共查询到20条相似文献,搜索用时 15 毫秒
1.
XiaoQing Dong Jun Xu WeiCai Wang Hao Luo XiaoFei Liang Lei Zhang HanJie Wang PengHua Wang Jin Chang 《中国科学C辑(英文版)》2008,51(11):1039-1044
In this study the w/o/w extraction-evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The microspheres were characterized
for morphology by transmission electron microscopy (TEM) and particle size distribution. The release performances, the proliferation
effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied. The results showed that these spherical
microspheres had a narrow size distribution and a high drug encapsulation efficiency (85.6%). RhEGF-loaded microspheres enhanced
the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF. The number of the proliferating cell nuclear
antigen (PCNA) in the epidermis layer with the microsphere treatment was significantly larger than those of the control groups.
Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy
for diabetic ulcer repair. 相似文献
2.
The system poly(lactic-co-glycolic) acid/ piroxicam (PLGA/PX) was selected, as a model system, to evaluate the effectiveness of supercritical carbon dioxide (SC-CO(2)) extraction of the oily phase (ethyl acetate) from oil-in-water emulsions used in the production of polymer/drug microspheres for sustained drug release applications. The influence of process parameters like operating pressure and temperature, flow rate and contacting time between the emulsion and SC-CO(2) was studied with respect to the microsphere size, distribution and solvent residue. Different polymer concentrations in the oily phase were also tested in emulsions formulation to monitor their effects on droplets and microspheres size distribution at fixed mixing conditions. Spherical PLGA microspheres loaded with PX (10% w/w) with mean sizes ranging between 1 and 3 microm and very narrow size distributions were obtained due to the short supercritical processing time (30 min) that prevents the aggregation phenomena typically occurring during conventional solvent evaporation process. A solvent residue smaller than 40 ppm was also obtained at optimized operating conditions. DSC and SEM-EDX analyses confirmed that the produced microparticles are formed by a solid solution of PLGA and PX and that the drug is entrapped in an amorphous state into the polymeric matrix with an encapsulation efficiency in the range of 90-95%. Drug release rate studies showed very uniform drug concentration profiles, without any burst effect, confirming a good dispersion of the drug into the polymer particles. 相似文献
3.
DONG XiaoQing XU Jun WANG WeiCai Luo Hao LIANG XiaoFei Zhang Lei Wang HanJie Wang PengHua & CHANG Jin 《中国科学:生命科学英文版》2008,51(11):1039-1044
In this study the w/o/w extraction–evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The micro-spheres were characterized for morphology by transmission electron microscopy (TEM) and particle size distribution. The release performances, the proliferation effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied. The results showed that these spherical micro-spheres had a narrow size distribution and a high drug encapsulation efficiency (85.6%). RhEGF-loaded microspheres enhanced the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF. The number of the proliferating cell nuclear antigen (PCNA) in the epidermis layer with the mi-crosphere treatment was significantly larger than those of the control groups. Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy for diabetic ulcer repair. 相似文献
4.
Formation and oral administration of alginate microspheres loaded with pDNA coding for lymphocystis disease virus (LCDV) to Japanese flounder 总被引:1,自引:0,他引:1
Oral delivery of plasmid DNA (pDNA) is a desirable approach for fish immunization in intensive culture. However, its effectiveness is limited because of possible degradation of pDNA in the fish's digestive system. In this report, alginate microspheres loaded with pDNA coding for fish lymphocystis disease virus (LCDV) and green fluorescent protein were prepared with a modified oil containing water (W/O) emulsification method. Yield, loading percent and encapsulation efficiency of alginate microspheres were 90.5%, 1.8% and 92.7%, respectively. The alginate microspheres had diameters of less than 10 microm, and their shape was spherical. As compared to sodium alginate, a remarkable increase of DNA-phosphodiester and DNA-phosphomonoester bonds was observed for alginate microspheres loaded with pDNA by Fourier transform infrared (FTIR) spectroscopic analysis. Agarose gel electrophoresis showed a little supercoiled pDNA was transformed to open circular and linear pDNA during encapsulation. The cumulative release of pDNA in alginate microspheres was or=0.3) for anti-LCDV antibody from week 3 to week 16 for fish orally vaccinated with alginate microspheres loaded with pDNA, in comparison with fish orally vaccinated with naked pDNA. Our results display that alginate microspheres obtained by W/O emulsification are promising carriers for oral delivery of pDNA. This encapsulation technique has the potential for DNA vaccine delivery applications due to its ease of operation, low cost and significant immune effect. 相似文献
5.
