Magnetic alginate beads for the targeted delivery of functional hydrophobic compounds

New composite alginate beads filled with Fe₃O₄ magnetic particles and Vaseline droplets containing the dissolved hydrophobic dye Sudan 3 are prepared. The structures of beads and Fe₃O₄ particles are studied with the aid of an optical microscope. The destruction of beads in an inhomogeneous magnetic field is investigated. The effects of the composition of beads and the magnitude of magnetic field on the release of hydrophobic components in the surrounding solution are analyzed. It is shown that the release of Sudan 3 due to the destruction of beads attains 75%.     

Formulation characterization and in vitro evaluation of acacia gum–calcium alginate beads for oral drug delivery systems

In the present work, new matrix bead formulations based on linear and branched polysaccharides have been developed using an ionic gelation technique, and their potential use as oral drug carriers has been evaluated. Using calcium chloride as a cross‐linking agent and sodium diclofenac (SD), as a model drug, acacia gum–calcium alginate matrix beads were formulated. The response surface methodology based on 3² factorial design was used as a statistical method to evaluate and optimize the effects of the biopolymers‐blend ratio and the concentration of calcium chloride on the particle size (mm), density (g/cm³), drug encapsulation efficiency (%), and the cumulative drug release after 8 hours (R_8h,%). The optimized beads with the highest drug encapsulation efficiency were examined for a drug‐excipients compatibility by powder X‐ray diffraction, differential scanning calorimetry, thermo‐gravimetric analysis, and Fourier transform‐infrared spectroscopy analyses. The swelling and degradation of the matrix beads were found to be influenced by the pH of medium. Higher degrees of swelling were observed in intestinal pH than in stomach pH. Accordingly, the drug release study showed that the amount of SD released from the acacia gum–calcium alginate beads was higher in intestinal pH than in stomach pH. Therefore, the in vitro drug release from the SD‐loaded beads appears to follow the controlled‐release (Hixson‐Crowell) pattern involving a case‐2 transport mechanism operated by swelling and relaxation of the polymeric blend matrix.     

Ionically crosslinked alginate/carboxymethyl chitin beads for oral delivery of protein drugs

Complex beads composed of alginate and carboxymethyl chitin (CMCT) were prepared by dropping aqueous alginate-CMCT into an iron(III) solution. The structure and morphology of the beads were characterized by IR spectroscopy and scanning electron microscopy (SEM). IR confirmed electrostatic interactions between iron(III) and the carboxyl groups of alginate as well as CMCT, and the binding model was suggested as a three-dimensional structure. SEM revealed that CMCT had a porous morphology while alginate and their complex beads had a core-layer structure. The swelling behavior, encapsulation efficiency, and release behavior of bovine serum albumin (BSA) from the beads at different pHs were investigated. The BSA encapsulation efficiency was fairly high (>90%). It was found that CMCT disintegrated at pH 1.2 and alginate eroded at pH 7.4 while the complex beads could effectively retain BSA in acid (>85%) and reduce the BSA release at pH 7.4. The results suggested that the iron(III)-alginate-CMCT bead could be a suitable polymeric carrier for site-specific protein drug delivery in the intestine.     

Hybrid alginate beads with thermal‐responsive gates for smart drug delivery

Polysaccharide‐based thermo‐responsive material was prepared by grafting PNIPAAm onto hybrid alginate beads, in which a biomineralized polyelectrolyte layer was constructed aiming to enhance the mechanical strength and ensure higher graft efficiency. XPS results demonstrated that the incorporation of PNIPAAm to the hybrid beads was successful, and the PNIPAAm‐grafted beads were more hydrophilic than the ungrafted ones as indicated by their swelling behavior. The drug release behaviors revealed that the grafted beads were both thermo‐ and pH‐sensitive, and the PNIPAAm existed in the pores of the alginate beads acted as the “on–off” gates: the pores of the beads were covered by the stretched PNIPAAm to delay the drug release at 25°C and opened to accelerate the drug release at 37°C because of the shrinking of PNIPAAm molecules. This paper would be a useful example of grafting thermo‐responsive polymers onto biodegradable natural polymer substrate. The obtained beads provide a new mode of behavior for thermo‐responsive “smart” polysaccharide materials, which is highly attractive for targeting drug delivery system and chemical separation. Copyright © 2010 John Wiley & Sons, Ltd.     

