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.     

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".     

Preparation and properties of thermosensitive hydrogel microcapsules

Temperature-sensitive hydrophilic gel microcapsules have been newly prepared. That is, poly ( -lysineisopropylamide–terephthalic acid) microcapsules containing water have been obtained by an interfacial polymerization at a water/oil interface between -lysineisopropylamide and terephthaloyldichloride. The microcapsule changes its size between 33 and 35°C. Under 33°C, the microcapsules are fully spherical and can be redispersed in distilled water, while are aggregated above 35°C. The microcapsules, which are observed to show aggregation above 33°C, can be redispersed by decreasing temperature within a few second. The thermosensitive morphological changes of the microcapsules are thus reversible. Also, it has been shown that the permeability of sodium chloride through the microcapsule membrane changes remarkably between 33 and 35°C, while it is kept almost constant independent of temperature between 25 and 33°C or between 35 and 55°C. The permeability of solutes is higher under 33°C than that above 35°C. Such thermosensitive properties result from the fact that the polymer membrane has isopropylamide groups. That is, -lysineisopropylamide has a chemical structure similar to N-isopropylacrylamide, the polymer of which, poly (N-isopropylacrylamide), is a thermosensitive hydrogel having its phase transition temperature around 33°C.     

Preparation of aqueous gel beads coated by lipid bilayers

Novel giant liposome microcapsules have been fabricated based on aqueous gel cores encapsulated with a lipid bilayer. The method involves templating of lipid-stabilised water-in-oil emulsions after gelling the aqueous phase with a suitable hydrocolloid.     

The drug release profile from calcium-induced alginate gel beads coated with an alginate hydrolysate

Calcium-induced alginate gel bead (Alg-Ca) coated with an alginate hydrolysate (Alg), e.g. the guluronic acid block (GB) was prepared and the model drug, hydrocortisone release profiles were investigated under simulated gastrointestinal conditions. Their molecular weights were one sixth or one tenth that of Alg and the diffraction patterns of the hydrolysates resembled that of Alg. The drug release rate from Alg-Ca coated with GB apparently lowered than that of Alg-Ca (coating-free) in the gastric juice (pH1.2). And the coating did not resist the disintegration of Alg-Ca in the intestinal juice (pH 6.8) and the gel erosion accelerated the drug release. On the other hand, for the coated Alg-Ca containing chitosan, the drug release showed zero-order kinetics without rapid erosion of Alg-Ca. The drug release rate from Alg-Ca was able to be controlled by the coating and modifying the composition of the gel matrix.     

Bactericidal activity of hydrogel beads based on N,N,N-trimethyl chitosan/alginate complexes loaded with silver nanoparticles

Polysaccharide-based composite materials (beads) containing silver nanoparticles (AgNPs) were successfully prepared. Hydrogel beads acted as an efficient vehicle for Ag⁺ delivery. Beads promoted the AgNPs protection and inhibited their aggregation. Antimicrobial assays showed that the beads/AgNPs concentration can be modulated to deliver an amount of Ag⁺ necessary for kill Escherichia coli cells.     

Effect of organic and inorganic acids on chitosan/glycerophosphate thermosensitive hydrogel

The influence of organic and inorganic acids on chitosan/glycerophosphate (CS/GP) hydrogel has been investigated by dissolving chitosan in different acids. The results of gelation showed that all of the chitosan dissolved in monovalent acid solutions (i.e., formic, acetic, propionic, butyric, isobutyric, lactic, nitric, hydrochloric, and chloroacetic acid), when neutralized by GP solution, could transform into hydrogel after 2–5 min at 37 °C, while those dissolved in multivalent acids failed in gel formation. The inner structures of CS/GP hydrogels prepared with monovalent acids depended on the ionic strength and chain length of acids. Morphological examination by scanning electron microphotography demonstrated that large pores occurred during the gel-forming process, and the aperture size was also related to different acids. The cytotoxicity studies indicated that CS/GP systems prepared by dissolving chitosan in tested acids except chloroacetic acid were nontoxic to mouse embryonic fibroblasts and Hela cells.     

Preparation of chitosan/alginate microcapsules by high-voltage electrostatic method

Chitosan and sodium alginate have the opposite charges; they can become a gelatin by the electrostatic attraction, High-voltage electrostatic droplet generator method was used to prepare chitosan-sodium alginate microcapsule. Multi-layer chitosan-sodium alginate microcapsule was prepared through layer-by-layer self-assembly, and the morphology was investigated. In addition, the release property of ofloxacin in microcapsules was studied by UV-Vis microscopy under different conditions such as pH value, layer number, etc. The results showed that the prepared microcapsules have a smooth surface with average particle size about 100 μm. The result of controlled release indicated that the prepared microcapsules are pH-independent, and the rate of release decreased when the layer number increases.     

