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1.
Effect of alginate composition and purity on alginate microspheres   总被引:1,自引:0,他引:1  
BACKGROUND: Alginate is commonly used to microencapsulate islets in experiments with islet allografts and xenografts for the treatment of Type I diabetes. The purpose of the present study is to determine the effects of alginate composition and purity on the morphology and size of microspheres. METHODS: Microcapsules produced with the impure alginate types, medium-viscosity high-guluronic acid (IMVG), low-viscosity high-G (ILVG), low-viscosity high-mannuronic acid (ILVM) and medium-viscosity high-M (IMVM) were compared with one another and others generated with a highly purified LVM (HPLVM) alginate. Droplets of 1.5% alginate from an air-syringe pump were gelled in 1.1% CaCl2 solution. While leaving the alginate pressure and needle recess constant, the air-jacket pressure was varied between 9.5-10.5 PPSI to enhance stable microcapsule generation and different batches of microbeads were made from each alginate type. RESULTS: The sizes of the high-guluronic acid alginate microbeads were consistently bigger than those of the corresponding high-mannuronic acid alginate beads at all air-jacket settings. At the optimal air-jacket pressure of 9.0 PPSI, the mean+SD diameter of the IMVG microbeads was 780 + 20 microm, while that of IMVM was 607 + 44 microm (p < 0.0001, n=30). Similarly, the mean ILVG microbead diameter was 816+28 microm compared to 656+26 microm for ILVM capsules (p<0.0001, n=30). Less polymorphism was found with the HPLVM microspheres than with the ILVM microbeads. CONCLUSION: Highly purified high-mannuronic acid alginate will provide smaller, spherical microcapsules suitable for islet cell transplantation.  相似文献   

2.
Purpose: The purpose of this study was to determine the roles of alginate composition and gelling cations on bead swelling, which affects its durability.

Method: Using a 2-channel droplet generator, microspheres were generated with 1.5% solutions of low viscosity high-mannuronic acid (LVM), medium viscosity high-mannuronic acid (MVM), low viscosity high-guluronic acid (LVG) and medium viscosity high-guluronic acid (MVG) alginate. They were gelled by cross-linking with 1.1% solution of either BaCl2 or CaCl2. The diameters of the microbeads were measured and recorded on day 0. The microbeads were subsequently washed and incubated in saline at 37°C for 2 weeks with size assessment every 2 days. The data were normalized by calculation of the percentage change from control (day 0) for all groups of microbeads.

Results: Diameters of all beads were between 550–700 microns on day 0. Viscosity had no effect on swelling of Ba++- and Ca++-alginate microbeads. Ca++-alginate microbeads were more prone to swelling than the corresponding Ba++-alginate beads. High G-Ba++ beads had only a modest increase in size over time, in contrast to the high M-Ba++.

Conclusion: Alginate composition and the gelling cation have significant effects on bead swelling.  相似文献   

3.
PURPOSE: The purpose of this study was to determine the roles of alginate composition and gelling cations on bead swelling, which affects its durability. METHOD: Using a 2-channel droplet generator, microspheres were generated with 1.5% solutions of low viscosity high-mannuronic acid (LVM), medium viscosity high-mannuronic acid (MVM), low viscosity high-guluronic acid (LVG) and medium viscosity high-guluronic acid (MVG) alginate. They were gelled by cross-linking with 1.1% solution of either BaCl2 or CaCl2. The diameters of the microbeads were measured and recorded on day 0. The microbeads were subsequently washed and incubated in saline at 37 degrees C for 2 weeks with size assessment every 2 days. The data were normalized by calculation of the percentage change from control (day 0) for all groups of microbeads. RESULTS: Diameters of all beads were between 550-700 microns on day 0. Viscosity had no effect on swelling of Ba++- and Ca++-alginate microbeads. Ca++-alginate microbeads were more prone to swelling than the corresponding Ba++-alginate beads. High G-Ba++ beads had only a modest increase in size over time, in contrast to the high M-Ba++. CONCLUSION: Alginate composition and the gelling cation have significant effects on bead swelling.  相似文献   