Preparation and evaluation of spore-specific affinity-augmented bio-imprinted beads

A novel, affinity-augmented, bacterial spore-imprinted, bead material was synthesized, based on a procedure developed for vegetative bacteria. The imprinted beads were intended as a front-end spore capture/concentration stage of an integrated biological detection system. Our approach involved embedding bead surfaces with Bacillus thuringiensis kurstaki (Bt) spores (as a surrogate for Bacillus anthracis) during synthesis. Subsequent steps involved lithographic deactivation using a perfluoroether; spore removal to create imprint sites; and coating imprints with the lectin, concanavalin A, to provide general affinity. The synthesis of the intended material with the desired imprints was verified by scanning electron and confocal laser-scanning microscopy. The material was evaluated using spore-binding assays with either Bt or Bacillus subtilis (Bs) spores. The binding assays indicated strong spore-binding capability and a robust imprinting effect that accounted for 25% additional binding over non-imprinted controls. The binding assay results also indicated that further refinement of the surface deactivation procedure would enhance the performance of the imprinted substrate.     

Preparation and property of layer-by-layer alginate hydrogel beads based on multi-phase emulsion technique

Layer-by-layer (LbL) alginate beads, which were prepared by multi-phase emulsion technique, had been fabricated via the ionic crosslinking between calcium ion (Ca²⁺) and the carboxylic group of alginate. The prepared beads were spherical, smooth-surfaced and non-aggregated. The SEM analysis displayed the LbL structure of the beads clearly. It had been demonstrated that the size of the beads was controllable and had a correlation with concentration of sodium alginate (SA) and CaCl₂, ratio of water phase and oil phase (W/O), stirring speed, pH value of the water phase, viscosity of SA as well as the temperature for solidification. Stability studies showed that the beads degraded slowly in simulated gastric fluid and simulated intestinal fluid but degraded sharply when they were moved to simulated colonic fluid. Cytotoxicity study by MTT assay indicated that the prepared beads are slightly toxic. It is hoped that this kind of novel beads could be used in pharmaceutical area and cell culture area.     

Preparation of alginate coated chitosan hydrogel beads by thermosensitive internal gelation technique

Chitosan hydrogel beads were successfully prepared by the method of thermosensitive internal gelation technique. The prepared beads were spherical, smooth-surfaced and non-aggregated with a diameter of 1.7–2.1 mm. The diameters of beads can be controlled and have a correlation with the initial drop size, the concentration of CaCl₂, alginate and the time of solidification. The bead is comprised of three parts, which are chitosan/glycerophosphate (CS/GP) hydrogel core, chitosan-alginate (CS/SA) gel layer in the middle and calcium-alginate gelatin capsules in outer layer. Swelling studies indicate that the beads can be stable in simulated gastric fluid. But the beads shrink sharply when removed to simulated intestinal fluid. Drug release behavior showed that release of ornidazole in the beads is much slower than in the CS/GP hydrogel.     

Comparison of different technologies for alginate beads production

This paper describes the results of the round robin experiment “Bead production technologies” carried out during the COST 840 action “Bioencapsulation Innovation and Technologies” within the 5th Framework Program of the European Community. In this round robin experiment, calcium alginate hydrogel beads with the diameter of (800 ± 100) μm were produced by the most common bead production technologies using 0.5–4 mass % sodium alginate solutions as starting material. Dynamic viscosity of the alginate solutions ranged from less than 50 mPa s up to more than 10000 mPa s. With the coaxial air-flow and electrostatic enhanced dropping technologies as well as with the JetCutter technology in the soft-landing mode, beads were produced from all alginate solutions, whereas the vibration technology was not capable to process the high-viscosity 3 % and 4 % alginate solutions. Spherical beads were generated by the electrostatic and the JetCutter technologies. Slightly deformed beads were obtained from high-viscosity alginate solutions using the coaxial airflow and from the 0.5 % and 2 % alginate solutions using the vibration technology. The rate of bead production using the JetCutter was about 10 times higher than with the vibration technology and more than 10000 times higher than with the coaxial air-flow and electrostatic technology. In memory of our colleague Stefan Rosinski     

New method for evaluation of heavy metal binding to alginate beads using pH and conductivity data