非共价键交联海藻酸钠水凝胶的制备与性能

天然多糖海藻酸钠制备的水凝胶具有优越的生物相容性和生物组织相似性,作为生物医用材料在药物控制释放、组织工程支架、抗菌材料及创伤敷料等领域发挥着越来越大的作用。本文在介绍海藻酸钠物化性质的基础上,重点综述了非共价键交联(静电作用、氢键、范德华力、亲疏水作用等)海藻酸钠水凝胶的制备方法以及性能表征方法,最后讨论了制备方法及性能表征研究中的一些需要解决的问题。     

Characteristics and antioxidant activity of catechin-loaded calcium pectinate gel beads prepared by internal gelation

Catechin-loaded calcium pectinate gel beads prepared by internal gelation were characterized for their catechin entrapment efficiency and release behavior. The entrapment efficiency was higher when the beads were prepared with a lower catechin-to-pectin ratio, shorter gelling time, higher pectin concentration, and lower acetic acid concentration. The entrapment efficiency was much higher under all tested conditions, when the beads were prepared by internal gelation instead of external gelation. The catechin release was slower for the beads prepared with lower catechin-to-pectin ratio, longer gelling time, and higher concentrations of pectin and acetic acid in both simulated gastric and intestinal fluids. Antioxidant power of catechin was effectively maintained in alkaline simulated intestinal fluid when catechin was entrapped within the beads, compared to cases where it was not entrapped, indicating that the beads can protect catechin molecules from the alkaline environment and release them in a sustained fashion.     

Electrophoretic extraction and analysis of DNA from chitosan or poly-l-lysine-coated alginate beads

Alginate beads containing entrapped DNA were produced using both external and internal calcium sources, and coated with chitosan or poly-l-lysine membranes. The beads were assayed with DNase nuclease to determine formulation conditions offering the highest level of DNA protection fromnucleic acid hydrolysis, simulating gastrointestinal exposure. A method was developed to extract and assay intracapsular DNA through a modified agarose electrophoresis system. Both external and internally gelled beads were permeable to DNase (M_w=31 kDa), indicated by the absence of DNA after nuclease exposure. At low levels of DNase exposure, coated high guluronic content alginate beads offered a higher level of DNA protection compared with coated beads with low guluronic alginate. No apparent correlation was found with chitosan membrane molecular weight and degree of deacetylation; however, increasing poly-l-lysine molecular weight appeared to increase DNase exclusion from beads. At elevated levels of DNase exposure, DNA hydrolysis was evident within all coated beads with the exception of those coated with the highest molecular weight poly-l-lysine (M_w=197.1 kDa), which provided almost total nuclease protection. Optimal combination then for DNA protection from nucleases is a high guluronic alginate core, coated with high molecular weight poly-l-lysine.     

The effects of pH and ionic strength on fulvic acid uptake by chitosan hydrogel beads

The objective of this work is to investigate the effects of pH and ionic strength on the adsorption capacity for fulvic acid (FA) by chitosan hydrogel beads. The results indicated that the sorption amount increased with decreasing pH and increasing ionic strength concentration. The sorption isotherms were well described by using non-linear Langmuir, Freundlich and Redliche–Peterson equation. The adsorption kinetics of FA onto chitosan hydrogel beads could be described by pseudo-second-order rate model. The extent of FA removal in the presence of other ions decreases in the order Ca²⁺ > Mg²⁺ > Na⁺ ≈ K⁺ and Cl⁻ > NO₃⁻ > CO₃²⁻. FTIR along with XPS analyses revealed the amine groups on the beads were involved in the sorption of FA and the organic complex between the protonated amino groups and FA was formed after FA uptake. Sorption mechanisms including electrostatic interaction and surface complexation were found to be involved in the complex sorption of FA on the chitosan hydrogel beads.     

Synthesis of silver nanoflakes on chitosan hydrogel beads and their antimicrobial potential

Abstract

The present study involves the fabrication of CH and CH-Ag hydrogel beads and the investigation of the antimicrobial properties. The beads were fabricated using a simple coacervation method. The successfully synthesized beads were characterized by UV-Vis and FTIR. The surface morphology, shape and diameter of the samples were determined by optical microscopy and SEM. The antimicrobial activities were determined against potential human pathogens including bacterial and fungal species. Our results demonstrated that beads can be utilized as potential materials for use in biomedical approaches including delivery systems and tissue engineering applications to prevent microbial contamination and to inhibit the growth of microorganisms.     

