用多孔明胶微球作为示踪剂载体

用天然胶原蛋白加交联剂制备多孔明腔微球，直径３０－６０μｍ，含微孔。将其作为荧光金载体用于垂体前叶神经纤维原的研究获得较理想的结果，并有以下优点：１．吸收示踪剂硬结后可按需要捣成直径６０μｍ以上坚硬颗粒，使用方便，２．供示踪会着的表面积大，运载示踪剂量多；３．示踪剂从微球中缓慢释放；４．明胶化学性质稳定，不影响示踪剂活性或神经组织吸收摄取示踪剂的能力。     

功能高分子微球研究：99MTC明胶微球的制备及其动物活体显像

以聚合物溶液为分散介质、戊二醛为交联剂可制备出具有高反应活性的明胶微球(GM)。通过改变聚合物溶液浓度、调节反应搅拌速度可控制微球粒径。当聚合物溶液浓度为25％、搅拌速度为250rpm时,可得到10～50um粒径范围的明胶微球。用此法制备的明胶微球表面光滑、亲水性好、贮存期长、~(99m)Tc标记率高,经静脉注射后,能定向进入肺部。初步实验表明,明胶微球可望作为肺灌注显像剂;成为质优、价廉、使用方便的肺部疾患诊断用新材料。     

壳聚糖微球体外降脂活性研究

目的为使壳聚糖能更好地用于减肥降脂,必须提高壳聚糖的降脂活性和降低其毒副作用。方法用喷雾干燥法制备壳聚糖微球,在体外模拟人体消化系统环境考察壳聚糖微球对脂类的结合能力。结果壳聚糖微球粒径范围在2—5μm且用量90mg时对脂类的结合能力达19．53gig,对胆酸的结合能力达27．35mg／g,用量120mg时对游离脂肪酸的结合能力达18．25mg／g,均显著高于普通壳聚糖。结论壳聚糖微球是提高壳聚糖降脂活性的一种有效途径,该研究为新一代壳聚糖减肥类产品的后续开发提供了理论依据。     

明胶微球乙肝疫苗动物免疫效果研究

目的 研究并优化微球乙型肝炎疫苗的配方,观察微球乙肝疫苗对温度的稳定性。方法 用明胶包裹ＨＢｓ制备微球,设计不同配方及不同粒径微球乙肝疫苗、冻干微球乙肝疫苗于不同温度放置一定时间,免疫动物观察免疫效果。结果 微球疫苗ＨＢｓ包裹率〉９０％,微球疫苗的免疫效果受佐剂配方及制备程序等因素影响,〈１０μｍ的微球（５．６μｍ）免疫效果明显优于〉１０μｍ的微球（２５．４μｍ）（Ｐ〈０．０２）及铝佐剂组（Ｐ〈０     

平阳霉素明胶微球的制备及其释药特性

采用优化的双相乳化冷凝聚合法，制备粒径适当的平阳霉素明胶微球，研究其体内外和颈动脉栓塞化疗的释药特性；并对介入栓塞给药、静脉给药、灌注给药3种方法的效果加以对比分析。结果表明明胶微球粒径分布较好，体外释药有明显的缓释作用，微球颈动脉栓塞可以显著提高肿瘤化疗效果。     

壳聚糖微球药物释放机制研究进展

近年来已有多种药物实现了以壳聚糖微球作为缓控释载体,并在生物医学领域展现出良好的应用前景,成为缓控释剂型研究的热点之一。目前对壳聚糖微球释放机制的研究进展落后于壳聚糖载药微球制备与应用的研究进展,而加强壳聚糖载药微球药物释放机制的研究,有利于更好地了解药物的释放行为和释放影响因素,并对深入研究壳聚糖缓释载药体系的制备与应用具有重要意义。主要从壳聚糖微球的药物释放机制、药物释放行为描述、药物释放影响因素等方面进行了综述。     

