聚苯乙烯-孕酮免疫微球的新法制备与检测

本研究采用改进的无乳化剂乳液聚合法制备聚苯乙烯微球,并对聚合反应温度和有机溶剂含量对聚合反应和粒径的影响进行了研究;再将合成的聚苯乙烯微球与孕酮抗体反应,结果表明通过加入少量有机溶剂,提高了聚合反应速度和转化率,制备出了粒径可控的单分散聚苯乙烯免疫微球,粒径在200～800nm之间,微球具有较高的抗体结合容量,且结合后保持了较高的抗体活性.用合成的孕酮免疫胶乳进行免疫凝集实验,观察了反应时间,反应温度的影响,确定了免疫反应的基本反应条件.     

普鲁兰多糖微球制备及影响因素考察

目的 采用水／油（W／O）乳化交联法制备普鲁兰多糖微球并观察多种因素对微球形态及粒径的影响。方法采用W／O乳化交联法，司班20作为表面活性剂，分别以蓖麻油和正己烷作为油相，不同浓度的普鲁兰多糖水溶液为水相，形成均一乳液后加入交联剂戊二醛，普鲁兰多糖被固化形成微球。观察普鲁兰多糖水溶液浓度、水／油比例、交联剂浓度、转速等多种因素对微球形态及大小的影响。通过扫描电镜观察微球形态，Mastersizer S激光粒度仪进行粒径分析。结果油的成分、水／油比例、多糖水溶液浓度、交联剂浓度及搅拌速度均不同程度影响微球形态和大小。蓖麻油为油相形成微球条件：水／油＜1：5，普鲁兰多糖水溶液浓度1％，交联剂浓度5％～50％。这些条件下形成微球表面光滑、粒径分布均一。正己烷为油相形成微球条件：1：5＜水／油＜1：2，普鲁兰多糖水溶液浓度1％，交联剂浓度＜25％，形成微球表面光滑，但粒径分布不均一。0．2％或5％普鲁兰多糖水溶液、转速＜200r／min均不能形成微球。结论采用W／O乳化交联法能够制备普鲁兰多糖微球，这种制备方法简单，多种因素控制微球形态与大小。     

两性霉素B缓释微球的制备及缓释性能研究

为了更好地研究药物载体材料对药物微球缓释性能的影响,本研究将可完全生物降解的共聚物作为壁材以相分离法制备含抗真菌药物两性霉素B的微球,研究了不同溶剂/非溶剂、不同分子量共聚物、不同配比共聚物、不同表面活性剂及其不同用量等因素对微球的粒径大小、分布、药物包封率和药物体外释放等性能的影响。使用透射电镜（TEM）和原子力显微镜（AFM）观察微球的表面形貌,使用激光粒度分析仪测试微球的粒径大小及分布,使用紫外分光光度计测定药物的包封率。研究发现,聚合物特性粘度和分子量越大,聚合物中LA：PEG的配比越大,微球粒径越大,分布越宽;微球粒径越大,包封率也较大;AmB/PLA-PEG微球具有缓释性能,且含药微球的释放性能与微球的粒径,包封率等因素有关。     

聚苯乙烯—孕酮免疫微球的新法制备与检测

本研究采用改进的无乳化剂乳液聚合法制备聚苯乙烯微球，并对聚合反应温度和有机溶剂含量对聚合反应和粒径的影响进行了研究；再将合成的聚苯乙烯微球与孕酮抗体反应，结果表明通过加入少量有机溶剂，提高了聚合反应速度和转化率，制备出了粒径可控的单分散聚苯乙烯免疫微球，粒径在２００～８００ｎｍ之间，微球具有较高的抗体结合容量，且结合后保持了较高的抗体活性。用合成的孕酮免疫胶乳进行免疫凝集实验，观察了反应时间，反应温度的影响，确定了免疫反应的基本反应条件。     

