乳化／内部凝胶化工艺制备海藻酸钙凝胶微球的研究

从乳化/内部凝胶化制备海藻酸钙凝胶微球的机理入手,系统考察了制备工艺参数如油水比、表面活性剂添加量、碳酸钙添加量和冰乙酸添加量对海藻酸钙凝胶微球的球形度、粒径大小及分布、产率的影响规律.通过对该工艺参数的优化,能够制备出球形度良好,产率在85%以上,粒径分布均一的海藻酸钙凝胶微球.     

Fe3O4磁性液芯微胶囊的液化制备方法研究

探索了采用三步法制备液芯磁性微囊的新方法.采用喷雾法制备了磁性海藻酸钙微球,用激光粒度仪测得微球平均粒径为130/μm.通过合成脲甲醛树脂对磁性海藻酸钙微球进行包覆,详细研究了脲甲醛预聚和缩聚条件对包覆结果的影响.最后对脲甲醛树脂包覆后的磁性海藻酸钙微球进行液化,结果表明,在一段时间内,液化效果受柠檬酸钠溶液浓度和pH值影响明显;最终微囊液化效果良好,体积增大,内部的磁性粒子向囊心集聚.     

放射自显影海藻酸钙栓塞微球的制备

利用乳化-内部凝胶化法,将放射显影剂碘化油包封于海藻酸钙微球中.通过改变机械搅拌速率可以控制微球的粒径分布.碘化油/海藻酸钙微球可以作为栓塞制剂阻断患处血供,还可以兼具放射自显影的作用,有利于减少碘化油所导致的不良反应,方便治疗.     

PLLA/HA复合微球的制备

采用了一种新的微球制备方法液滴-冷凝法,以左旋聚乳酸[Poly(L-lactic-acid),PLLA]和羟基磷灰石(Hydroxyaptite,HA)为原料制备了复合微球。采用正交试验,以复合微球的粒径、球形度、成球率和孔隙率为考察指标,研究了PLLA溶液浓度、PLLA/HA质量比及冷凝液的温度梯度对复合微球成型和性能的影响,应用扫描电镜(SEM)对聚乳酸微球的微观形貌、孔隙结构进行了观察和表征。研究结果表明,应用该工艺制备的微球粒径均一,球径可控,其表面和内部都存在丰富的微孔,且孔间互相贯通。当采用较低浓度的PLLA溶液和适中的冷凝液温度梯度时,复合微球的各项指标均较好。该微球材料有望在骨缺损填充等领域得到应用。     

海藻酸钙/聚精氨酸微胶囊的制备及其生物相容性

以海藻酸盐、 聚精氨酸为壁材, 采用高压静电法制备了球形度好、 表面光洁、 粒径均匀的新型药物载体——海藻酸钙/聚精氨酸微胶囊。参照医疗器械生物学评价标准, 对其生物相容性进行了研究。细胞毒性试验结果显示, 当海藻酸钙/聚精氨酸微胶囊的含量为0.1、 0.5、 1.0 mg/mL时, 微胶囊对L929细胞生长无明显抑制作用, 海藻酸钙/聚精氨酸微胶囊浸提产物在10.0 mg/mL时仍无细胞毒性作用。海藻酸钙/聚精氨酸微胶囊不引起急性全身毒性反应, 不引起溶血反应。通过本组试验可见, 采用高压静电法制备的药物载体——海藻酸钙/聚精氨酸微胶囊具有较好的生物相容性, 具有开发和应用价值。     

液滴法在惯性约束聚变靶丸制备技术中的应用

综述了液滴法用于制备惯性约束聚变（ICF）物理实验靶丸中的历史、现状与发展，评述了液滴法制备玻璃微球、塑料微球、泡沫微球和金属微球的优缺点和弥补技术，初步探讨了液滴法作为ICF靶丸制备技术的方向。     

去甲斑蝥素PLA-PEG纳米微球的制备研究

采用复乳法和相分离法两种方法制备去甲斑蝥素的聚乳酸-聚乙二醇嵌段共聚物(PLA-PEG)纳米微球.对比了两种不同方法对制得的含药微球在粒径、包封率以及缓释性能方面的差异.用激光粒度分析仪表征了微球的粒径及其分布,并用透射电镜观察了微球的形貌,其结果表明:复乳法与相分离法制备的微球粒径均在100nm左右,并且成球性好;相对于复乳法,相分离法制备的微球分布较宽,包封率较高,可达到50%左右;体外释放实验表明两种方法制备的微球都具有缓释作用.     