4.
Effect of alginate composition and gelling cation on micro-bead swelling   总被引:1,自引:0,他引:1  
PURPOSE: The purpose of this study was to determine the roles of alginate composition and gelling cations on bead swelling, which affects its durability. METHOD: Using a 2-channel droplet generator, microspheres were generated with 1.5% solutions of low viscosity high-mannuronic acid (LVM), medium viscosity high-mannuronic acid (MVM), low viscosity high-guluronic acid (LVG) and medium viscosity high-guluronic acid (MVG) alginate. They were gelled by cross-linking with 1.1% solution of either BaCl2 or CaCl2. The diameters of the micro-beads were measured and recorded on day 0. The micro-beads were subsequently washed and incubated in saline at 37 degrees C for 2 weeks with size assessment every 2 days. The data were normalized by calculation of the percentage change from control (day 0) for all groups of micro-beads. RESULTS: Diameters of all beads were between 550 and 700 microm on day 0. Viscosity had no effect on swelling of Ba++- and Ca++-alginate micro-beads. Ca++-alginate micro-beads were more prone to swelling than the corresponding Ba++-alginate beads. High G-Ba++ beads had only a modest increase in size over time, in contrast to the high M-Ba++. CONCLUSION: Alginate composition and the gelling cation have significant effects on bead swelling.  相似文献   

5.
In this study, alginate microspheres containing BCG were prepared at a diameter of ~10?µm by emulsification–internal gelation of an alginate–BCG solution dispersed in olive oil using a high rate speed stirrer. The stability of BCG was assayed at 4°C showing that the encapsulated BCG was more stable than free BCG at least for 5 weeks; however, BCG in sodium alginate solution was not stable at all. On the other hand, the studies using media with different pH (1.2, 4.4, 6.2, 6.8 and 7.5) have demonstrated that the alginate microspheres are stable in acidic medium for upto 1.5?h without any sign of disintegration. Moreover, BCG incorporated in alginate microspheres demonstrated an almost 9-fold increase in viable bacilli in simulated gastric fluid (SGF) after 1.5?h in comparison with free BCG.  相似文献   

6.
In this study, chitosan-coated alginate microspheres were prepared by the ionic complexation of alginate and chitosan biopolymers to use in embolization and/or chemoembolization studies. Biopolymeric microspheres were prepared by the ionic gelation technique of alginate with a suitable divalent cation (i.e. CaCl2) in a suspension medium composed of mineral oil and petroleum ether including emulsifier (i.e. Tween-80) and then obtained microspheres were coated with chitosan in an aqueous chitosan solution while the medium was magnetically stirred. The obtained microspheres are in the size range of 100–400?µm and they can be prepared as required by changing the preparation conditions (i.e. stirring rate, concentration of biopolymers, molecular weight and concentration of chitosan, etc.). In the in vivo studies, New Zealand rabbits were used as the test animals. Both complete and partial embolization of the kidney were achieved by using the microspheres. The renal angiograms obtained before/after embolization and the histopathological observations showed the feasibility of the chitosan-coated alginate microspheres as an alternative embolization and/or chemoembolization agent.  相似文献   

7.
Mitomycin-C loaded and chitosan-coated alginate microspheres were prepared for use in chemoembolization studies. In this respect, first alginate microspheres were prepared by using a spraying method using an extrusion device with a small orifice and following suspension cross-linking in an oil phase. Chitosan-coating onto the alginate microspheres was achieved by polyionic complex formation between alginate and chitosan. CaCl2 was used as a cross-linker for alginate microspheres. The obtained chitosan-coated alginate microspheres were spherical shaped and ~100–400?µm average size. The microspheres were evaluated based on their swellability and the swelling ratio was changed between 50–280%. CaCl2 concentration, stirring rate, chitosan molecular weight, chitosan concentration and time for coating with chitosan were selected as the effective parameters on microsphere size and swelling ratio. Equilibrium swellings were achieved in ~30?min. On the other hand, chitosan molecular weight, chitosan concentration and time for coating with chitosan were found as the most effective parameters on both drug loading ratio and release studies. Maximum drug loading ratio of 65% was achieved with high molecular weight (HMW) chitosan, highest chitosan concentration (i.e. 1.0% v/v) and shortest time for coating with chitosan (i.e. 1?h) values.  相似文献   

8.
Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases.

Materials and Methods: The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30?min, and after 10?min of ultraviolet A irradiation.

Results: Eleven eyes of eleven patients with progressive keratoconus (n?=?10) and iatrogenic corneal ectasia (n?=?1) were included in this study. The mean thinnest pachymetric measurements were 391.82?±?30.34?µm (320–434?µm) after de-epithelialization of the cornea, 435?±?21.17?µm (402–472?µm) following 30?min instillation of isotonic riboflavin solution without dextran and 431.73?±?20.64?µm (387–461?µm) following 10?min of ultraviolet A irradiation to the cornea.