制备复合生长因子的缓释微球并考察其对细胞的影响

目的:制备复合碱性成纤维细胞生长因子的可降解缓释微球,考察其生物活性保存情况,以及其对上皮细胞的作用.方法:采用改良的乳化冷凝法交联制备明胶缓释微球,将其加入上皮细胞的培养液中,用细胞计数法、四甲基偶氮唑盐微量反应比色法(MTT法)测定细胞增殖情况.结果:缓释微球平均粒径(12.36±3.56)μm;培养1 d后各组细胞计数、吸光度(A)值差异均无显著性意义;5 d后,缓释微球组细胞计数、吸光度(A)值明显高于对照组;7 d后,缓释微球组值仍高于其它组,但差异无显著性意义.结论:复合生长因子的缓释微球制备工艺简便,成球性好;能较长时间持续释放活性生长因子,明显促进细胞增殖.     

壳聚糖胰岛素微球在糖尿病大鼠中的降糖作用研究

我们观察了壳聚糖为载体的胰岛素微球的口服制剂对链脲菌素致糖尿病大鼠的降血糖作用.用扫描电镜观察正常大鼠管饲壳聚糖胰岛素微球后1、2、3、7d微球在大鼠体内的分布.18只链脲佐菌素致糖尿病大鼠被随机分成3组壳聚糖胰岛素微球管饲组(120U/kg,n=6);诺和灵中效胰岛素皮下注射组(24U/kg,n=6),空白对照组(管饲等容积的蒸馏水,n=6).另有5只正常大鼠作为正常对照组(管饲等容积的蒸馏水,n=5).分别测定4组大鼠用药前后的血糖值,并做组间分析比较.结果表明(1)壳聚糖胰岛素微球能通过大鼠的小肠吸收,并靶向分布于小肠、肝、脾等器官.(2)壳聚糖胰岛素微球管饲组在管饲微球后第1天,糖尿病大鼠的血糖从24.7±3.2mmol/L下降至16.9±5.5mmol/L,第2天降至最低12.1±5.7mmol/L,第3天开始逐渐回升至用药前水平,血糖最大下降幅度为50.2%.诺和灵中效胰岛素皮下注射组注射胰岛素后,糖尿病大鼠的血糖从25.2±3.8mmol/L下降至10.4±5.2mmol/L,第2天开始逐渐回升至用药前水平,血糖最大下降幅度为58.7%.两组下降幅度比较无统计学差异(P＞0.05).而空白对照组和正常对照组大鼠的血糖无明显变化,但它们分别和前两组比较,具有统计学差异(P＜0.001).因此,我们认为对链脲菌素致糖尿病大鼠,管饲壳聚糖胰岛素微球具有一定程度的降糖效果.     

明胶-海藻酸盐复合微球与凝胶修复软骨损伤

背景:软骨损伤的微创治疗对于微载体的要求较高,需要其有较高的细胞相容性、较强的细胞黏附力、较好的力学性能与低免疫原性。同时,临床使用条件相比实验室更加苛刻,在微创或注射使用微载体时液态微载体要明显优于固态微载体。目的:制备一种全新的高分子有机微载体,以用于修复软骨缺损。方法:通过明胶与液体石蜡(W/O)混合搅拌的化学乳化法制备浓度为6%的明胶微球,冻干后用无水乙醇处理固定,再使用紫外交联法固定,电镜观察微球形态。配置浓度为7%的海藻酸钠凝胶,与明胶微球混合孵育2 h,制备明胶-海藻酸盐复合凝胶。将脂肪间充质干细胞悬液滴入明胶-海藻酸盐复合凝胶中孵育24 h,滴入5%CaCl2溶液中充分交联,制备含细胞明胶-海藻酸盐复合微球。采用CCK-8法检测无细胞明胶-海藻酸盐复合微球浸提液的细胞毒性;利用死活染色观察含细胞明胶-海藻酸盐复合微球的细胞活性;将约1 mL明胶-海藻酸盐复合凝胶吸入10 mL针管进行注射,对未注射与注射1,3次的凝胶进行光镜观察。结果与结论:(1)扫描电镜下可见,明胶微球孔隙相对均一且表面有层次感,微球粒径大多分布在180-500μm之间;(2)死活染色显示,培养24 ...     