基于不同载体的染料表面印迹复合微球及其识别性能

分别以三羟甲基丙烷三丙烯酸酯(TRIM)交联的聚甲基丙烯酸(PMAA)微球(PMAA-TRIM)、阳离子交换树脂、阴离子交换树脂和羟基磷灰石/海藻酸钙微球为载体,以甲基橙为模板,KH-570和KH-550硅烷为功能单体制备分子印迹复合微球。研究4种载体制备的印迹复合微球对甲基橙的吸附性能、印迹效率、识别选择性及重复使用性能。结果表明,甲基橙印迹复合微球对其模板具有较快的吸附速率和较大的吸附量。以PMAA-TRIM微球、阳离子交换树脂和阴离子交换树脂制备的印迹复合微球具有很好的重复使用性能。     

壳聚糖/海藻酸盐微胶囊膜的物质扩散性能研究

针对微囊化细胞三维培养研究背景,以壳聚糖、海藻酸钠为微载体制备材料,采用脉冲电场液滴工艺制备海藻酸钙微球,使之与壳聚糖溶液通过聚电解质络合反应生成选择透过性微囊膜.以传统细胞培养的重要碳源葡萄糖与柠檬酸、氮源L-谷氨酸为小分子模型,以聚乙二醇为测定微囊膜截留相对分子质量的模型分子,开展微胶囊传递性能研究.结果表明,葡萄糖、柠檬酸和L-谷氨酸可以自由透过微囊膜扩散,并且柠檬酸和L-谷氨酸能通过竞争螯合Ca2+引起微囊凝胶结构解聚;采用20 mg/mL海藻酸钠溶液与5万相对分子质量、2 mg/mL壳聚糖溶液制备微胶囊,囊膜的截留相对分子质量为1 500.     

基于微流控的海藻酸钙空心纤维的制备及其在细胞培养中的应用

海藻酸钙水凝胶空心纤维在药物传递、组织工程等领域具有潜在的应用价值。但传统的纤维制备方法,如静电纺丝或模具法等,很难或无法制备海藻酸钙空心纤维。本研究首先采用自制的两相微流控装置,连续制备出形貌均一稳定的海藻酸钙空心纤维,并通过显微镜和扫描电子显微镜(SEM)对其空心结构进行了表征。然后考察了装置中内相毛细管尖端管径、内外相流体流速比以及氯化钙浓度对空心纤维内外径尺寸和厚度的影响,结果表明,空心纤维的尺寸在一定范围内可以进行调控。最后将这种空心纤维应用于封装和培养L929成纤维细胞,结果表明,成纤维细胞存活率较高,并且有沿着空心纤维内壁成直线生长的趋势。这种方法为纤维状细胞的培养提供了一种思路。     

基于逆响应面法的有限元模型修正

基于响应面法（RSM）的有限元模型修正是以若干设计参数（如密度、弹性模量等）为自变量,以若干特征参数（如固有频率、振型等）为因变量,通过回归分析方法来拟合特征参数关于修正参数的显式表达式。提出的逆响应面法（IRSM）则是以特征参数作为自变量,设计参数作为因变量。利用此法的有限元模型修正可直接根据特征参数的目标值得到设计参数的修正量,而不需要经过迭代计算,有效地提高计算速度和精度。介绍逆响应面法及其应用,讨论使用响应面法和逆响应面法进行有限元模型修正的优缺点和适用范围,分析适合于逆响应面法的逆响应面函数、实验设计方案和回归精度检验的方法。利用逆响应面法对一简支梁进行有限元模型修正的结果表明,逆响应面法能高效准确地修正设计参数,对于输出变量少于输入变量的情况更能显著减少有限元计算次数,适用于复杂的工程结构。     

Formulation and in vitro evaluation of prolonged release floating microspheres of atenolol using multicompartment dissolution apparatus