Preparation and controlled degradation of oxidized sodium alginate hydrogel

Degradation is often a critical property of materials utilized in tissue engineering. Although alginate, a naturally derived polysaccharide, is an attractive material due to its biocompatibility and ability to form hydrogels, its slow and uncontrollable degradation can be an undesirable feature. In this study, the degradation behavior of hydrogel based on oxidized sodium alginate (OSA) crosslinked with Ca²⁺ was studied in phosphate buffer solution (PBS, pH = 7.4) and Tris-(hydroxymethyl) aminomethane–HCl (Tris–HCl, pH = 7.4) at 37 °C. The degradation behavior of OSA hydrogels with different degrees of oxidation was evaluated as a function of degradation time by monitoring the changes of molecular weight and weight loss. It was found that the degradation behavior relied heavily on the degree of oxidation and the surrounding medium. This result indicates that the degradation rates of OSA hydrogels can be controlled by changing the degree of oxidation.     

Preparation of calcium alginate microgel beads in an electrodispersion reactor using an internal source of calcium carbonate nanoparticles

An electrodispersion reactor has been used to prepare calcium alginate (Ca-alginate) microgel beads in this study. In the electrodispersion reactor, pulsed electric fields are utilized to atomize aqueous mixtures of sodium alginate and CaCO3 nanoparticles (dispersed phase) from a nozzle into an immiscible, insulating second liquid (continuous phase) containing a soluble organic acid. This technique combines the features of the electrohydrodynamic force driven emulsion processes and externally triggered gelations in microreactors (the droplets) ultimately to yield soft gel beads. The average particle size of the Ca-alginate gels generated by this method changed from 412 +/- 90 to 10 +/- 3 microm as the applied peak voltage was increased. A diagram depicting structural information for the Ca-alginate was constructed as a function of the concentrations of sodium alginate and CaCO3 nanoparticles. From this diagram, a critical concentration of sodium alginate required for sol-gel transformation was observed. The characteristic highly porous structure of Ca-alginate particles made by this technique appears suitable for microencapsulation applications. Finally, time scale analysis was performed for the electrodispersion processes that include reactions in the microreactor droplets to provide guidelines for the future employment of this technique. This electrodispersion reactor can be used potentially in the formation of many reaction-based microencapsulation systems.     

Preparation and evaluation of berberine alginate beads for stomach-specific delivery

The purpose of this research was to prepare floating calcium alginate beads of berberine for targeting the gastric mucosa and prolonging their gastric residence time. The floating beads were prepared by suspending octodecanol and berberine in sodium alginate (SA) solution. The suspension was then dripped into a solution of calcium chloride. The hydrophobic and low-density octodecanol enhanced the sustained-release properties and floating ability of the beads. The bead formulation was optimized for different weight ratios of octodecanol and SA and evaluated in terms of diameter, floating ability and drug loading, entrapment and release. In vitro release studies showed that the floating and sustained release time were effectively increased in gastric media by addition of octodecanol. In vivo studies with rats showed that a significant increase in gastric residence time of beads had been achieved.     

Preparation and drug retention of biodegradable chitosan gel beads.

Chitosan (CS) gel beads containing drug could be prepared in amino acid solutions of pH about 9, despite the requirement for a pH above 12 for gelation in water. This phenomenon was observed not only in amino acid solutions but also in solutions of compounds having amino groups. A solute concentration of more than 10% was required for preparation of gel beads at pH 9. Gelation of the CS beads required about 25 to 40 min, depending on the species of amino acid. Lidocaine hydrochloride (LC) as a model drug was retained in the beads to about 20 to 35% of the theoretical total amount, despite being a water-soluble drug. The release of LC from the CS gel beads was prolonged. The release pattern was not affected by the species of amino acid or CS, or the preparation time.     

基于埃洛石的载药凝胶小球的制备及性能研究

采用离子凝胶法制备了一种新的壳聚糖-g-聚丙烯酸/埃洛石/海藻酸钠(CTS-g-PAA/HT/SA)凝胶小球。研究了HT含量对载药凝胶小球的溶胀性、包封效率和释放性能等的影响;同时也讨论了凝胶小球的pH敏感性和双氯芬酸钠(DS)的释放行为。结果表明:HT含量对载药凝胶小球的溶胀率、包封效率和累积释放率有明显的影响,在HT含量为30%时,溶胀率、包封效率和12h累积释放率分别达到32.84%、91.07%和100%;另外,载药凝胶小球具有较好的pH敏感性;在pH=2.1的释放介质中DS几乎不释放,而在pH=6.8的释放介质中缓慢释放;DS释药机理为溶胀控释。