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PubMed2005

Liquid phase coating to produce controlled-release alginate microspheres.

This study explored a liquid phase coating technique to produce polymethyl methacrylate (PMMA)-coated alginate microspheres. Alginate microspheres with a mean diameter of 85.6 microm were prepared using an emulsification method. The alginate microspheres, as cores, were then coated with different types of PMMA by a liquid phase coating technique. The release characteristics of these coated microspheres in simulated gastric (SGF) and intestinal (SIF) fluids and the influence of drug load on encapsulation efficiency were studied. The release of paracetamol, as a model hydrophilic drug, from the coated microspheres in SGF and SIF was greatly retarded. Release rates of Eudragit RS100-coated microspheres in SGF and SIF were similar as the rate-controlling polymer coat was insoluble in both media. Drug release from Eudragit S100-coated microspheres was more sustained in SGF than in SIF, due to the greater solubility of the coating polymer in media with pH greater than 7.0. The drug release rate was affected by the core:coat ratio. Drug release from the coated microspheres was best described by the Higuchi's square root model. The liquid phase coating technique developed offers an efficient method of coating small microspheres with markedly reduced drug loss and possible controlled drug release.

Acetaminophen↗
PubMedDate not supplied

Stability of chitosan and poly-L-lysine membranes coating DNA-alginate beads when exposed to hydrolytic enzymes.

Soluble chitosan and poly-L-lysine are readily hydrolysed using lysozyme or chitosanase for chitosan, and trypsin, chymotrypsin or proteinase K for poly-L-lysine. For similar amounts of enzyme, chitosanase hydrolysed 57% of the chitosan, compared to 35% for lysozyme. In the case of poly-L-lysine, chymotrypsin and trypsin exhibited similar activities, hydrolysing approximately 41% of the polymer compared to proteinase K at only 16%. In contrast, chitosan and poly-L-lysine membranes, coating alginate beads, were almost totally inert to the respective hydrolytic enzymes. Less than 2% of the membrane weight was hydrolysed. It appears that either membrane material would be stable for in vivo application, and in particular in the protection of DNA during gastrointestinal transit. At chitosanase concentrations of 1.4 mg/ml and in the presence of sodium ions, 20% of the total double-stranded DNA was released from chitosan coated beads. An exchange of calcium for sodium within the bead liquefied the alginate core releasing DNA. The presence of calcium stabilized the alginate bead, retaining all the DNA. Highly pure DNA was recovered from beads through mechanical membrane disruption, core liquefaction in citrate and use of DNA spin-columns to separate DNA/alginate mixtures in a citrate buffer. DNA recovery efficiencies as high as 94% were achieved when the initial alginate/DNA weight ratio was 1000.

Acetylglucosamine↗
PubMed2002

Effects of alginate hydrogels and TGF-beta 1 on human dental pulp repair in vitro.

The objective of this study was to investigate the use of alginate hydrogels to present either exogenous or endogenous transforming growth factor (TGF)-beta 1 to the dentin-pulp complex to signal reparative processes. Hydrogels were prepared, applied to cultured human tooth slices and the effects on tertiary dentinogenesis examined histologically. Both TGF-beta 1-containing and acid-treated alginate hydrogels, but not untreated hydrogels, upregulated dentin matrix secretion and induced odontoblast-like cell differentiation with subsequent secretion of regular tubular dentin matrix on cut pulpal surfaces. It is concluded that TGF-beta 1 can signal both induction of odontoblast-like cell differentiation and upregulation of their matrix secretion in the human dentin-pulp complex. Alginate hydrogels provide an appropriate matrix in which dental regeneration can take place and may also be useful for delivery of growth factors, including TGF-beta s, to enhance the natural regenerative capacity of the dental pulp.

Acids↗
PubMed2006

Characterization of calcium alginate beads containing structurally similar drugs.

The aim of this study was to investigate the characteristics of alginate beads prepared by ionotropic gelation in which structurally similar drugs were incorporated. For this purpose theophylline and theobromine were selected as model drugs. The influence of incorporated drugs on bead characteristics such as size, shape, and morphology, as well as encapsulation efficiency, was examined. It was found that theobromine as well as theophylline content in beads significantly decreased with increasing hardening time due to drug diffusion into the hardening media. In theobromine beads the drug content was extremely improved by dropping the alginate and drug solution into an acidic calcium chloride solution, while theophylline content was to some extent improved by the hardening of beads in a calcium chloride solution saturated with the drug. The most evident difference between theophylline and theobromine beads was in their shape and morphology. Theobromine beads were round, while theophylline ones had an irregular shape with an extremely wrinkled surface. The distinction in shape was highly dependent on drug content. Additionally, it was demonstrated that beads' shape was dependent on preparation conditions as well. On the basis of x-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analyses and scanning electron microscope (SEM) photographs it was found that the most of the drug in bead was present in an amorphous state. Therefore, it is suggested that some drug-alginate interactions could be present in beads and might be responsible for the different shape of theophylline and theobromine beads. Thus it can be concluded that the preparation of beads by ionotropic gelation cannot be generalized even though structurally similar drugs are incorporated.

