter in the range of 8 to 28 µm and standard deviation less than 1 µm were successfully generated using microfluidic channels with various dimensions and controlling the flow parameters. Monodisperse but also non-spherical particles with diameters 6 to 15 µm were also fabricated when picoinjecting Na-alginate solution in emulsified aqueous CaCl2 droplets. The Ca-alginate microbeads fabricated with tailormade size in the range from sub-cellular and upwards were in both strategies realized without any use of chelators or change in pH conditions, which is considered a significant advantage for further exploitation as encapsulation process for improved enzymatic activity and cell viability.
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Alginates are widely used as gelling agents in textile print pastes, medical industries, impression material in dentistry, and anticoagulant material in toothpaste. In the present study, the content and spectroscopic characterization (1H NMR and FT-IR) of the sodium alginates were investigated in the eight brown seaweeds Sargassum muticum, Fucus vesiculosus f. volubilis, Carpodesmia tamariscifolia, Bifurcaria bifurcata, Laminaria ochroleuca, Cystoseira humilis, Saccorhiza polyschides, and Fucus guiryi harvested from the NW Atlantic coast of Morocco. The results proved that the most studied algae depicted alginate yields higher than 18% dry weight. The FT-IR analysis showed that the spectra of the extracted alginates exhibited significant similarities to the commercial alginate from Sigma-Aldrich. The 1H NMR spectroscopy indicated that the extracted alginates have a high content of β-D-mannuronic (M) than α-L-guluronic acid (G) with M/G ratio values ranging from 1.04 to 4.41. The homopolymeric fractions FMM are remarkably high compared to the FGG and heteropolymeric fractions (FGM = FMG) especially for F. guiryi, C humilis, C. tamariscifolia, L. ochroleuca, and S. polyschides. Nevertheless, the heteropolymeric fractions (FGM/FMG) are quite abundant in the alginates of S. muticum, F. vesiculosus f. volubilis, and B. bifurcata accounting for more than 52% of the polymer diads. Based on these results, the investigated algal species (except Fucus guiryi and Bifurcaria bifurcata) could be regarded as potential sources of alginates for industrial uses.
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Hydrogels are a three-dimensional and crosslinked network of hydrophilic polymers. They can absorb a large amount of water or biological fluids, which leads to their swelling while maintaining their 3D structure without dissolving (Zhu and Marchant, Expert Rev Med Devices 8:607–626, 2011). Among the numerous polymers which have been utilized for the preparation of the hydrogels, polysaccharides have gained more attention in the area of pharmaceutics; Sodium alginate is a non-toxic, biocompatible, and biodegradable polysaccharide with several unique physicochemical properties for which has used as delivery vehicles for drugs (Kumar Giri et al., Curr Drug Deliv 9:539–555, 2012). Owing to their high-water content and resembling the natural soft tissue, hydrogels were studied a lot as a scaffold. The formation of hydrogels can occur by interactions of the anionic alginates with multivalent inorganic cations through a typical ionotropic gelation method. However, those applications require the control of some properties such as mechanical stiffness, swelling, degradation, cell attachment, and binding or release of bioactive molecules by using the chemical or physical modifications of the alginate hydrogel. In the current review, an overview of alginate hydrogels and their properties will be presented as well as the methods of producing alginate hydrogels. In the next section of the present review paper, the application of the alginate hydrogels will be defined as drug delivery vehicles for chemotherapeutic agents. The recent advances in the application of the alginate-based hydrogels will be describe later as a wound dressing and bioink in 3D bioprinting.
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The interest toward alginate and nanoemulsion-based hydrogels is driven by the wide potential of application. These systems have been noticed in several areas, ranging from pharmaceutical, medical, coating, and food industries. In this investigation, hydrogels prepared through in situ calcium ion release, starting from lemongrass essential oil nanodispersions stabilized in alginate aqueous suspensions in the presence of the nonionic surfactant Tween 80, were evaluated. The hydrogels prepared at different concentrations of oil, alginate, and calcium were characterized through rheological tests. Flow curves demonstrate that the hydrogels share shear thinning behavior. Oscillatory tests showed that the strength of the hydrogel network increases with the crosslinker increase, and decreases at low polymer concentrations. The hydrogels were thixotropic materials with a slow time of structural restoration after breakage. Finally, by analyzing the creep recovery data, the hydrogel responses were all fitted to the Burger model. Overall, it was demonstrated that the presence of essential oil in the proposed hydrogels does not affect the mechanical characteristics of the materials, which are mainly influenced by the concentration of polymer and calcium as a crosslinker.