The aim of the present work was to prepare floating microspheres of atenolol as prolonged release multiparticulate system and evaluate it using novel multi-compartment dissolution apparatus. Atenolol loaded floating microspheres were prepared by emulsion solvent evaporation method using 3² full factorial design. Formulations F1 to F9 were prepared using two independent variables (polymer ratio and % polyvinyl alcohol) and evaluated for dependent variables (particle size, percentage drug entrapment efficiency and percentage buoyancy). The formulation(F8) with particle size of 329?±?2.69 µm, percentage entrapment efficiency of 61.33% and percentage buoyancy of 96.33% for 12?h was the of optimized formulation (F8). The results of factorial design revealed that the independent variables significantly affected the particle size, percentage drug entrapment efficiency and percentage buoyancy of the microspheres. In vitro drug release study revealed zero order release from F8 (98.33% in 12?h). SEM revealed the hollow cavity and smooth surface of the hollow microspheres.     

茶多酚/壳聚糖/海藻酸钠纳米微球的制备

目的探讨各因素对制备茶多酚/壳聚糖/海藻酸钠纳米微球载药率、包埋率的影响,研究纳米微球体外释放行为,为后期缓释抗菌膜的制备提供基础。方法采用单因素实验、正交实验考察海藻酸钠溶液浓度、壳聚糖溶液浓度、CaCl_2溶液浓度、茶多酚溶液浓度对纳米微粒载药率、包封率的影响,并考察其体外释放率。结果当海藻酸钠溶液、壳聚糖溶液、CaCl_2溶液、茶多酚溶液的质量浓度分别为15,10,15,0.8 mg/m L时,该工艺条件下制备的纳米微粒载药率为22.71%,包封率为61.38%,且粒径集中在500 nm左右,有较好的缓释效果。结论所得的最佳工艺制备条件为后期做缓释抗菌膜打下良好基础。     

多壳层化中空微球两相陶瓷生物材料制备研究

利用硅灰石(CaSiO₃)和β-磷酸三钙(β-TCP)在骨损伤环境中降解速率存在显著性差异的基本特性, 以海藻多糖凝胶球为模板, 运用层-层包裹方法构建CaSiO₃、β-TCP交替包裹的多壳层化中空微球。首先, 将海藻酸钠与硅酸钠的混合水溶胶逐滴加入到温和搅拌的硝酸钙水溶液中, 形成由水合硅酸钙盐为壳层的海藻多糖基复合微球, 然后将该复合微球依次浸入到含β-TCP的海藻酸钠溶液和含CaSiO₃的海藻酸钠溶液中, 温和搅拌后将微球悬浮液分离, 再经真空冷冻干燥和850℃煅烧处理, 从而获得以CaSiO₃为最内壳层并具有双壳层或三壳层的中空微球。按类似步骤也可以制备以β-TCP为最内壳层的多壳层中空微球。运用SEM、EDX、XRD和FTIR对该类微球的微结构和组成进行了分析。运用弱酸性Tris缓冲液(pH=5.2)对双壳层中空微球的降解。实验证明, 缓冲液中硅、磷浓度变化特征与其外壳层、内壳层化学组成(即β-TCP或CaSiO₃)密切相关。本研究结果对构建降解速率阶段可调的复合陶瓷多孔生物材料以及研究原位骨再生效率与孔道网络演化规律之间关系等具有重要学术价值。     

Evaluation and optimization of preparative variables for controlled-release floatable microspheres prepared by poor solvent addition method

The aim of this study was to evaluate and optimize preparative parameters for floatable theophylline microspheres prepared by the emulsion-solvent evaporation method. A three-factor three-level Box-Behnken design was employed using amount of poor solvent, temperature-increase rate and drug loading as independent factors, and percentage floating at 3 h and time required for 50% drug release as dependent variables. Simultaneous optimization of the parameters for maximum buoyancy and desirable drug release was conducted using a partitioned artificial neural network. A microsphere using 27.6% of drug loading, 0.29 degrees C/min of temperature-increase rate, and 1.7 mL of poor solvent was identified for maximizing buoyancy and sustaining drug release.     