明胶-聚乳酸载药纳米微球的制备及其体外释药研究

采用复合乳液—溶剂挥发法制得明胶—聚乳酸载五氟脲嘧啶(5—Fu)微球，以混合型乳化剂Tween—80：Span—80＝5：1—作为初乳乳化剂，O—羧甲基壳聚糖作为复乳乳化剂，考察了明胶—聚乳酸载药微球的制备条件对微球的成球性、药物包封率及体外释药的影响。结果表明乳化剂的选择、内部水相药物浓度和PLA分子量等均对载药微球的结构与性能产生影响，经优化条件得到了成球性和体外释放都比较好的载药微球。     

Optimization of spray drying by factorial design for production of hollow microspheres for ultrasound imaging

A process for producing hollow microcapsules as ultrasound contrast agents was optimized using a 2(3) factorial experimental design method with two replicates. Spray drying, a conveniently scalable encapsulation technique, was used to encapsulate a volatile core material, such as ammonium carbonate, using biodegradable 50-50 poly(D,L-lactide-co-glycolide). Various effects due to changes in processing variables and their interactions were studied using the factorial grid. The high- and low-incremented variables examined included the temperature difference between the inlet and outlet of the spray dryer (5 degrees and 15 degrees C), air atomization pressure (80 and 100 psi), and polymer concentration in solvent (0.005 and 0.025 g/mL). Responses analyzed for computing the main effects and interactions were microcapsule morphology, yield, mean size, and zeta potential. Experimental results showed that polymer concentration was most important for determining microcapsule morphology. The temperature difference for drying prominently affected mean size, and atomization pressure was the main effect for microcapsule yield. Interactions among variables were not present in this case. The best conditions for producing PLGA microcapsules was a temperature difference of 5 degrees C, an initial polymer concentration of 0.005 g/mL, and an atomization pressure of 80 psi. The microcapsule zeta potentials were unaffected by spray-drying conditions.     

In vitro evaluation of the effectiveness and cytotoxicity of meglumine antimoniate microspheres produced by spray drying against Leishmania infantum

The aim of the present study was to evaluate the in vitro activity and cytotoxicity of meglumine antimoniate microspheres produced by spray drying on Leishmania infantum and the effect of the excipients used in them. The parasite strain shows sensitivity to the meglumine antimoniate microspheres prepared. All the antimony IC₅₀ values from encapsulated meglumine antimoniate (3.80 ± 0.34 to 9.53 ± 0.70 μg SbV/ml for promastigotes assay) are considerably lower compared to the mean value of IC₅₀ in Glucantime solution (112 ± 12.74 μg SbV/ml). Interesting IC₅₀ values for the excipient chitosan (112.64 ± 0.53 mg/ml for promastigotes and 100.81 ± 26.45 mg/ml for amastigotes) were obtained (without cytotoxic activity), whereas the rest of the excipients did not show any activity. This new delivery system could offer a new pharmacological tool for the treatment of leishmaniosis that reduces the doses required, lowering toxic side effects because of meglumine antimoniate.     

A new approach to prepare well-dispersed CaF(2) nanoparticles by spray drying technique

Previously, nano-sized calcium fluoride (CaF?) particles were prepared using a spray drying method by simultaneously feeding Ca(OH)? and NH?F solutions to a two-liquid nozzle. The aim of the present study was to prepare better-dispersed nano-CaF? particles by co-forming a soluble salt, sodium chloride (NaCl). NaCl of various concentrations were added to the NH(4) F solution, leading to formation of (CaF? +NaCl) composites with CaF? /NaCl molar ratios of 4/1, 4/4, and 4/16. Pure nano-CaF? was also prepared as the control. Powder X-ray diffraction analysis showed that the products contained crystalline CaF? and NaCl. Scanning electron microscopy examinations showed that both the CaF? /NaCl composite and pure CaF? particles were about (50-800) nm in size and consisted of primary CaF? particles of < 50 nm in size. BET surface area measurements showed similar primary particle sizes for all samples. Dynamic light scattering measurements showed that the washed (CaF?+NaCl) particles were much smaller than the pure CaF? as the dissolution of NaCl "freed" most of the primary CaF? particles, leading to a greater degree of particle dispersion. The well-dispersed nano-CaF? may be expected to be a more effective anticaries agent than NaF by providing longer lasting elevations of fluoride concentrations in oral fluids.     