Conclusion: Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.  相似文献   

9.
Abstract

There is a growing interest in using proteins as therapeutics agents. Unfortunately, they suffer from limited stability and bioavailability. We aimed to develop a new delivery system for proteins. ALP, a model protein, was successfully encapsulated in the physically cross-linked sodium alginate/hydroxypropylcellulose (ALG-HPC) hydrogel microparticles. The obtained objects had regular, spherical shape and a diameter of ~4?µm, as confirmed by optical microscopy and SEM analysis. The properties of the obtained microbeads could be controlled by temperature and additional coating or crosslinking procedures. The slow, sustained release of ALP in its active form with no initial burst effect was observed for chitosan-coated microspheres at pH?=?7.4 and 37?°C. Activity of ALP released from ALG/HPC microspheres was confirmed by the occurance of effectively induced mineralization. SEM and AFM images revealed formation of the interpenetrated three-dimensional network of mineral, originating from the microbeads’ surfaces. FTIR and XRD analyses confirmed formation of hydroxyapatite.  相似文献   

10.
5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47?±?11 and 67?±?12?µg 5-FU?mg?1 microspheres and the percentage of entrapment efficiency was between 52?±?12 and 74?±?13. Microspheres were of small size (average diameter: 0.9?±?0.4–1.4?±?0.8?µm microspheres without drug; 1.1?±?0.5–1.7?±?0.9?µm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger Tg. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of Tg of the polymer of the microspheres. The presence of 5-FU did not modify the Tg values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28–129?h) was in the order PLA?>?PLGA 75/25?>?PLGA 50/50. A burst effect (17–20%) was observed during the first hour and then a period of constant release rate (3.52?±?0.82–1.46?±?0.26?µg 5-FU?h?1 per milligram of microspheres) up to 8 or 13?h, depending on the polymer, was obtained.  相似文献   

11.
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?µm 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.  相似文献   

12.
Abstract

Calcium alginate microbeads have been widely used in tissue engineering application, due to their excellent biocompatibility, biodegradability, enhanced mechanical strength and toughness. Bone powder containing abundant hydroxylapatite, type I collagen and growth factors such as BMP2 and BMP4, possesses good osteoinductive activity. Herein, a hybrid calcium alginate/bone powder microbead was therefore prepared. Afterwards, different seeding density of adipose-derived stem cells (ADSCs) in these hybrid microbeads was discussed systematically for further in vitro expansion. Optimised microbeads suitable for in vitro expansion and differentiation of ADSCs were prepared using the droplet method under overall considering suitable concentrations of calcium alginate and calcium chloride as well as the density of bone powder through an orthogonal experiment. The results showed that the concentration of sodium alginate had the most influence on inside mass transfer and mechanical strength of the hybrid microbeads, secondly the calcium chloride, then the density of bone powder. The hybrid microbeads could be optimally performed while the concentrations of sodium alginate and calcium chloride were 2.5% and 4.5%, as well as 5.0?mg/mL bone powder, respectively. Live/Dead assay showed that the expanded ADSCs differentiated well with an initial embedding density of 5?×?106 cells/mL.  相似文献   

13.
This study investigated the formative process of alginate microspheres produced using an emulsification technique. The alginate microspheres were produced by cross-linking alginate globules dispersed in a continuous organic phase using various calcium salts: calcium chloride, calcium acetate, calcium lactate and calcium gluconate. The size, shape, drug content and Ca2+ content of the microspheres were evaluated. The tack, viscosity and pH of the calcium salt solution and percentage of Ca2+ partitioned into the organic phase were determined. Microscopic examination of the test emulsion at various stages of the emulsification process was also carried out. The propensity of cross-linking reaction was found to be dependent on successful collision between alginate and calcium salt globules. Examination of the characteristics of microspheres indicated that the formed microsphere was a resultant product of alginate globule clustering. The growth propensity of microspheres was promoted by the higher rate and extent of cross-linkage which was governed by the pH, tack and/or Ca2+ content of the cross-linking solution, as well as the dissociation constant and diffusivity of the calcium salt. Overall, the amount of free Ca2+ cross-linked with alginate in the formed microspheres was in the following order: calcium acetate > calcium chloride + calcium acetate > calcium chloride + calcium gluconate; calcium chloride + calcium lactate > calcium chloride. In microencapsulation by emulsification, the mean size of the microspheres produced can be modified by varying the tack, pH and Ca2+ content of the cross-linking solution and through the use of a combination of calcium salts. The shape of the microspheres produced was, nonetheless, unaffected by the physicochemical properties of the cross-linking solution.  相似文献   