喷雾干燥法制备眼用壳聚糖/明胶复合微球**

背景：普通滴眼液由于泪液冲刷与鼻泪管吸收等因素,在眼表停留时间短,生物利用度低。 目的：以壳聚糖、明胶为载体材料,左氧氟沙星为模型药物,制备应用于眼表的缓控释微球并考察其理化性质与体外释放。 方法：采用喷雾干燥法制备左氧氟沙星壳聚糖/明胶微球,通过扫描电镜观察微球的表面形态,激光粒度仪测量微球粒径分布与zeta电位,高效液相色谱法检测微球的载药率与包封率,动态透析法研究微球体外药物释放情况。 结果与结论：所得微球形态良好,粒径分布窄,平均粒径为(1 267.4±115.3) nm,zeta电位为+(32.19±0.85) mV,载药量为(18.31±0.22)%,包封率为(91.53±1.12)%。载药微球体外释放符合一级释药方程Ln(1-Q)=-0.699 1t-0.086 4,r2=0.945 1。说明壳聚糖/明胶载药微球对左氧氟沙星具有缓释作用。实验采用喷雾干燥法成功制备了粒径及分布适宜、释放周期较理想、药物稳定性好的载左氧氟沙星壳聚糖明胶缓释微球。      

分散剂对悬浮法制备聚苯乙烯的影响及形貌分析

背景:聚苯乙烯微球由于其比表面积大、吸附性强、力学性能好、反应性强、表面活性大以及可回收等特点,在固相有机合成、生物医用、高分子吸附、固载催化剂等方面有着广泛的应用前景。因此,根据市场需要,生产适当粒度的聚苯乙烯微球是日常工艺控制的一项重要工作。目的:观察分散剂用量、分散剂种类以及分散剂加入次数对聚苯乙烯微球分散性能的影响。方法:以水为分散介质,在不加任何稳定剂的条件下,通过悬浮聚合法制备聚苯乙烯。称取各实验条件下的聚苯乙烯0.5g,依次数出0.5g的聚苯乙烯所含有的颗粒数,则相同质量的聚苯乙烯颗粒,颗粒数越多说明其颗粒尺寸越小。松下数码照相机观察聚苯乙烯颗粒的表面形貌及粒径分布。结果与结论:①随着分散剂用量的增加,聚苯乙烯的颗粒数也在增加,尤其当分散剂用量在0.8g和1.0g时,颗粒数增加幅度较大,从形貌图上可以看出颗粒尺寸急剧减小。②单独使用聚乙烯醇时随聚乙烯醇用量的增大,颗粒数显著增多,从形貌图上可以看出颗粒尺寸急剧减小,说明其具有良好的分散效果;单独使用磷酸钠或使用聚乙烯醇和磷酸钠的复合分散剂时,随着分散剂用量的增大,颗粒数反而减少,从形貌图上可以看出颗粒尺寸显著增大。③随着分散剂加入次数的增加,相同质量下聚苯乙烯的颗粒数也在增加。说明增加分散剂的补加次数,能在一定程度上增大分散剂的分散效果。     

用于组织工程骨的磁性聚乳酸乙醇酸共聚物-骨形态发生蛋白2微球的合成及检测*

背景：组织工程骨支架常因支架材料的孔隙率不佳和无法以合适的方式提供生物活性因子给种子细胞,导致支架对细胞的黏附及诱导性不强,成骨效率低下。 目的：合成一种新型的可用于组织工程骨的磁性聚乳酸乙醇酸共聚物-骨形态发生蛋白2缓释微球并对其各项性能进行检测分析。 方法：复乳法合成磁性聚乳酸乙醇酸共聚物-骨形态发生蛋白2微球。 结果与结论：扫描电镜下可见微球呈正圆形,粒径10~100 μm;激光共聚焦显微镜下可见重组人骨形态发生蛋白2在微球上分布均匀;振动样品磁强计检测结果显示微球具有超顺磁性;微球载药量为(1.00±0.18) μg/g;微球对其具有缓释效果;经45 ℃处理微球后测得微球载药量为(0.98±0.20) μg/g。说明合成的磁性聚乳酸乙醇酸共聚物-骨形态发生蛋白2缓释微球具有一系列良好的特性,为新型磁性组织工程骨支架的研制奠定了基础。      