Optimization of properties of fly ash aggregates for high-strength lightweight concrete production

The optimization of properties of lightweight fly ash aggregates for suitability in high-strength lightweight fly ash concrete production was investigated using response surface methodology (RSM). Design-Expert software was used to establish the design matrix and to analyze the experimental data. The relationships between the sintering parameters (temperature, binder content and binder type) and experimentally obtained three responses (specific gravity, water absorption and crushing strength) were established. Also, the optimization capabilities in Design-Expert software were used to optimize the sintering process. Historical data design technique under RSM was performed to optimize the input parameter interactions which showed the best conditions for preparation of fly ash pellets. According to the obtained results, the developed models are statistically accurate and can be used for further analysis. The experimental values agreed with the predicted ones, thus indicating suitability of the model employed and the success of RSM in optimizing the sintering conditions.     

Preparation and optimization of a novel microbead formulation to improve solubility and stability of curcumin

Curcumin is an active ingredient which is poorly water-soluble, leading to a low oral bioavailability. The aim of this research was to prepare a novel microbead formulation, and to solubilize, solidify, and improve storage stability of curcumin. Firstly, curcumin was solubilized with Kolliphor^TM RH40 and then microencapsulated by cross linking of sodium alginate with calcium chloride. A three-factor, three-level Box–Behnken design was employed to acquire the optimum microbead formulation, namely the best entrapment efficiency and in vitro curcumin release. The independent variables were sodium alginate concentration, calcium chloride concentration, and the weight of curcumin solution, while the dependent variables were entrapment efficiency and in vitro curcumin release. The optimized microbead formulation was 2.06% sodium alginate, 24.33% calcium chloride, and 1.28 g curcumin solution (containing curcumin and RH40 with a ratio of 1:22, g/g). Results showed that high concentrations of sodium alginate and calcium chloride could increase the entrapment efficiency. In vitro curcumin release decreased with increasing of sodium alginate as well as decreasing of calcium chloride. In conclusion, the optimum microbead formulation increased the solubility of curcumin and enhanced its stability, and achieved a high entrapment efficiency and in vitro curcumin release.     

Modeling and optimization of electrospun polyvinylacetate (PVAc) nanofibers by response surface methodology (RSM)

Response surface methodology (RSM), a collection of statistical and mathematical techniques, has been widely used to optimize and design operating conditions. Although this method is suitable for optimizing experimental conditions, very few attempts have been made on the electrospinning process. In this work, RSM was used to model and optimize of the electrospinning parameters for polyvinylacetate (PVAc) nanofibers. PVAc solution in acetone was electrospun under various conditions such as concentration of spinning solution and applied voltage. The experimental results indicate that concentrations of solution and applied voltage played an important role on the diameter size of PVAc nanofibers. The second order polynomial function was used to correlate the fiber diameter with the production variables. The predicted fiber diameters were in good agreement with the experimental results.     

Evaluation and Optimization of Preparative Variables for Controlled-Release Floatable Microspheres Prepared by Poor Solvent Addition Method

The aim of this study was to evaluate and optimize preparative parameters for floatable theophylline microspheres prepared by the emulsion–solvent evaporation method. A three-factor three-level Box–Behnken design was employed using amount of poor solvent, temperature-increase rate and drug loading as independent factors, and percentage floating at 3 h and time required for 50% drug release as dependent variables. Simultaneous optimization of the parameters for maximum buoyancy and desirable drug release was conducted using a partitioned artificial neural network. A microsphere using 27.6% of drug loading, 0.29°C/min of temperature-increase rate, and 1.7 mL of poor solvent was identified for maximizing buoyancy and sustaining drug release.     

Calcium Alginate Microspheres of Bacillus subtilis

Microspheres of Bacillus subtilis were prepared using sodium alginate. Some typical properties of microencapsulated systems, such as microorganism content, particle size, and germination time, were studied. Calcium alginate microspheres were obtained by the emulsification method, dripping into a solution of calcium salt. The conditions of the preparation steps were very soft to produce calcium alginate microspheres containing cells with no apparent changes in general biological properties. The hydrogel matrix provides protection without preventing communication with the surrounding medium.