Chemical sensors utilizing immobilized enzymes and proteins are important for monitoring chemical processes and biological systems. In this study, calcium-cross-linked alginate hydrogel microspheres were fabricated as enzyme carriers by an emulsification technique. Glucose oxidase (GOx) was encapsulated in alginate microspheres using three different methods: physical entrapment (emulsion), chemical conjugation (conjugation), and a combination of physical entrapment and chemical conjugation (emulsion-conjugation). Nano-organized coatings were applied on alginate/GOx microspheres using the layer-by-layer self-assembly technique in order to stabilize the hydrogel/enzyme system under biological environment. The encapsulation of GOx and formation of nanofilm coating on alginate microspheres were verified with FTIR spectral analysis, zeta-potential analysis, and confocal laser scanning microscopy. To compare both the immobilization properties of enzyme encapsulation techniques and the influence of nanofilms with uncoated microspheres, the relationship between enzyme loading, release, and effective GOx activity (enzyme activity per unit protein loading) were studied over a period of four weeks. The results produced four key findings: (1) the emulsion-conjugation technique improved the stability of GOx in alginate microspheres compared to the emulsion technique, reducing the GOx leaching from microsphere from 50% to 17%; (2) the polyelectrolyte nanofilm coatings increased the GOx stability over time, but also reduced the effective GOx activity; (3) the effective GOx activity for the emulsion-conjugation technique (about 3.5 x 10(-)(5) AU microg(-)(1) s(-)(1)) was higher than that for other methods, and did not change significantly over four weeks; and (4) the GOx concentration, when compared after one week for microspheres with three bilayers of poly(allylamine hydrochloride)/sodium poly(styrene sulfonate) ({PAH/PSS}) coating, was highest for the emulsion-conjugation technique. As a result, the comparison of these three techniques showed the emulsion-conjugation technique to be a potentially effective and practical way to fabricate alginate/GOx microspheres for implantable glucose biosensor application. 相似文献
6.
7.
Encapsulation of protein nanoparticles into uniform-sized microspheres formed in a spinning oil film
Leach WT Simpson DT Val TN Yu Z Lim KT Park EJ Williams RO Johnston KP 《AAPS PharmSciTech》2005,6(4):E605-E617
A new spinning oil film (SOF) solid-in-oil-in-oil emulsion process was developed to produce uniform-sized proteinloaded biodegradable
microspheres. A thin SOF on a cylindrical rotor was used to shear droplets from a nozzle tip to control droplet size. The
resulting microspheres with low polydispersity (6%) produced a low burst (6%–11%) release even at high loadings (13%–18% encapsulated
solids, 8%–12% protein). The SOF process had a high yield and did not require the presence of water, which can cause protein
denaturation, or surfactants, which may be unwanted in the final product. Amorphous protein and crystalline excipient solids
were encapsulated into 3 different polymers, giving a homogenous drug distribution throughout the microspheres, and an essentially
complete protein encapsulation efficiency (average=99%). In contrast, large burst release was observed for polydisperse microspheres
produced by a conventional emulsification technique, particularly for microspheres smaller than 25 μm in diameter, which gave
93% burst at 15% loading. The uniform encapsulation of high loadings of proteins into microspheres with low polydispersity
in an anhydrous process is of practical interest in the development of controlled-release protein therapeutics.
Published: December 6, 2005 相似文献
8.
目的:以牛血清白蛋白(BSA)作为模型药物,制备壳聚糖/有机累托石复合物微球,建立一种安全有效的药物控释传递系统。方法:壳聚糖(CS)/有机累托石(OREC)和海藻酸钠,按照不同的混合比例交联,在Ca2+水溶液中包裹BSA而形成壳核结构的微球。采用傅立叶红外光谱(FTIR)、动态光散射(DLS)、原子力显微镜(AFM)、X-衍射(XRD)、扫描电镜(SEM)和透射电镜(TEM)观察研究微球的形态、CS和OREC的插层结构、BSA的包封率和控释效果。结果:口光学显微镜和扫描电镜观察显示,形成了壳核结构的微球。傅里叶变换光谱和X-射线能量分散显示,OREC存在于微球中。小角X-射线衍射证实,CS链成功的插入OREC插层中。BSA的包封率和控释检测结果显示,与纯的CS/ALG形成的微球相比较,CO复合物所形成的微球药物释放率明显提高。结论:OREC-HTCC纳米粒子是良好的蛋白药物载体,具有包封率高、缓释效果好等优点,为CS-OREC作为潜在的药物给药系统的进一步应用提供科学依据。 相似文献
9.