一种新型热敏聚乳酸微球的制备与表征

背景：目前,基于聚乳酸的智能型微球是药物可控释放研究领域的热点。 目的：制备一种温度响应可控、生物可降解的微球载体。 方法：以甲基丙烯酸-2-羟乙酯作为丙交酯开环的引发剂,采用辛酸亚锡作为催化剂,并调节乳酸与甲基丙烯酸乙酯的比例,得到了不同分子质量的带双键聚乳酸(PDLLA-EMA)。以甲苯为溶剂,采用溶液合成法,自由基反应引发含有双键的聚乳酸以及N,N-异丙基丙烯酰胺共聚,成功制得了可降解温敏型共聚物(PNIPA-g-PDLLA-EMA)。采用复乳法,将PNIPA-g-PDLLA-EMA制成了微球。 结果与结论：实验制得PNIPA-g-PDLLA-EMA材料的热响应温度范围为35~42 ℃,基于该材料制得的微球粒径范围为(13.70±0.70)~(28.90±0.50) μm,粒径变化率为(138.7±4.20)%~(170.0±10.00)%,与同类材料相比,该微球已具备了应用于生物医学的潜在条件。关键词：智能型微球;可生物降解;聚乳酸;制备;载体 缩略语注释：PNIPAm：Poly N-isopropylacrylamide,聚(N-异丙基丙烯酰胺) doi:10.3969/j.issn.1673-8225.2012.16.015     

幽门螺杆菌全菌蛋白抗原壳聚糖微球体外释放特性

背景：不同方法制备出的幽门螺杆菌全菌蛋白抗原壳聚糖微球,其包裹率和控释效果也不同。 目的：探讨幽门螺杆菌全菌蛋白抗原壳聚糖微球的最佳制备方案,观察其体外释放特性。 方法：使用Berthold沉淀法制备壳聚糖微球,筛选最佳制备方案;使用扫描电镜及粒径分析仪观察壳聚糖微球的形态及粒径分布;冻干后的壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原,使用BCA蛋白定量试剂盒测量分析微球的抗原包裹率、包裹量及释放率。 结果与结论：从32种壳聚糖微球制备方案中筛选出了以海得贝壳聚糖为原料、冰乙酸的浓度为1%、硫酸钠为沉淀剂、pH值为5.0、不进行超声处理方案为最佳制备方案,扫描电镜示微球光滑圆整、致密,粒径分布在1.0~5.0 μm;抗原包裹率为79.92%,包裹量为16.47%;体外释放实验表明,总抗原释放率为20.39%,呈缓慢释放状态。     

包裹钆对比剂的PLGA微球研究初步

目的：制备包裹钆对比剂的PLGA微球,并评价PLGA微球在磁共振成像中的肾靶向增强效果。方法：Gd-DTPA作为内水相,溶入了PLGA的二氯甲烷有机溶剂作为油相,PVA-0486的水溶液作为外水相,采用复乳法制备包裹钆对比剂的PLGA微球;通过激光粒度分析仪测量微球平均粒径,用等离子体原子发射光谱仪测量微球载药量,并用磁共振成像仪观察微球的肾靶向增强效果。结果：PLGA浓度越大,PVA的浓度越小,合成的PLGA微球的平均粒径越大;PLGA微球对小鼠肾脏有明显的靶向增强作用。结论：包裹钆对比剂的PLGA微球有望成为一种能临床应用于磁共振成像的肾靶向对比剂。     

不同分散介质研磨所得纳米珍珠粉的比较

文题释义：纳米材料：物质结构在三维空间中至少有一维处于纳米尺度，或由纳米结构单元构成的且具有特殊性质的材料。在最新的一项纳米碳酸钙标准中，要求颗粒平均粒径≤100 nm。 纳米珍珠粉：以无水乙醇或水作为分散介质球磨细化珍珠粉，研磨介质为0.1 mm氧化锆球，通过扫描电镜、透射电镜、X射线衍射仪检测分析珍珠粉粒径，珍珠粉平均晶粒、平均粒径<100 nm，属于纳米材料。 背景：为了保留更多的有机质及材料生物学活性，需通过物理方法研磨细化珍珠粉。球磨法可以最大限度地保留珍珠粉中的有机质及其活性，而不同分散介质球磨制备的纳米材料效果不同。 目的：对以蒸馏水和无水乙醇两种分散介质研磨所得的纳米珍珠粉进行对比。 方法：分别以无水乙醇与水作为分散介质研磨制备纳米珍珠粉，采用扫描电镜、透射电镜、X射线衍射仪、凯氏定氮法及食品中氨基酸测定等方法比较分析研磨前后的珍珠粉。 结果与结论：①以无水乙醇为分散介质制备的纳米珍珠粉主要为类圆形颗粒，大小不等，主要分布在30-50 nm，平均晶粒20 nm，方解石碳酸钙相对百分比增至7%，蛋白质和氨基酸含量未发生明显变化；②以蒸馏水为分散介质制备的纳米珍珠粉主要为类圆形颗粒，存在较大的条状或块状不规则颗粒，大小不均，平均晶粒30 nm，方解石碳酸钙相对百分比增至10%，蛋白质和氨基酸含量有所减少；③结果表明两种分散介质研磨后珍珠粉粒度有明显差异，以无水乙醇为分散介质研磨的珍珠粉粒度更细更均匀。 ORCID: 0000-0002-9436-3464(毛秋华) 中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程     