14.
《Journal of drug targeting》2013,21(10):831-841
Microencapsulation of a hydrophilic active (gentamicin sulphate (GS)) and a hydrophobic non-steroidal anti-inflammatory drug (ibuprofen) in alginate gel microparticles was accomplished by molecular diffusion of the drug species into microparticles produced by impinging aerosols of alginate solution and CaCl2 cross-linking solution. A mean particle size in the range of 30–50 µm was measured using laser light scattering and high drug loadings of around 35 and 29% weight/dry microparticle weight were obtained for GS and ibuprofen respectively. GS release was similar in simulated intestinal fluid (phosphate buffer saline (PBS), pH 7.4, 37°C) and simulated gastric fluid (SGF) (HCl, pH 1.2, 37°C) but was accelerated in PBS following incubation of microparticles in HCl. Ibuprofen release was restricted in SGF but occurred freely on transfer of microparticles into PBS with almost 100% efficiency. GS released in PBS over 7?h, following incubation of microparticles in HCl for 2?h was found to retain at least 80% activity against Staphylococcus epidermidis while Ibuprofen retained around 50% activity against Candida albicans. The impinging aerosols technique shows potential for producing alginate gel microparticles of utility for protection and controlled delivery of a range of therapeutic molecules.  相似文献   

15.
The combination of protein-coated graphene oxide (GO) and microencapsulation technology has moved a step forward in the challenge of improving long-term alginate encapsulated cell survival and sustainable therapeutic protein release, bringing closer its translation from bench to the clinic. Although this new approach in cell microencapsulation represents a great promise for long-term drug delivery, previous studies have been performed only with encapsulated murine C2C12 myoblasts genetically engineered to secrete murine erythropoietin (C2C12-EPO) within 160?µm diameter hybrid alginate protein-coated GO microcapsules implanted into syngeneic mice. Here, we show that encapsulated C2C12-EPO myoblasts survive longer and release more therapeutic protein by doubling the micron diameter of hybrid alginate-protein-coated GO microcapsules to 380?µm range. Encapsulated mesenchymal stem cells (MSC) genetically modified to secrete erythropoietin (D1-MSCs-EPO) within 380?µm-diameter hybrid alginate-protein-coated GO microcapsules confirmed this improvement in survival and sustained protein release in vitro. This improved behavior is reflected in the hematocrit increase of allogeneic mice implanted with both encapsulated cell types within 380?µm diameter hybrid alginate-protein-coated GO microcapsules, showing lower immune response with encapsulated MSCs. These results provide a new relevant step for the future clinical application of protein-coated GO on cell microencapsulation.  相似文献   

16.
Microcapsules for enzyme immobilization were successfully fabricated via interfacial cross-linking of poly(ethyleneimine) (PEI). A method based on laminar jet break-up technique using a commercial instrument developed to produce alginate beads is reported for the first time for production of PEI microcapsules. The diameter, wall thickness and pore size of membranes were obtained from confocal laser scanning microscopy by labelling PEI and proteins. The composition of membranes was analysed by elemental analysis. Larger microcapsules (ca 200?µm diameter) were obtained with the encapsulation device. In comparison, the emulsion method produced smaller capsules (ca 20?µm diameter) but with a wider size distribution. Encapsulation efficiency for both methods was analysed by bicinchoninic acid and fluorescence assays, yielding efficiencies of 94?±?2% and 83?±?3% for the emulsion method and encapsulation device, respectively. Glucose oxidase from Aspergillus Niger and Laccase from Trametes Versicolor were encapsulated by both microencapsulation methods and their activities were compared.  相似文献   

17.
Purpose: To evaluate retinal nerve fiber layer thickness (RNFLT), ganglion cell layer thickness (GCLT), subfoveal choroidal thickness (SFCT), and central retinal thickness (CRT) in asthmatic children who were under inhaled corticosteroid treatment by using Swept-Source Optical Coherence Tomography (SS-OCT).

Material and methods: Fifty-three children were prospectively analyzed in the study. Group 1 included 31 asthmatic children and group 2 included 22 healthy children. Asthmatic children received a dose 250?μg daily of inhaled fluticasone propionate (Flexotide, GlaxoSmithKline, Middlesex, UK). Allergy parameters including, exposure to smoke, eosinophil count, percentage of eosinophils, immunoglobuline (Ig) E levels, number of asthma attacks, number of sensitivity to allergens and follow-up time were recorded. The RNFLT, GCLT, SFCT, and CRT were analyzed with SS-OCT and the data were compared between the groups.