Alginates↗
PubMed2006

Effect of chitosan-coated alginate microspheres on the permeability of Caco-2 cell monolayers.

Alginate microspheres were prepared by emulsification/internal gelation and coated with chitosan. The ability of chitosan-coated alginate microspheres to increase the paracellular transport across Caco-2 cell monolayers was evaluated in comparison to uncoated microspheres and chitosan solutions. Transport studies were performed by using a permeability marker, Lucifer Yellow (LY), and by measuring the transepithelial electric resistance (TEER) variations. Furthermore, the occurrence of cytotoxic effects was assessed by evaluating neutral red uptake in viable cells and lactate dehydrogenase (LDH) release from damaged cells. A 3-fold increase on LY permeability was obtained for coated microspheres when compared to chitosan solutions. TEER variations were in agreement with permeability results. Chitosan solutions exhibited a dose-dependent toxicity, but coated microspheres did not decrease the viability of cells. Chitosan-coated alginate microspheres have potential to be used as carriers of poorly absorbable hydrophilic drugs to the intestinal epithelia and possibly increase their oral bioavailability.

Alginates↗
PubMed1979

Sparing of bone marrow stem cells by long-term administration of Na-alginate to 226Ra contaminated mice.

226Ra toxicity studies form the experimental basis for the estimation of radiation risk from internal emitters in man. We investigated whether treatment with Na-alginate is able to protect haemopoietic bone marrow cells against alpha-irradiation from 226Ra contamination. Doses from 4 to 14 micronCi/kg were injected intraperitoneally in mice 12 days before the start of the treatment. Damage to marrow stem cells was assessed by the exogene clonal spleen technique. Collection of marrow cells by two methods was compared. In the lower dose groups no influence on stem cell survival is noticed. but from 9.0 micronCi/kg a decrease in the number of surviving stem cells is observable in non treated animals. while in animals treated with Na-alginate fewer stem cells are damaged. These preliminary data agree with the hypothesis that Na-alginate stimulates removal of 226Ra mainly from the endosteal bone surfaces, reducing the local 226 Ra dose which accounts for damage to marrow stem cells within the range of alpha-rays at the endosteal surfaces.

Alginates↗
PubMedDate not supplied

A crosslinked calcium-alginate-pectinate-cellulose acetophthalate gelisphere system for linear drug release.

This study proposes a novel binary crosslinked ternary multiple-unit system, collectively referred to as calcium-alginate-pectinate-cellulose acetophthalate gelispheres (CAPCA), for the purpose of obtaining linear, controlled drug release. This polymeric system, composed of sodium alginate, pectin, and cellulose acetophthalate, was developed through a binary crosslinking reaction in a composite aqueous system consisting of calcium and acetate ions. The crosslinking reaction was optimized in terms of maximizing drug release suppression and could be obtained by exposing the gelispheres for 24 hours to a combined aqueous solution of 15% w/v acetic acid and 2% w/v calcium chloride. The highly acidic nature of this solution (pH 1.9) was desirable for enhancing the drug entrapment efficiency of the gelispheres. Synchronization of matrix swelling and erosion appeared to be responsible for the attainment of zero-order drug release. However, such perfect synchronization was only achievable through application of the ternary polymeric combination presented in this work. The main advantages of the ternary system shown in this study over the previously presented binary calcium-alginate-pectinate system (CAP) proposed by Pillay and Fassihi (1999a, 1999b), was provision of extended drug release over 18 hours, minimization of late-phase drug release tapering, and provision of superior linearity in drug release profiles. Kinetic modeling of dissolution data using various power law equations highlighted the significance of matrix relaxation and erosion in modulation of drug release rate. In all cases of model fitting excellent correlation (r(2) > 0.98) was obtained between observed and predicted data. Textural profiling of crosslinked gelispheres reflected a significantly lower reduction in matrix resilience as the concentration of cellulose acetophthalate was increased in the gelisphere formulation. This may be attributed to the concentration-dependent matrix plastic-transforming property of cellulose acetophthalate.