Extensive research has been conducted for removal and recovery of heavy metals from wastewater and industrial wastewater in recent years. Due to its low cost and high sorption efficiency, alginate was extensively investigated as a biosorbent. It is known that the sorption of metals to alginate is rate limited. However, the sampling in the beginning of experiments, from 30 seconds to few minutes, is very difficult, if not impossible. In this study, a nontraditional experimental method was used to determine the removal kinetics of metals for short time periods. A relationship among pH, conductivity, and metal concentration was established. It was shown that the sorption mechanism was ion exchange for all metals investigated in this study. A series of experiments was conducted to determine the ion exchange kinetics of different metals at varying pH conditions. Second order pseudo rate kinetics was shown to define the experimental findings well. Results also showed that the extent of exchange significantly reduced as the pH decreased. The selectivity of metal exchange to alginate beads was determined. It was observed that the extent of the ion exchange was greatest for Cu^{2 +} and lowest for Mn^{2 +} and Fe^{2 +}, following the order of Cu^{2 +} > Zn²⁺≅ Co^{2 +}≅ Ni²⁺ > Mn²⁺≅ Fe²⁺.     

Physico-chemical properties of alginate gel beads

Alginate gel beads are used in many applications as matrices for release or immobilisation. Until now, the parameters (such as type and concentration of cation, ionic strength and pH) of the beads formation solution in which the Na-alginate solution was dropped were not deeply studied. Therefore, in this paper, the gel formation of alginate beads and their behavior in demineralized water has been investigated carefully. The results obtained in the present study about the gel formation showed that (1) the type and the concentration of the cation play a determinant role in the gel formation phenomenon giving beads of different volumes and characteristics; (2) the weight and volume losses occurring in the ‘syneresis’ are essentially by water elimination; (3) NaCl, which gives the ionic strength of the beads formation solution, plays two roles: a competitor with calcium and a screen in the electrostatic repulsion; and (4) finally, the pH controls the gel formation process as regulator in the dissociation of the alginate and in the complexation of the calcium cations. A study by weight change dynamic analysis was also carried out. The results showed that the transfer of a bead from its formation solution into demineralized water provokes a modification of its volume, weight and stability. These results are important to understand the behavior of beads in their utilization medium.     

pH-responsive interpenetrating network hydrogel beads of poly(acrylamide)-g-carrageenan and sodium alginate for intestinal targeted drug delivery: synthesis, in vitro and in vivo evaluation

In the present work, we synthesized pH-responsive interpenetrating network (IPN) hydrogel beads of polyacrylamide grafted κ-carrageenan (PAAm-g-CG) and sodium alginate (SA) for targeting ketoprofen to the intestine. The PAAm-g-CG was synthesized by free radical polymerization followed by alkaline hydrolysis under nitrogen gas. The PAAm-g-CG was characterized by elemental analysis, FTIR spectroscopy and thermogravimetric analysis (TGA). The drug-loaded IPN hydrogel beads were prepared by simple ionotropic gelation/covalent crosslinking method. The amorphous nature of drug in the beads was confirmed by differential scanning calorimetry and X-ray diffraction studies. The spherical shape of the beads was confirmed by scanning electron microscopic analysis. The beads exhibited ample pH-responsive behavior in the pulsatile swelling study. The ketoprofen release was significantly increased when pH of the medium was changed from acidic to alkaline. The beads showed maximum of 10% drug release in acidic medium of pH 1.2, and about 90% drug release was recorded in alkaline medium of pH 7.4. Stomach histopathology of albino rats indicated that the prepared beads were able to retard the drug release in stomach leading to the reduced ulceration, hemorrhage and erosion of gastric mucosa.     