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More and more water-absorbing wound dressings have been studied since moist wound-healing treatment can effectively promote the healing of wounds. In this work, we introduce a novel method to produce improved wound dressings with high-water-absorbance. A high-water-absorbing calcium alginate (Ca-Alg) fibrous scaffold was fabricated simply by microfluidic spinning and centrifugal reprocessing. The structure and physical properties of the scaffold were characterized, and its water-absorbing, cytotoxicity properties and other applicability to wound dressings were comprehensively evaluated. Our results indicate that this material possesses high water-absorbing properties, is biocompatible, and has a 3D structure that mimics the extracellular matrix, while Ca-Alg fibers loaded with silver nanoparticles (AgNPs) exhibit broad-spectrum antibacterial activities; these properties meet the requirements for promoting the healing of chronic wounds and are widely applicable to wound dressings.
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Alginate is a biopolymer used in a variety of biomedical applications due to its favourable properties, such as biocompatibility and non-toxicity. It has been particularly attractive in wound healing applications to date. It can be tailored to materials with properties suitable for wound healing. Alginate has been used to prepare different forms of materials for wound dressings, such as hydrogels, films, wafers, foams, nanofibres, and in topical formulations. The wound dressings prepared from alginate are able to absorb excess wound fluid, maintain a physiologically moist environment, and minimize bacterial infections at the wound site. The therapeutic efficacy of these wound dressings is influenced by the ratio of other polymers used in combination with alginate, the nature of cross linkers used, the time of crosslinking, nature of excipients used, the incorporation of nanoparticles, and antibacterial agents. This review provides a comprehensive overview of the different forms of wound dressings containing alginate, in vitro, and in vivo results.
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Chapter
The biopolymeric hydrogels are being employed as the promising carriers for delivery of numerous kinds of drug candidates. Hydrogel systems are capable of absorbing higher volume of aqueous fluid while keeping intactness of the structural features. These also provide an easy implementation of the targeted and controlled releasing of drugs to the specific organs. Their use can minimize the unfavorable side effects of conventional drug delivery. Alginate is an abundant natural polysaccharide that possesses various freely existing hydroxyl and carboxyl functional groups along with its structural backbone and thus can be modified chemically. Alginate-based hydrogels have been designed by using different strategies which are either based on various kinds of physical and/or chemical cross-linking methodologies. Recent years, the drug delivery research and development have witnessed a tremendous growth for the prospective use of various alginate-based hydrogels. Due to increasing interest and great potential of these alginate-based hydrogels, this chapter is intended to present a comprehensive overview of the existing state-of-the-art technology in producing various alginate-based hydrogels and their evaluations for the use in drug delivery.
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This review focuses on recently developed alginate injectable hydrogels and alginate composites for applications in bone tissue regeneration, and it evaluates the alternatives to overcome the problems that avoid their utilization in the field. Section 2 covers the properties of alginates that have made them useful for medical applications, in particular their ionic gelling ability for preparing injectable compositions used as delivery drugs systems. The advantages and shortcomings of these preparations are revised together with the chemical modifications assayed. Section 3 describes how it has been taken advantage of alginates into the new field of biofabrication and the developments in bone engineering. The state of the art of this field is reviewed. Finally in section 4, new developments and approaches that in opinion of the authors can lead to a breakthrough in bone tissue engineering using alginates are introduced
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Calcium alginate (CA) wafer dressings were prepared by lyophilization of hydrogels to deliver ciprofloxacin (CIP) directly to the wound site of infected diabetic foot ulcers (DFUs). The dressings were physically characterized by scanning electron microscopy (SEM), texture analysis (for mechanical and in vitro adhesion properties), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Further, functional properties essential for wound healing, i.e., porosity, in vitro swelling index, water absorption (Aw), equilibrium water content (EWC), water vapor transmission rate (WVTR), evaporative water loss (EWL), moisture content, in vitro drug release and kinetics, antimicrobial activity, and cell viability (MTT assay) were investigated. The wafers were soft, of uniform texture and thickness, and pliable in nature. Wafers showed ideal wound dressing characteristics in terms of fluid handling properties due to high porosity (SEM). XRD confirmed crystalline nature of the dressings and FTIR showed hydrogen bond formation between CA and CIP. The dressings showed initial fast release followed by sustained drug release which can inhibit and prevent re-infection caused by both Gram-positive and Gram-negative bacteria. The dressings also showed biocompatibility (> 85% cell viability over 72 h) with human adult keratinocytes. Therefore, it will be a potential medicated dressing for patients with DFUs infected with drug-resistant bacteria.