In this study, ethylcellulose (EC)-based microsphere formulations were prepared without and with triethyl citrate (TEC) content
of 10% and 30% by water-in-oil emulsion-solvent evaporation technique. Diltiazem hydrochloride (DH) was chosen as a hydrophilic
model drug and used at different drug/polymer ratios in the microspheres. The aim of the work was to evaluate the influence
of plasticizer ratio on the drug release rate and physicochemical characteristics of EC-based matrix-type microspheres. The
resulting microspheres were evaluated for encapsulation efficiency, particle size and size distribution, surface morphology,
total pore volume, thermal characteristics, drug release rates, and release mechanism. Results indicated that the physicochemical
properties of microspheres were strongly affected by the drug/polymer ratio investigated and the concentration of TEC used
in the production technique. The surface morphology and pore volume of microspheres significantly varied based on the plasticizer
content in the formulation. DH release rate from EC-based matrix-type microspheres can be controlled by varying the DH to
polymer and plasticizer ratios. Glass transition temperature values tended to decrease in conjunction with increasing amounts
of TEC. Consequently, the various characteristics of the EC microspheres could be modified based on the plasticized ratio
of TEC. 相似文献
10.
Characterization of an encapsulation device for the production of monodisperse alginate beads for cell immobilization 总被引:6,自引:0,他引:6
Serp D Cantana E Heinzen C Von Stockar U Marison IW 《Biotechnology and bioengineering》2000,70(1):41-53
An encapsulation device, designed on the basis of the laminar jet break-up technique, is characterized for cell immobilization with different types of alginate. The principle of operation of the completely sterilizable encapsulator, together with techniques for the continuous production of beads from 250 microm to 1 mm in diameter, with a size distribution below 5%, at a flow rate of 1-15 mL/min, is described. A modification of the device, to incorporate an electrostatic potential between the alginate droplets and an internal electrode, results in enhanced monodispersity with no adverse effects on cell viability. The maximum cell loading capacity of the beads strongly depends on the nozzle diameter as well as the cells used. For the yeast Phaffia rhodozyma, it is possible to generate 700 microm alginate beads with an initial cell concentration of 1 x 10(8) cells/mL of alginate whereas only 1 x 10(6) cells/ml could be entrapped within 400 microm beads. The alginate beads have been characterized with respect to mechanical resistance and size distribution immediately after production and as a function of storage conditions. The beads remain stable in the presence of acetic acid, hydrochloric acid, water, basic water, and sodium ions. The latter stability applies when the ratio of sodium: calcium ions is less than 1/5. Complexing agents such as sodium citrate result in the rapid solubilization of the beads due to calcium removal. The presence of cells does not affect the mechanical resistance of the beads. Finally, the mechanical resistance of alginate beads can be doubled by treatment with 5-10 kDa chitosan, resulting in reduced leaching of cells. 相似文献
11.
Novel attrition-resistant and spherical enzyme granules encapsulating active subtilisin were formed by emulsification of 2% alginate sol loaded with active enzyme, instantaneous gelation triggered through in situ release of Ca(2+) (internal gelation), particle separation, and finally acetone extractive drying. Granular subtilisin was highly active, readily dispersible, and mechanically robust. This technique serves as a new and attractive alternative to established enzyme granulation processes, such as fluid bed coating, extrusion followed by marumerization, drum granulation, or prilling, for use in industrial enzyme applications such as detergents, textile manufacturing, and food processing. The formulation and encapsulation conditions were optimized to maximize the resistance of the granule to compression and impact forces, consistent with enzyme release and particle dispersion in detergent solutions. Well characterized alginates, with specified guluronic/mannuronic acid (G/M) content and molecular weight, were used in the formulation. The characteristics of the resulting microspheres, including their size and distribution, morphology, shrinkage, compression resistance, impact strength, solubility and encapsulation yield, were examined. Spherical dry granules were formulated with a mean diameter of 500 microm with particle sizes ranging from 300 to 800 microm. Dry alginate granules were discrete, spherical, and glossy white and exhibited impact strength, compression resistance, and solubility difference dependent on composition. Reduced starch levels, high alginate concentration, low alginate molecular weight, and use of high guluronate alginates resulted in the lowest dust level and highest compression resistance. Subtilisin mass yields were approximately 50%, and specific activity yields ranged from 60% to 100%. A formulation consisting of 3% SG150 alginate, 10% starch, 10% TiO(2), and 1% CaCO(3) provided granules appropriate for use in detergent application. 相似文献
12.