Results: There were 13 girls (41.9%) and 18 boys (58.1%) in group 1 and 13 girls (59.1%) and 9 boys (40.9%) in group 2 (p?=?0.22). The mean age was 9.3?±?2.2 years in group 1 and 9.9?±?1.5 years in group 2 (p?=?0.08). The mean CRT (239.26?±?34.56 µm versus 226.82?±?26.23 µm, p?=?0.22) and mean SFCT (273.97?±?40.95 µm versus 280.41?±?32.78 µm, p?=?0.54) did not significantly differ between the groups. The superior, inferior, and average RNFLT were significantly lower in group 1 than group 2 (p?p?p?Conclusions: The SS-OCT revealed that asthmatic children under inhaled corticosteroid treatment have lower RNFLT than healthy subjects.  相似文献   

18.
《Journal of drug targeting》2013,21(10):821-830
Microparticles and nanoparticles used in drug delivery frequently depend on their movement in confined spaces such as cells. Liposomes containing small numbers of 1-µm diameter polystyrene particles were used to study the dynamics of their movement within the confined space of the liposome interior. The analysis of the trajectories of single and multiple entrapped particles revealed that the particles were largely localized toward the periphery of the liposome with a rare presence in the centre. Interparticle interactions were studied by calculating interparticle distances, ranging from close to zero to around 8 µm with a mean of ~4 µm. The diffusion coefficient of a single entrapped particle was D?=?0.27?×?10?9 cm2 s?1 when compared with 5.1?×?10?9 cm2 s?1 free in water. When more than one particle was entrapped, the calculated diffusion coefficients were D?=?0.61?×?10?9 cm2 s?1 for two particles, D?=?1.26?×?10?9 cm2 s?1 for three particles, and D?=?1.3?×?10?9 cm2 s?1 for multiple particles). Particle movement was found to be distinctly faster at the periphery (average velocity 21.4 μm s?1) than at the centre of the vesicle (average velocity 14.2 μm s?1). These results demonstrate the significance of particle–particle interactions as well as particle–surface interactions, which is evident here in some systems by particle aggregation close to the liposome membrane.  相似文献   

19.
The Bifidobacterium bifidum susceptibility in gastrointestinal conditions and storage stability limit its use as potential probiotics. The current study was design to encapsulate B. bifidum using sodium alginate (SA, 1.4% w/v) and different concentration of zein as coating material, that is, Z1 (1% w/v), Z2 (3% w/v), Z3 (5% w/v), Z4 (7% w/v), Z5 (9% w/v). The resultant microbeads were further investigated for encapsulation efficiency, survival in gastrointestinal conditions, release profile in intestinal fluid, storage stability and morphological characteristics. The highest encapsulation efficiency (94.56%) and viable count (>107 log CFU/g) was observed in Z4 (7% w/v). Viable cell count of B. bifidum was >106 log CFU/g in all the zein-coated microbeads as compare to free cells (103 log CFU/g) and SA (105 log CFU/g) at 4 °C after 32 days of storage. Therefore, B. bifidum encapsulated in zein-coated alginate microbeads present improved survival during gastric transit and storage.  相似文献   

20.
The aim of this study was to optimize the production of BSA-loaded alginate microcapsules by spray drying and to study the release of bovine serum albumin fraction V (BSA) under gastric simulated conditions. Microcapsule yield, BSA release, microcapsule size and size distribution were characterized following the application of different production parameters including inlet air temperature, inlet air pressure and liquid feed rate. The microcapsules were incubated in 0.1?N HCl and BSA release was quantified over time. The yields were higher with the pressure of 3?bar compared to 4?bar and with a feed rate of 0.45 vs. 0.2?ml?s?1. A high feed rate (0.45 vs. 0.2?ml?s?1) allows one to obtain microcapsules with a low BSA release (p?=?0.0327). The increase of the atomizer inlet temperature leads to microcapsules with a higher BSA release (p?=?0.0230). A higher air pressure of 4?bar compared to 3?bar resulted in a lower microcapsule size (2.55 vs. 2.80?µm) and led to a narrower size distribution (0.92 vs. 1.07). In conclusion, the spray dryer parameters influenced the alginate microcapsule characteristics as well as subsequent protein release into a simulated gastric medium.  相似文献   

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