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Abstract Calcium alginate nanoparticles as excellent carriers in drug delivery systems were synthesized by controlled gellification method and characterized with Fourier Transform Infrared spectroscopy (FTIR). To compare mean particle size and distribution of calcium alginate nanoparticles with homopolymannuronate ones, later nanoparticles were prepared through the same conditions. Sodium homopolymannuronate is one of the ingredients of alginate polymer which was synthesized and purified by partial acid hydrolysis of sodium alginate and characterized with FTIR spectroscopy. Results showed significant improvement of size and distribution of calciumalginate nanoparticleswith decrease of sodium alginate and increase of calcium cation concentrations, respectively. In addition, lower mean particle size and better distribution of calciumhomopolymannuronate nanoparticleswas observed in comparisonwith calciumalginate ones. This resultmay refer to the ionic interaction of calciumcrosslinker ionswith regular homopolymeric chains of homopolymannuronate compared to no regular chains of alginate polymer.
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Objective: The purpose of this study was to compare the total oxidant and antioxidant effect of different oral iron preparations in children with iron-deficiency anemia (IDA). Methods: A total of 65 children with IDA were randomized to receive 5 mg Fe/kg/d iron (II) sulfate (Fe(2+) group, n=33) or iron (III)-hydroxide polymaltose complex (Fe(3+) group, n=32); healthy controls (n=28) were also included in the study. Serum total thiol (-SH), total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and hematological profile were evaluated at the baseline and on day 8 and day 30 of the therapy. Results: Serum TOS and OSI levels were significantly higher and total -SH and total antioxidant capacity levels were significantly lower in the study groups at the beginning of therapy than in the controls (P>0.001). In multivariate analysis, after controlling for multiple confounding factors, on days 8 and 30, serum TOS and OSI levels were not different in the Fe(3+) group, whereas they were significantly reduced in the Fe(2+) group (P≤0.033). Conclusions: Serum total oxidant status was significantly increased in children with IDA, and Fe(2+) was highly effective in correcting elevated oxidative status.
Article
Calcium alginate dressings have beneficial effects on wound healing by providing a moist wound environment. However, cytotoxicity and the nonbiodegradable nature of calcium alginate dressings induce unresolved chronic foreign-body reaction. In this study, a novel freeze-dried alginate gel dressing (AGA-100) low in calcium ions was evaluated for cytotoxicity to L929 cells in vitro and in full-thickness pig wounds in vivo. Cytotoxicity testing on L929 cells showed the cytocompatibility of AGA-100 extracts, while extracts from Kaltostat, a well-established alginate dressing, induced cytopathic effects. In an in vivo study using pigskin, AGA-100, Kaltostat, and gauze were applied on 1-in-diameter circular full-thickness wounds on the back of pigs and the time course of wound closure was evaluated. Kaltostat and gauze dressings were used as controls. For histologic evaluation, wound tissue was harvested on day 18. AGA-100-treated wounds showed rapid wound closure compared to control wounds on day 15. Foreign-body reaction was marked in Kaltostat- and gauze-treated wounds, and differed significantly from AGA-100-treated wounds. Based on these data, AGA-100 could reduce the cytotoxicity to fibroblasts and foreign-body reaction that have been observed with currently available calcium alginate dressings; it was also found to be useful as an alginate dressing. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 317–322, 1998.
Article
Alginate is a biomaterial that has found numerous applications in biomedical science and engineering due to its favorable properties, including biocompatibility and ease of gelation. Alginate hydrogels have been particularly attractive in wound healing, drug delivery, and tissue engineering applications to date, as these gels retain structural similarity to the extracellular matrices in tissues and can be manipulated to play several critical roles. This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.