Alginates↗
PubMed2001

Chitosan-alginate microparticles as a protein carrier.

The oral administration of peptidic drugs requires their protection from degradation in the gastric environment and the improvement of their absorption in the intestinal tract. For these requirements, a microsystem based on cross-linked alginate as the carrier of bovine serum albumin (BSA), used as a model protein, was proposed. A spray-drying technique was applied to BSA/sodium alginate solutions to obtain spherical particles having a mean diameter less than 10 microm. The microparticles were hardened using first a solution of calcium chloride and then a solution of chitosan (CS) to obtain stable microsystems. The cross-linking process was carried out at different CS concentrations and pH values of the cross-linking medium. The CS concentration affected the BSA loading in the microparticles prepared at a pH value less than the protein isoelectric point (pI). Moreover, the BSA loading at a pH value less than the pI was higher than that at a pH similar to the pI regardless of the CS concentration. This finding could be attributable to the formation of a BSA/alginate complex. The evaluation of the interaction between BSA and alginate at different pH values by means rheological measurements confirmed this hypothesis. This approach may represent a promising way to devise a microcarrier system with appropriate size for targeting the Peyer's patches, with appropriate immobilization capacity, and suitable for the oral administration of peptidic drugs.

Alginates↗
PubMed2001

Calcium alginate microspheres of Bacillus subtilis.

Microspheres of Bacillus subtilis were prepared using sodium alginate. Some typical properties of microencapsulated systems, such as microorganism content, particle size, and germination time, were studied. Calcium alginate microspheres were obtained by the emulsification method, dripping into a solution of calcium salt. The conditions of the preparation steps were very soft to produce calcium alginate microspheres containing cells with no apparent changes in general biological properties. The hydrogel matrix provides protection without preventing communication with the surrounding medium.

Alginates↗
PubMed2005

Novel modulation of drug delivery using binary zinc-alginate-pectinate polyspheres for zero-order kinetics over several days: experimental design strategy to elucidate the crosslinking mechanism.

A Box-Behnken design was applied to mathematically establish whether different degrees of crosslinking were induced by Zn2+ and Ca2+ ions in polyspheres composed of alginate and/or pectin, and the model drug ibuprofen. Based on their different crystal structures and coordination numbers, a theoretical model was proposed demonstrating that Zn2+ ions preferentially crosslink alginate and pectin. In addition, the lower coordination number of Zn2+ (4-6) would significantly retard hydration of both polymers, as opposed to Ca2+ (7-9). The responses studied for 28 statistically derived polyspheres included drug encapsulation efficiency, physicomechanical behavior, and in vitro drug release potential. Single-tailed Student's t-tests on data generated for the encapsulation efficiencies, primary facture values, and rupture energies indicated that Zn2+ was statistically superior (p<0.05) in crosslinking alginate and pectin. Further textural analysis revealed a good correlation between the Brinell hardness number and fracture load, while an inverse relationship was found for matrix tensile strength. Viscosity studies demonstrated different in situ crosslinking thresholds for Zn2+. The Durbin-Watson statistic and correlation coefficient revealed that the quadratic regression function was highly accurate in predicting the responses. Using a generalized reduced gradient algorithm on dissolution values obtained after 2 hours (t2h) provided optimized solutions for achieving zero-order release extending from 2 hours to 7 days. Mathematical simulations projected drug release from 25 to 50 days.

Alginates↗
PubMed2001

Activated sludge immobilization using the PVA-alginate-borate method.

The PVA-alginate-borate method was used successfully to immobilize activated sludge. The optimum polyvinyl alcohol (PVA) concentration in the immobilized sludge was determined to be 10-12.5%. A minimal alginate of 1% in the beads was needed to prevent bead agglomeration. If the pH of the saturated boric acid was adjusted to 7.0 prior to allowing droplets of the mixture of PVA, alginate and sludge to enter the solution, a high level of sludge activity could be maintained in the beads formed. During the continuous operation of a fluidized bed reactor, with hydraulic retention time (HRT) in the range of 24-3 h (BOD loading from 0.176 to 0.766 kg/d/m3) and an aeration rate at 1.0 L/min, more than 90% of BOD5, NH4(+)-N and TKN were removed. The immobilized sludge exhibited satisfactory mechanical stability without apparent breakage.