Characterization of invertase entrapped into calcium alginate beads

A solution of 10 g/L of sodium alginate (Satialgine® types used [Sanofi trademark]: SG800® and S1100® with manuronic/guluronic ratio of 0.5 and 1.2, respectively) containing invertase (0.08 g of protein/L) was dropped into 0.1 M CaCl₂ solution buffered at pH 4.0, 7.0, or 8.0. The beads were left to harden in CaCl₂ solution for 24 h. The high immobilization yield of 60% occurred with SG800 at pH8.0. The activity of soluble and insoluble invertase was measured against pH (2.8–8.0), sucrose concentration (4.5–45 mM), and temperature (30–60°C). Both forms presented an optimum pH of 4.6. However, the soluble invertase was stable at the overall pH interval studied, whereas insoluble invertase lost 30% of its original activity at pH > 5.0. At temperatures above 40°C, the insoluble form was more stable than the soluble one. The kinetic constants and activation energies (E _a ) for free invertase were K _M =41.2 mM, V _max=0.10 mg of TRS/(min · mL), and E _a 28 kJ/mol for entrapped invertase they were (K _M ) _ap =7.2 mM, (V _max) _ap =0.060 mg of TRS/(min · mL), and (E _a )_ap=24 kJ/mol.     

Biomineralized polysaccharide beads for dual-stimuli-responsive drug delivery

Biomineralized polysaccharide-coated alginate beads containing PNIPAAM were prepared. The resulting beads can be used as carriers for sustained pH/temperature-sensitive drug delivery. Characterizations using SEM, EDS, FTIR, and POM revealed that the beads were covered by the calcium-phosphate-mineralized alginate/chitosan membrane. The drug-release behavior was examined using indomethacin as a model drug, and the release profile of the developed materials was found to be responsive to pH and temperature. The release profile could be sustained under neutral conditions, indicating that the mineralized polysaccharide membrane could prevent the permeability of the encapsulated drug and reduce the drug release rate.     

Preparation and evaluation of uniform-sized molecularly imprinted polymer beads used for the separation of sulfamethazine

Uniform-sized molecularly imprinted polymer (MIP) beads were prepared using a one-step swelling and polymerization method. The obtained sulfamethazine (SMZ)-imprinted polymer showed high affinity and selectivity toward SMZ and other structurally related sulfonamides in acetonitrile or water-acetonitrile mobile phases, particularly in high aqueous systems. The column performance of the MIPs for SMZ and its analogues could be improved by elevating the column temperature and optimizing the flow rate. The hydrogen-bonding effect plays a significant role in the recognition process of SMZ-imprinted polymer systems in organic media, while the ion-exchange effect, as well as hydrophobic effect, dominates the retention mechanism in aqueous-rich media, in addition to shape recognition.     

Studies in the development of nateglinide loaded calcium alginate and chitosan coated calcium alginate beads

Nateglinide loaded alginate-chitosan beads were prepared by ionic gelation method for controlling the drug release by using various combinations of chitosan and Ca2+ as cation and alginate as anion. IR spectrometry, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry were used to investigate the physicochemical characteristics of the drug in the bead formulations. The calcium content in beads was determined by atomic absorption spectroscopy. The swelling ability of the beads in different media (pH 1.2, 4.5, 6.8) has been found to be dependent on the presence of polyelectrolyte complex of the beads and the pH of the media. The ability to release the Nateglinide was examined as a function of chitosan and calcium chloride content in the gelation medium. It is evident that the rate of drug release and its kinetics could be controlled by changing the chitosan and the calcium chloride concentrations. Calcium alginate beads released more than 95% of drug with in 8 h; whereas coated beads sustained the drug release and released only 75-80% of drug. The drug release mechanism analyzed indicates that the release follows either "anomalous transport" or "case-II transport".     

Properties of calcium-induced gel beads prepared with alginate and hydrolysates

Calcium-induced alginate gel beads (Alg-Ca) containing alginate hydrolysate, such as the guluronic acid block (GB), was prepared and the drug release profiles were investigated under simulated gastrointestinal conditions. The addition of GB to Alg-Ca altered its rheological properties. A model drug (hydrocortisone) was incorporated at 78% of its theoretical yield within the dried Alg-Ca containing 5% GB and it was gradually released from the beads in JP XIV 1st medium for disintegration test (pH 1.2), while it was rapidly released with disintegration of the gel matrix in JP XIV 2nd medium (pH 6.8). In contrast, for Alg-Ca containing GB and chitosan, disintegration was not observed in these media and the drug release rate was markedly different. These results demonstrate that the release profiles of drugs incorporated into Alg-Ca can be controlled by adding these polysaccharides.     