Preparation, characterization, and in vitro evaluation of physostigmine-loaded poly(ortho ester) and poly(ortho ester)/poly(D,L-lactide-co-glycolide) blend microspheres fabricated by spray drying

The physostigmine-loaded poly(ortho ester) (POE), poly(dl-lactide-co-glycolide) (PLGA) and POE/PLGA blend microspheres were fabricated by a spray drying technique. The in vitro degradation of, and physostigmine release from, the microspheres were investigated. SEM analysis showed that the POE and POE/PLGA blend particles were spherical. They were better dispersed when compared to the pure PLGA microspheres. Two glass transition temperature ( Tg ) values of the POE/PLGA blend microspheres were observed due to the phase separation of POE and PLGA in the blend system. XPS analysis proved that POE dominated the surfaces of POE/PLGA blend microspheres, indicating that the blend microspheres were coated with POE. The encapsulation efficiencies of all the microspheres were more than 95%. The incorporation of physostigmine reduced the Tg value of microspheres. The Tg value of the degrading microspheres increased with the release of physostigmine. For instance, POE blank microspheres and physostigmine-loaded POE microspheres had a Tg value of 67 degrees C and 48 degrees C, respectively. After 19 days in vitro incubation, Tg of the degrading POE microspheres increased to 55 degrees C. Weight loss studies showed that the degradation of the blend microspheres was accelerated with the presence of PLGA because its degradation products catalyzed the degradation of both POE and PLGA. The release rate of physostigmine increased with increase of PLGA content in the blend microspheres. The initial burst release of physostigmine was effectively suppressed by introducing POE to the blend microspheres. However, there was an optimized weight ratio of POE to PLGA (85:15 in weight), below which a high initial burst was induced. The POE/PLGA blend microspheres may make a good drug delivery system.     

Preparation of chitosan-gelatin hybrid scaffolds with well-organized microstructures for hepatic tissue engineering

The structural organization of natural liver is instrumental in the multifunctionality of hepatocytes, and mimicking these specific architectures in tissue-engineered scaffold plays an important role in the engineering of an implantable liver equivalent in vitro. To achieve this goal, we have developed a novel fabrication process to create chitosan-gelatin hybrid scaffolds with well-organized architectures and highly porous structures by combining rapid prototyping, microreplication and freeze-drying techniques. The scaffolds obtained not only have analogous configurations of portal vein, central vein, flow-channel network and hepatic chambers, but also have high (>90%) porosity, with the mean pore size of 100microm. Swelling and degradation studies showed that the scaffold has excellent properties of hydrophilicity and biodegradability. A hepatocyte culture experiment was conducted to evaluate the efficiency of the well-defined chitosan-gelatin scaffold in facilitating hepatocyte growth in the inner layer of the scaffold in vitro. Scanning electron microscopy and histological analysis showed that hepatocytes could form large colonies in the predefined hepatic chambers, and these cavities could the completely filled with hepatocytes during 7 day culture. Albumin secretion and urea synthesis further indicated that the well-organized scaffolds were more suitable for hepatocyte culture.     

Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds

A novel biodegradable hydroxyapatite/chitosan-gelatin network (HA/CS-Gel) composite of similar composition to that of normal human bone was prepared as a three-dimensional biomimetic scaffold by phase separation method for bone tissue engineering. Changing the solid content and the compositional variables of the original mixtures allowed control of the porosities and densities of the scaffolds. The HA granules were dispersed uniformly in the organic network with intimate interface contact via pulverizing and ultrasonically treating commercial available HA particles. Scaffolds of 90.6% porosity were used to examine the proliferation and functions of the cells in this three-dimensional microenvironment by culturing neonatal rat caldaria osteoblasts. Histological and immunohistochemical staining and scanning electron microscopy observation indicated that the osteoblasts attached to and proliferated on the scaffolds. Extracellular matrices including collagen I and proteoglycan-like substrate were synthesized, while osteoid and bone-like tissue formed during the culture period. Furthermore, the cell/scaffold constructs had good biomineralization effect after 3 weeks in culture.     