Alginates↗
PubMed2001

Multiunit controlled-release diclofenac sodium capsules using complex of chitosan with sodium alginate or pectin.

This study explored the application of chitosan-alginate (CA) and chitosan-pectin (CP) complex films as drug release regulator for the preparation of multiunit controlled-release diclofenac sodium capsules. Pellets containing drug and microcrystalline cellulose, in a ratio of 3:5, were prepared in a fluidized rotary granulator. The pellets were coated with CA, CP, sodium alginate, pectin, and chitosan solutions. The pellets, equivalent to 75 mg drug, were filled into capsules. After 2 h of dissolution test in acidic medium, the amount of the drug released from any preparation was negligible. The pellets were further subject to pH 6.8 phosphate buffer More than 80% drug release at 12 h was observed with the uncoated pellets and those coated with sodium alginate, pectin or chitosan. Both 1% CA and 3% CP coated pellets exhibited drug release profiles similar to that of Voltaren SR75. It was found that approximately 60% and 85% of the drug were released at 12 and 24 h, respectively. Both Differential thermal analysis (DTA) and Fourier transform infrared spectroscopy (FTIR) analyses revealed complex formation between chitosan and these anionic polymers. It could be concluded that CA and CP complex film could be easily applied to diclofenac sodium pellets to control the release of the drug.

Alginates↗
PubMed1999

Delivery of recombinant gene products to the central nervous system with nonautologous cells in alginate microcapsules.

Somatic gene therapy using nonautologous recombinant cells immunologically protected with alginate microcapsules has been successfully used to treat rodent genetic diseases. We now report the delivery of recombinant gene products to the brain in rodents by implanting microencapsulated cells for the purpose of eventually treating neurodegenerative diseases with this technology. Alginate-poly-L-lysine-alginate microcapsules enclosing mouse C2C12 myoblasts expressing the marker gene human growth hormone (hGH) at 95+/-20 ng/million cells/hr were implanted into the right lateral ventricles of mice under stereotaxic guidance. Control mice were implanted similarly with nontransfected but encapsulated cells. Delivery of hGH to the different regions of the brain at various times postimplantation was examined. At 7, 28, 56, and 112 days postimplantation, hGH was detected at high levels around the implantation site and also at lower levels in the surrounding regions, while control mice showed no signal. Immunohistochemical staining of the implanted brains showed that on days 7, 56, and 112 postimplantation, hGH was localized in the tissues around the implantation site. Mice implanted with encapsulated but nontransfected cells showed no signal. Hence, the feasibility of using encapsulated nonautologous cells to deliver recombinant gene products to the brain for extended periods may allow the application of this technology to the treatment of neurodegenerative genetic disorders.

Alginates↗
PubMed2003

Liver tissue engineering within alginate scaffolds: effects of cell-seeding density on hepatocyte viability, morphology, and function.

Tissue engineering with three-dimensional biomaterials represents a promising approach for developing hepatic tissue to replace the function of a failing liver. Herein, we address cell seeding and distribution within porous alginate scaffolds, which represent a new type of porous biomaterial for tissue engineering. The hydrophilic nature of the alginate scaffold as well as its pore structure and interconnectivity enabled the efficient seeding of hepatocytes into the scaffolds, that is, 70-90% of the initial cells depending on the seeding method. Utilization of centrifugal force during seeding enhanced cell distribution in the porous scaffolds, consequently enabling the seeding of concentrated cell suspensions (>1 x 10(7) cells/mL). Cell density in scaffolds affected hepatocyte viability as judged by MTT assay. At a cell density of 0.28 x 10(6) cells/cm3 scaffold, the number of viable hepatocytes decreased to 33% of its initial value within 7 days, whereas at the denser cultures, 5.7 x 10(6) cells/cm3 scaffold and higher, the cells maintained higher viability while forming a network of connecting spheroids. In the high-density cellular constructs, hepatocellular functions such as albumin and urea secretion, and detoxification (cytochrome P-450 and phase II conjugating enzyme activities), remained high during the 7-day culture. Collectively, the results of the present study highlight the importance of cell density on the hepatocellular functions of three-dimensional hepatocyte constructs as well as the advantages of alginate matrices as scaffoldings.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2002

Alginic acid effect on carteolol ocular pharmacokinetics in the pigmented rabbit.