Gold and silver uptake and nanoprecipitation on calcium alginate beads

Calcium alginate beads were investigated for their biosorption performance in the removal of gold and silver from aqueous solutions. It was found that uptake capacities were significantly affected by the solution pH, with optimum pH values of 2 and 4 for gold and silver, respectively. Kinetic and isotherm experiments were carried out at the optimum pH. The maximum uptake capacities were 290 mg/g for Au and 52 mg/g for Ag. FTIR analysis indicated that both carboxylic and hydroxylic functional groups in alginate beads are involved in the metal binding and later reduction of gold (+3) and silver (+1) to gold (0) and silver (0). SEM and X-ray diffraction confirmed the formation of gold and silver nanoparticles.     

Inorganic–organic hybrid alginate beads with LCST near human body temperature for sustained dual‐sensitive drug delivery

In order to obtain dual‐stimuli‐responsive (temperature/pH) alginate beads that exhibit LCST close to human body temperature for sustained drug release applications, poly (NIPAAm‐co‐AAm) hydrogel (with LCST 37.5°C) were selected and associated with calcium alginate to prepare inorganic–organic hybrid biomineralized polysaccharide alginate beads via a one‐step method in this paper. Scanning electron microscopy (SEM) and energy dispersive X‐ray spectrometer (EDS) results demonstrated that calcium phosphate could not only be found in the surface but also in the cross‐section of biomineralized polysaccharide beads. Both equilibrium swelling and indomethacin release behavior were found to be pH‐ and thermo‐responsive. In addition, indomethacin release profile could be sustained with a inorganic–organic hybrid membrane: the release amount reached 96% within 4 hr for the unmineralized beads, while a drug release of only 64% obtained after subjecting the biomineralized polysaccharide beads to the same treatment. These results indicate that the biomineralized polysaccharide membrane could prevent the permeability of the encapsulated drug and reduce the drug release rate effectively. The studied system has the potential to be used as an effective smart sustainable delivery system for biomedical applications. Copyright © 2008 John Wiley & Sons, Ltd.     

Removal of some nitrophenol contaminants using alginate gel beads

Biopolymers such as alginates are commonly used to remove the cationic contaminants from wastewaters. The major component of the alginate is the alginic acid, a linear, binary heteropolymer of β-d-mannuronate and -l-guluronate residues. In this study the fundamental aspects in the preparation of alginate beads and the effects of salt, sodium alginate concentrations and two cationic surfactants (dodecyltrimethylammonium bromide, cetyltrimethylammonium bromide) on the domains of binding isotherms were investigated. The alginate cross-link complexes with metal ions can exist either as homogeneous clear solutions or precipitates or as spherical beads. The applicability of the calcium and calcium–iron alginate gel beads for removal of some nitrophenols from aqueous solutions was studied. The sorption and kinetic experiments were conducted under different values of pH, initial concentration of nitrophenols and the amount of alginate gel beads. The removal efficiency of contaminant increases with the increasing of the pH and the quantity of alginate beads and decreases with the increasing of initial contaminant concentration. The uptake of nitrophenols occurs rapidly in the first 12 h, followed by a slow process that takes about 72 h. According to the egg-box model of gelation mechanism the cavities formed in the alginate gel capture the cationic contaminants. The adsorption equilibrium data obtained for nitrophenols derivatives at various pH and initial solid sorbent amount were applied to the two classical models, i.e. Langmuir and Freundlich, and the isotherm parameters were calculated.     

Entrapment of ethyl vanillin in calcium alginate and calcium alginate/poly(vinyl alcohol) beads

Electrostatic extrusion was applied to the encapsulation of 3-ethoxy-4-hydroxybenzaldehyde (ethyl vanillin) in calcium alginate and calcium alginate/poly(vinyl alcohol) beads. The calcium alginate/poly(vinyl alcohol) hydrogel spheres were formed after contact with the cross-linker solution of calcium chloride, followed by the freeze-thaw method for poly(vinyl alcohol) gel formation. The entrapment of aroma in beads was investigated by FTIR and thermal analysis (thermogravimetry/differential thermal gravimetry; TGA/DTG). The mass loss in the temperature range of 150?C300°C is related to degradation of the matrix and the release of ethyl vanillin. According to the DTG curve, the release of ethyl vanillin occurs at about 260°C. TGA measurements of the stored samples confirmed that formulations were stable for a period of one month. FTIR analysis provides no evidence for chemical interactions between flavour and alginate that would alter the nature of the functional groups in the flavour compound.