Article
The properties of alginate films modified using two cross-linker ions (Ca(2+) and Ba(2+)), comparing two separate cross-linking techniques (the traditional immersion (IM) method and a new strategy in a pressure-assisted diffusion (PD) method), are evaluated. This was achieved through measuring metal ion content, water uptake and film stability in an ionic solution ([Ca(2+)] = 2 mM). Characterization of the internal structure and mechanical properties of hydrated films were established by cryogenic scanning electron microscopy and tensile testing, respectively. It was found that gels formed by the PD technique possessed greater stability and did not exhibit any delamination after 21 day immersion as compared to gels formed by the IM technique. The Ba(2+) cross-linked gels possessed significantly higher cross-linking density as reflected in lower water content, a more dense internal structure and higher Young's modulus compared to Ca(2+) cross-linked gels. For the Ca(2+) cross-linked gels, a large improvement in the mechanical properties was observed in gels produced by the PD technique and this was attributed to thicker pore walls observed within the hydrogel structure. In contrast, for the Ba(2+) cross-linked gels, the PD technique resulted in gels that had lower tensile strength and strain energy density and this was attributed to phase separation and larger macropores in this gel.
Article
FTIR spectroscopy was used in order to obtain information about metal-carboxylate interactions in metal-alginate complexes of alginic acid and sodium alginate from the brown algae Laminaria digitata after crosslinking with Ca(2+), Cu(2+), Cd(2+), Zn(2+), Ni(2+) and Pb(2+). From the frequencies of the characteristic peaks for asymmetric COO stretching vibration (nu(asym)(COO(-)) and symmetric COO stretching vibration (nu(sym)(COO(-))) a 'pseudo bridged' unidentate coordination with intermolecular hydrogen bonds is proposed for the metal-carboxylate complexes in polyguluronic regions while for the polymannuronic regions the bidentate bridging coordination was proposed. The PIB factor introduced previously as a relationship between metal sorption and frequencies of the asymmetric vibrations was found not to correlate with sorption capacity or any other physical property of the metal-alginate complexes studied.
Article
This work investigates an application of the alginate encapsulation technology to the differentiation of embryonic stem (ES) cells into insulin-producing cells. It shows that the ES cells can efficiently be encapsulated within the alginate beads, retaining a high level of cell viability. The alginate encapsulation achieves approximately 10-fold increase in the cell density in the culture, in comparison to the two-dimensional conditions, opening a potential benefit of the technology in large-scale cell culture applications. Manipulations of encapsulation conditions, particularly of the initial alginate concentration, allow the control over both the diffusion of molecules into the alginate matrix (e.g. differentiation factors) as well as control over the matrix porosity/flexibility to permit the proliferation and growth of encapsulated ES aggregates within the bead. Post-differentiation analysis confirms the presence of insulin-positive cells, as judged from immunostaining, insulin ELISA and RT-PCR analysis. The functionality of the encapsulated and differentiated cells was confirmed by their insulin production capability, whereby on glucose challenge the insulin production by the cells differentiated within alginate beads was found to be statistically significantly higher than for the cells from conventional two-dimensional differentiation system.
Article
Alginate is a copolymer of beta-D-mannuronic acid and alpha-L-guluronic acid (GulA), linked together by 1-4 linkages. The polymer is a well-established industrial product obtained commercially by harvesting brown seaweeds. Some bacteria, mostly derived from the genus Pseudomonas and belonging to the RNA superfamily I, are also capable of producing copious amounts of this polymer as an exopolysaccharide. The molecular genetics, regulation and biochemistry of alginate biosynthesis have been particularly well characterized in the opportunistic human pathogen Pseudomonas aeruginosa, although the biochemistry of the polymerization process is still poorly understood. In the last 3 years major aspects of the molecular genetics of alginate biosynthesis in Azotobacter vinelandii have also been reported. In both organisms the immediate precursor of polymerization is GDP-mannuronic acid, and the sugar residues in this compound are polymerized into mannuronan. This uniform polymer is then further modified by acetylation at positions O-2 and/or O-3 and by epimerization of some of the residues, leading to a variable content of acetyl groups and GulA residues. In contrast, seaweed alginates are not acetylated. The nature of the epimerization steps are more complex in A. vinelandii than in P. aeruginosa, while other aspects of the biochemistry and genetics of alginate biosynthesis appear to be similar. The GulA residue content and distribution strongly affect the physicochemical properties of alginates, and the epimerization process is therefore of great interest from an applied point of view. This article presents a survey of our current knowledge of the molecular genetics and biochemistry of bacterial alginate biosynthesis, as well as of the biotechnological potential of such polymers.