DNA encapsulation by an air-agitated, liquid-liquid mixer 总被引:1,自引:0,他引:1
Smooth and spherical alginate microspheres and nylon-membrane bound microcapsules were formed in an air-agitated, liquid-liquid mixer by emulsification/internal gelation and interfacial polymerization respectively. The mean diameter of the alginate microspheres ranged from 100 to 800 mum, and was controlled by process modifications. Increase in emulsifier concentration, gas flowrate, and emulsification time resulted in smaller microsphere size as did a decrease in liquid height. Increase in the dispersed phase viscosity resulted in a longer emulsification time required for approaching a minimum microsphere size. Microspheres could be formed with the proportion of dispersed phase approaching 30%. The yield of alginate microspheres was 70%, with losses attributed to incomplete recovery during washing and filtration operations. The yield of DNA encapsulation within the fraction of recovered microspheres, was 94%. The small loss was thought to occur by surface release during the washing of the microspheres. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 464-470, 1997. 相似文献
13.
Microencapsulation within hydrogel microspheres holds much promise for drug and cell delivery applications. Synthetic hydrogels have many advantages over more commonly used natural materials such as alginate, however their use has been limited due to a lack of appropriate methods for manufacturing these microspheres under conditions compatible with sensitive proteins or cells. This study investigated the effect of flow rate and voltage on size and uniformity of the hydrogel microspheres produced via submerged electrospray combined with UV photopolymerization. In addition, the mechanical properties and cell survival within microspheres was studied. A poly(vinyl alcohol) (PVA) macromer solution was sprayed in sunflower oil under flow rates between 1-100 μL/min and voltages 0-10 kV. The modes of spraying observed were similar to those previously reported for electrospraying in air. Spheres produced were smaller for lower flow rates and higher voltages and mean size could be tailored from 50 to 1,500 μm. The microspheres exhibited a smooth, spherical morphology, did not aggregate and the compressive modulus of the spheres (350 kPa) was equivalent to bulk PVA (312 kPa). Finally, L929 fibroblasts were encapsulated within PVA microspheres and showed viability >90% after 24 h. This process shows great promise for the production of synthetic hydrogel microspheres, and specifically supports encapsulation of cells. 相似文献
14.
15.
Enrique Galindo Carlos Peña Cinthia Núñez Daniel Segura Guadalupe Espín 《Microbial cell factories》2007,6(1):7
Several aspects of alginate and PHB synthesis in Azotobacter vinelandii at a molecular level have been elucidated in articles published during the last ten years. It is now clear that alginate
and PHB synthesis are under a very complex genetic control. Genetic modification of A. vinelandii has produced a number of very interesting mutants which have particular traits for alginate production. One of these mutants
has been shown to produce the alginate with the highest mean molecular mass so far reported. Recent work has also shed light
on the factors determining molecular mass distribution; the most important of these being identified as; dissolved oxygen
tension and specific growth rate. The use of specific mutants has been very useful for the correct analysis and interpretation
of the factors affecting polymerization. Recent scale-up/down work on alginate production has shown that oxygen limitation
is crucial for producing alginate of high molecular mass, a condition which is optimized in shake flasks and which can now
be reproduced in stirred fermenters. It is clear that the phenotypes of mutants grown on plates are not necessarily reproducible
when the strains are tested in lab or bench scale fermenters. In the case of PHB, A. vinelandii has shown itself able to produce relatively large amounts of this polymer of high molecular weight on cheap substrates, even
allowing for simple extraction processes. The development of fermentation strategies has also shown promising results in terms
of improving productivity. The understanding of the regulatory mechanisms involved in the control of PHB synthesis, and of
its metabolic relationships, has increased considerably, making way for new potential strategies for the further improvement
of PHB production. Overall, the use of a multidisciplinary approach, integrating molecular and bioengineering aspects is a
necessity for optimizing alginate and PHB production in A. vinelandii. 相似文献
16.
Mohsen Tafaghodi Maryam Eskandari Ali Khamesipour Mahmoud R. Jaafari 《Experimental parasitology》2011,129(2):107-114
A suitable adjuvant and delivery system are needed to enhance efficacy of vaccines against leishmaniasis. In this study, alginate microspheres as an antigen delivery system and CpG-ODN as an immunoadjuvant were used to enhance immune response and induce protection against an experimental autoclaved Leishmania major (ALM) vaccine. Alginate microspheres were prepared by an emulsification technique and the characteristics of the preparation such as size, encapsulation efficiency and release profile of encapsulates were studied. Mean diameter of microspheres was determined using SEM (Scanning Electron Microscopy) and particle size analyzer. The encapsulation efficiency was determined using Lowry protein assay method. The integrity of ALM antigens was assessed using SDS–PAGE. Mean diameter of microspheres was 1.8 ± 1.0 μm. BALB/c mice were immunized three times in 3-weeks intervals with ALM + CpG-ODN loaded microspheres [(ALM + CpG)ALG], ALM encapsulated alginate microspheres [(ALM)ALG], (ALM)ALG + CpG, ALM + CpG, ALM alone or PBS. The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection was observed in group of mice immunized with (ALM + CpG)ALG. The groups of mice received (ALM + CpG)ALG, (ALM)ALG + CpG, (ALM)ALG and ALM + CpG were also showed a significantly (P < 0.05) smaller footpad swelling compared with the group that received either ALM alone or PBS. The mice immunized with (ALM + CpG)ALG or ALM + CpG showed the significantly (P < 0.05) highest IgG2a/IgG1 ratio. The IFN-γ level was significantly (P < 0.0001) highest in group of mice immunized with either (ALM)ALG + CpG or ALM + CpG. It is concluded that alginate microspheres and CpG-ODN adjuvant when are used simultaneously induced protection and enhanced immune response against ALM antigen. 相似文献
17.