α-磷酸三钙/HA晶须/羧甲基壳聚糖-明胶复合增强多孔骨水泥的制备研究

为研究羟基磷灰石(HA)晶须和羧甲基壳聚糖-明胶(CMC-Gel)对多孔磷酸钙骨水泥(CPC)力学性能的影响,将α-磷酸三钙(α-TCP)粉、HA晶须和致孔剂L-谷氨酸钠按一定的质量比进行混合,加入调和液制备成α-TCP/HA晶须复合多孔骨水泥,然后将其浸润到一系列不同CMC和Gel质量比的溶液中以制备α-TCP/HA晶须/CMC-Gel复合增强多孔骨水泥,对其进行抗压强度测试和扫描电镜观察。结果显示,当HA晶须含量为4%,未添加CMC和Gel时,α-TCP/HA晶须复合多孔骨水泥的抗压强度达到2.57MPa,与未复合HA晶须的骨水泥相比提高了81%;当CMC和Gel的质量比为50∶50时,α-TCP/HA晶须/CMC-Gel复合多孔骨水泥的抗压强度达到最大值3.34MPa,与单纯的多孔α-TCP骨水泥相比提高了135%,同时韧性也有较大改善。     

Preparation and characterization of macroporous chitosan-gelatin/beta-tricalcium phosphate composite scaffolds for bone tissue engineering

A biodegradable composite scaffold was developed using beta-tricalcium phosphate (beta-TCP) with chitosan (CS) and gelatin (Gel) in the form of a hybrid polymer network (HPN) via co-crosslinking with glutaraldehyde. Various types of scaffolds were prepared by freezing and lyophilizing. These scaffolds were characterized by Fourier transform infrared, X-ray diffractometer, and scanning electron microscopy. The macroporous composite scaffolds exhibited different pore structures. Compressive properties were improved, especially compressive modulus from 3.9-10.9 MPa. Biocompatibility was evaluated subcutaneously on rabbits. A mild inflammatory response was observed over 12 weeks. The results suggest that the scaffolds can be utilized in nonloading bone regeneration.     

Preparation of antibacterial silver-doped silica glass microspheres

Various types of inorganic substances doped with silver ions have been developed as antibacterial materials, and some have already been commercialized. Colorless and chemically durable materials that slowly release silver ions are, however, still need to be developed. The present authors have previously shown that when a silica glass doped with silver and aluminium ions is prepared using the sol-gel method, the resultant product is colorless, chemically durable, and slowly releases silver ions into water over a long period. The doped silica glass takes a form of microspheres <1 microm in diameter, it is easily mixed with organic polymers, and the mixture can be formed into a thin film or fine fibers, etc. We report on the preparation of silver doped silica glass microspheres having a diameter =1 microm, using the sol-gel method. Initially, tetraethoxysilane was partially prehydrolyzed by water in ethanol, and then aluminium triisopropoxide was added to the solution to form Si-O-Al bonds. Finally, an ammonia solution containing silver nitrate was added to form silica microspheres doped with silver ion together with aluminium ions. The results show monodispersed microspheres 0.4-0.6 microm in diameter were obtained with nominal compositions of Si/Al/Ag = 1/0.01-0.03/0.003-0.03, with a molar ratio of Al/Ag = 1-3.3. The microspheres were colorless, showed a high chemical durability, and slowly released silver ions into water at 37 degrees C. Microspheres with the composition Si/Al/Ag = 1/0.01/0.01 showed excellent antibacterial activity against Escherichia coli. The minimum inhibitory concentration (MIC) of the microspheres was 400, which is less than the MIC value (800) of commercial antibacterial materials.