Article
Alginate gels have been used in both drug delivery and cell encapsulation applications in the bead form usually produced by dripping alginate solution into a CaCl2 bath. The major disadvantages to these systems are that the gelation rate is hard to control; the resulting structure is not uniform; and mechanically strong and complex-shaped 3-D structures are difficult to achieve. In this work controlled gelation rate was achieved with CaCO3-GDL and CaSO4-CaCO3-GDL systems, and homogeneous alginate gels were formulated as scaffolds with defined dimensions for tissue engineering applications. Gelation rate increased with increasing total calcium content, increasing proportion of CaSO4, increasing temperature and decreasing alginate concentration. Mechanical properties of the alginate gels were controlled by the compositional variables. Slower gelation systems generate more uniform and mechanically stronger gels than faster gelation systems. The compressive modulus and strength increased with alginate concentration, total calcium content, molecular weight and guluronic acid (G) content of the alginate. MC3T3-E1 osteoblastic cells were uniformly incorporated in the alginate gels and cultured in vitro. These results demonstrated how alginate gel and gel/cell systems could be formulated with controlled structure, gelation rate, and mechanical properties for tissue engineering and other biomedical applications.
Article
The protein pharmaceutical market is rapidly growing, since it is gaining support from the recombinant DNA technology. To deliver these drugs via the oral route, the most preferred route, is the toughest challenge. In the design of oral delivery of peptide or protein drugs, pH sensitive hydrogels like alginate and chitosan have attracted increasing attention, since most of the synthetic polymers are immunogenic and the incorporation of proteins in to these polymers require harsh environment which may denature and inactivate the desired protein. Alginate is a water-soluble linear polysaccharide composed of alternating blocks of 1-4 linked alpha-L-guluronic and beta-D-mannuronic acid residues where as chitosan is a co polymer of D-glucosamine and N-acetyl glucosamine. The incorporation of protein into these two matrices can be done under relatively mild environment and hence the chances of protein denaturation are minimal. The limitations of these polymers, like drug leaching during preparation can be overcome by different techniques which increase their encapsulation efficiency. Alginate, being an anionic polymer with carboxyl end groups, is a good mucoadhesive agent. The pore size of alginate gel microbeads has been shown to be between 5 and 200 nm and coated beads and microspheres are found to be better oral delivery vehicles. Cross-linked alginate has more capacity to retain the entrapped drugs and mixing of alginate with other polymers such as neutral gums, pectin, chitosan, and eudragit have been found to solve the problem of drug leaching. Chitosan has only limited ability for controlling the release of encapsulated compound due to its hydrophilic nature and easy solubility in acidic medium. By simple covalent modifications of the polymer, its physicochemical properties can be changed and can be made suitable for the peroral drug delivery purpose. Ionic interactions between positively charged amino groups in chitosan and the negatively charged mucus gel layer make it mucoadhesive. The favourable properties like biocompatibility, biodegradability, pH sensitiveness, mucoadhesiveness, etc. has enabled these polymers to become the choice of the pharmacologists as oral delivery matrices for proteins.
Article
We describe the manufacture of highly stable and elastic alginate membranes with good cell adhesivity and adjustable permeability. Clinical grade, ultra-high viscosity alginate is gelled by diffusion of Ba2+ followed by use of the "crystal gun" [Zimmermann H. et al., Fabrication of homogeneously cross-linked, functional alginate microcapsules validated by NMR-, CLSM- and AFM-imaging. Biomaterials 2003;24:2083-96]. Burst pressure of well-hydrated membranes is between 34 and 325kPa depending on manufacture and storage details. Water flows induced by sorbitol and raffinose (probably diffusional) are lower than those caused by PEG 6000, which may be related to a Hagen-Poiseuille flow. Hydraulic conductivity, L(p), from PEG-induced flows ranges between 2.4x10(-12) and 6.5x10(-12) m Pa(-1)s(-1). Hydraulic conductivity measured with hydrostatic pressure up to 6 kPa is 2-3 orders of magnitude higher and decreases with increasing pressure to about 3x10(-10) m Pa(-1)s(-1) at 4kPa. Mechanical introduction of 200 microm-diameter pores increases hydraulic conductivity dramatically without loss of mechanical stability or flexibility. NMR imaging with Cu2+ as contrast agent shows a layered structure in membranes cross-linked for 2h. Phase contrast and atomic force microscopy in liquid environment reveals surface protrusions and cavities correlating with steps of the production process. Murine L929 cells adhere strongly to the rough surface of crystal-bombarded membranes. NaCl-mediated membrane swelling can be prevented by partial replacement of salt with sorbitol allowing cell culture on the membranes.