The effect of alginic acid addition to 1% or 2% carteolol solutions on the ocular penetration of the drug has been evaluated in the pigmented rabbit. During single dose studies, an increase in bioavailability ranging from 40% to 60% was observed in the aqueous humor and in the iris-ciliary body. During repeated dose studies, this increased ocular bioavailability of carteolol in the presence of alginic acid led to an equivalent concentration in the target tissue, although the dosage was only once a day compared with twice a day for the usual carteolol eyedrops. 14C-carteolol distribution studies demonstrated the binding of carteolol in pigmented ocular tissues. Thus, the presence of alginic acid as a new excipient supports a possible decrease in dosage regimen, while retaining sufficient ocular bioavailability to lower intraocular pressure.

Adrenergic beta-Antagonists↗
PubMed1998

Alginate gel culture allows the retention of extracellular matrix and follicular structure of rat thyroid tissue but does not lead to the formation of follicles by FRTL-5 cells.

Extracellular matrix (ECM) and basement membrane (BM) components were studied by immunohistological methods in native rat thyroid tissue, and in rat thyroid tissue and FRTL-5 cells cultured in a three-dimensional alginate bead system. In all three situations, the presence of collagen IV, laminin, perlecan, and fibronectin was demonstrated. There were marked differences between rat thyroid tissue and FRTL-5 cells in culture. Rat thyroid tissue maintained a follicular structure, whereas FRTL-5 cells did not form follicles. Rat thyroid cells multiplied more slowly than FRTL-5 cells and thyroglobulin (Tg) was visible in the follicular lumen, while in FRTL-5 cells Tg was only seen intracellularly. Tg iodination was much lower in FRTL-5 cells than in rat cells. In rat thyroid cells, positive staining for collagen IV, laminin, and perlecan was seen in thin membranes around individual follicles, and for fibronectin around groups of follicles. In FRTL-5 cells, these ECM/BM components could be identified, but were not organized into equally regular networks around groups of cells. These results demonstrate that of the two types of cells examined, primary cultures of rat thyroid cells in alginate beads maintain structural and functional similarities to native thyroid tissue and would therefore be suitable for future in vitro studies of thyroidal ECM/BM and their interrelationship with growth and function of this organ. FRTL-5 cells cultured in alginate beads show some functional, but not structural similarities to native thyroid tissue and so would be less valuable for use in such studies.

Alginates↗
PubMed1983

Evaluation of calcium alginate-tipped aluminum swabs transported in Culturettes containing ampules of 2-sucrose phosphate medium for recovery of Chlamydia trachomatis.

Two calcium alginate-tipped wire swab specimens were obtained from 94 men and 106 women attending a sexually transmitted disease clinic. One swab was extracted thoroughly in 2-sucrose phosphate (2SP) immediately after obtaining the specimen. The second swab was returned to the Culturette cylinder (Marion Scientific, Kansas City, MO), and the ampule containing 2SP was crushed to moisten the swab during transport to the laboratory. After receipt in the laboratory, the swab was removed from the Culturette and extracted into 2 mL of 2SP. Both specimens then were cultured for the presence of Chlamydia trachomatis in McCoy's cells. C. trachomatis was recovered from 22 of 94 men (23.4%); 16 isolates came from both the Culturette swabs and vials. Six isolates were recovered exclusively from vials. Of 106 women, 13 (12.3%) were positive for C. trachomatis. In five instances, both vials and swabs yielded C. trachomatis; the organism was recovered eight times from vials but not swabs. The 2SP transport system for the 200 specimens was superior to the Culturettes for the recovery of C. trachomatis (P less than 0.01). Based on our results, swab specimens taken for laboratory diagnosis of C. trachomatis should be extracted immediately after collection in a vial containing 2SP. In addition, experiments comparing swab fibers indicated that there was a trend indicating higher inclusion counts with rayon-tipped swabs, compared with those containing calcium alginate. Because of possible toxicity of substances in calcium alginate fibers for several organisms causing sexually transmitted disease, rayon-tipped swabs or swabs of other composition should be used.

Alginates↗
PubMed1995

Use of ultrasound to facilitate antibiotic diffusion through Pseudomonas aeruginosa alginate.

The effect of ultrasonic treatment of two pseudomonal alginate samples was studied by investigation of their rheological characteristics and interaction with tobramycin, piperacillin and ciprofloxacin. Whilst exposure to ultrasound at an amplitude of 20 microns for 8 min caused a significant decrease in viscosity of both alginates, molecular fragmentation, as demonstrated by PAGE and gel-permeation chromatography, was minimal. Antibiotic penetration was improved substantially however with sonication, leading to a 100% increase in tobramycin and piperacillin diffusion from the alginate compared with an untreated control polymer.

Alginates↗