In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique
is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose,
poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures
above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during
preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied.
As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing
the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 μm to 104 μm. The drug release
rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low
drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres
from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from
matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release
was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted
in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles
of naltrexone can be achieved using a PLA microparticulate system or matrix devices. 相似文献
18.
尺寸均一的壳聚糖微球的制备及其作为胰岛素控释载体的研究 总被引:3,自引:1,他引:2
采用新型微孔膜乳化技术制备了载胰岛素的壳聚糖微球。研究表明,要制备粒径均一的壳聚糖微球,必须将亲水性膜修饰成疏水性;制得的微球粒径和所采用的膜孔径之间存在很好的线性关系,使得微球粒径可控;以胰岛素为模型药物,主要考察了交联剂用量和交联时间对微球表面形态、药物包埋率和微球体外释药特性的影响。结果表明当氨基与醛基的摩尔比为1∶0.7、交联时间为1h时,所得载药微球的包埋率最高,随着戊二醛用量的增加和交联时间的延长,药物体外释放速率减慢。 相似文献
19.
Oleksandr Gryshkov Denys Pogozhykh Nicola Hofmann Olena Pogozhykh Thomas Mueller Birgit Glasmacher 《PloS one》2014,9(9)
Alginate cell-based therapy requires further development focused on clinical application. To assess engraftment, risk of mutations and therapeutic benefit studies should be performed in an appropriate non-human primate model, such as the common marmoset (Callithrix jacchus). In this work we encapsulated amnion derived multipotent stromal cells (MSCs) from Callithrix jacchus in defined size alginate beads using a high voltage technique. Our results indicate that i) alginate-cell mixing procedure and cell concentration do not affect the diameter of alginate beads, ii) encapsulation of high cell numbers (up to 10×106 cells/ml) can be performed in alginate beads utilizing high voltage and iii) high voltage (15–30 kV) does not alter the viability, proliferation and differentiation capacity of MSCs post-encapsulation compared with alginate encapsulated cells produced by the traditional air-flow method. The consistent results were obtained over the period of 7 days of encapsulated MSCs culture and after cryopreservation utilizing a slow cooling procedure (1 K/min). The results of this work show that high voltage encapsulation can further be maximized to develop cell-based therapies with alginate beads in a non-human primate model towards human application. 相似文献
20.
Christina M.E. Bitar Karen E. Markwick Dušana Treľová Zuzana Kroneková Michal Pelach Chloé M.O. Selerier James Dietrich Igor Lacík Corinne A. Hoesli 《Biotechnology progress》2019,35(6):e2851
In this study, we developed a high-throughput microchannel emulsification process to encapsulate pancreatic beta cells in monodisperse alginate beads. The process builds on a stirred emulsification and internal gelation method previously adapted to pancreatic cell encapsulation. Alginate bead production was achieved by flowing a 0.5–2.5% alginate solution with cells and CaCO3 across a 1-mm thick polytetrafluoroethylene plate with 700 × 200 μm rectangular straight-through channels. Alginate beads ranging from 1.5–3 mm in diameter were obtained at production rates exceeding 140 mL/hr per microchannel. Compared to the stirred emulsification process, the microchannel emulsification beads had a narrower size distribution and demonstrated enhanced compressive burst strength. Both microchannel and stirred emulsification beads exhibited homogeneous profiles of 0.7% alginate concentration using an initial alginate solution concentration of 1.5%. Encapsulated beta cell viability of 89 ± 2% based on live/dead staining was achieved by minimizing the bead residence time in the acidified organic phase fluid. Microchannel emulsification is a promising method for clinical-scale pancreatic beta cell encapsulation as well as other applications in the pharmaceutical, food, and cosmetic industries. 相似文献