Article
Although the essentiality of zinc for plants and animals has been known for many decades, the essentiality of zinc for humans was recognized only 40 years ago in the Middle East. The zinc-deficient patients had severe immune dysfunctions, inasmuch as they died of intercurrent infections by the time they were 25 years of age. In our studies in an experimental human model of zinc deficiency, we documented decreased serum testosterone level, oligospermia, severe immune dysfunctions mainly affecting T helper cells, hyperammonemia, neurosensory disorders, and decreased lean body mass. It appears that zinc deficiency is prevalent in the developing world and as many as two billion subjects may be growth retarded due to zinc deficiency. Besides growth retardation and immune dysfunctions, cognitive impairment due to zinc deficiency also has been reported recently. Our studies in the cell culture models showed that the activation of many zinc-dependent enzymes and transcription factors were adversely affected due to zinc deficiency. In HUT-78 (T helper 0 [Th(0)] cell line), we showed that a decrease in gene expression of interleukin-2 (IL-2) and IL-2 receptor alpha(IL-2Ralpha) were due to decreased activation of nuclear factor-kappaB (NF-kappaB) in zinc deficient cells. Decreased NF-kappaB activation in HUT-78 due to zinc deficiency was due to decreased binding of NF-kappaB to DNA, decreased level of NF-kappaB p105 (the precursor of NF-kappaB p50) mRNA, decreased kappaB inhibitory protein (IkappaB) phosphorylation, and decreased Ikappa kappa. These effects of zinc were cell specific. Zinc also is an antioxidant and has anti-inflammatory actions. The therapeutic roles of zinc in acute infantile diarrhea, acrodermatitis enteropathica, prevention of blindness in patients with age-related macular degeneration, and treatment of common cold with zinc have been reported. In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8. We have reported recently that in both young adults and elderly subjects, zinc supplementation decreased oxidative stress markers and generation of inflammatory cytokines.
Article
Current membrane-based bioartificial organs consist of three basic components: (1) a synthetic membrane, (2) cells that secrete the product of interest, and (3) an encapsulated matrix material. Alginate and agarose have been widely used to encapsulate cells for artificial organ applications. It is important to understand the degree of transport resistance imparted by these matrices in cell encapsulation to determine if adequate nutrient and product fluxes can be obtained. For artificial organs in xenogeneic applications, it may also be important to determine the extent of immunoprotection offered by the matrix material. In this study, diffusion coefficients were measured for relevant solutes [ranging in size from oxygen to immunoglobulin G (IgG)] into and out of agarose and alginate gels. Alginate gels were produced by an extrusion/ionic crosslinking process using calcium while agarose gels were thermally gelled. The effect of varying crosslinking condition, polymer concentration, and direction of diffusion on transport was investigated. In general, 2-4% agarose gels offered little transport resistance for solutes up to 150 kD, while 1.5-3% alginate gels offered significant transport resistance for solutes in the molecular weight range 44-155 kD-lowering their diffusion rates from 10- to 100-fold as compared to their diffusion in water. Doubling the alginate concentration had a more significant effect on hindering diffusion of larger molecular weight species than did doubling the agarose concentration. Average pore diameters of approximately 170 and 147 A for 1.5 and 3% alginate gels, respectively, and 480 and 360 A for 2 and 4% agarose gels, respectively, were estimated using a semiempirical correlation based on diffusional transport of different-size solutes. The method developed for measuring diffusion in these gels is highly reproducible and useful for gels crosslinked in the cylindrical geometry, relevant for studying transport through matrices used in cell immobilization in the hollow fiber configuration. (c) 1996 John Wiley & Sons, Inc.
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