Degradation and drug release characteristics of monosize polyethylcyanoacrylate microspheres

—Monosize, biodegradable poly(ethylcyanoacrylate) (PECA) microspheres with a diameter of 1.3μm were prepared by a relatively new polymerization method, the so-called phase inversion polymerization. The effects of pH and temperature on the degradation behavior of PECA particles were investigated. PECA microspheres were degraded mainly by surface erosion. The degradation rate increased with increasing pH temperature. A model drug, i.e. 2,4-dinitrophenylhydrazine (DNPH) was loaded into the monosize PECA microspheres during polymerization. The drug incorporation into the PECA microspheres increased with increasing initial drug concentration in the monomer phase. Drug release from the PECA microspheres was investigated at different pH. Higher drug release rates were observed in the neutral and alkaline media as compared with the acidic medium.     

Encapsulation of Carbon Black by Miniemulsion Polymerization

Full Paper: In this paper the effective encapsulation of carbon black with polymers by co‐sonication of a carbon black dispersion and a typical miniemulsion polymerization recipe is described. The carbon containing polymer particles are analyzed in detail by particle size measurements, transmission electron microscopy, density distributions experiments with the ultracentrifuge, and by nitrogen adsorption. The final particle size was in the range of 50 to 170 nm, the weight ratio polymer to carbon was changed between 20 : 80 and 90 : 10. In all cases, the surface tension of the final dispersion is above the minimal surface tension of SDS indicating the absence of micelles and the incomplete coverage of the polymer coated carbon particles with surfactant. The amount and type of an added hydrophobe needed for osmotic stabilization as well as the type of monomer have a large influence on the encapsulation process. The encapsulation process can be described by a scenario where the fusion/fission by ultrasound splits the monomer droplets, whereas the monomer coated carbon stays intact. The thickness of the monomer film depends on the amount of monomer and has to be optimized since there is an optimal range of monomer layer thickness in order to preserve the morphology. Too low amounts of monomer result in incompletely covered particles which aggregate with polymer whereas too much monomer results in the formation of a second species of pure polymer particles. The process can be described as a polymerization in an adsorbed monomer layer created and stabilized as a miniemulsion (“ad‐miniemulsion polymerization”).     

Core-shell microspheres by dispersion polymerization as promising delivery systems for proteins

Functional poly(methyl methacrylate) core-shell microspheres were prepared by dispersion polymerization. An appropriate selection of experimental parameters and in particular of the initiator and stabilizer amount and of the medium solvency power allowed a monodisperse sample as large as 600 nm to be prepared. To this purpose, low initiator concentration, high steric stabilizer amount and a low solvency power medium were employed. The microspheres present a core-shell structure in which the outer shell is constituted by the steric stabilizer which affords carboxylic groups able to interact with basic proteins, such as trypsin, whose adsorption is essentially driven by the carboxylic group density in the microsphere shell. Finally, fluorescent microspheres were prepared for biodistribution studies and shown to be readily taken up by the cells both in vitro and in vivo. These results suggest that these microspheres are promising delivery systems for the development of novel protein-based vaccines.     

Polymeric Microspheres for Immunoresearce

New microspheres having functional aldehyde groups have been prepared by radiation polymerization of acrolein solution containing hydroxyethyl methacrylate and glutalardehyde. The size distribution in the microspheres was narrow and average particle diameter was 1-2 μm. The binding ability of the microspheres to antigen increased by increasing the concentration of glutalardehyde. The preparation procedure of the microspheres is simple. The microspheres can be used for immunoresearch.     

Cibacron blue F3G-A-attached uniform and macroporous poly(styrene-co-divinylbenzene) particles for specific albumin adsorption.

Cibacron blue F3G-A-carrying uniform macroporous particles were proposed as an alternative sorbent for specific albumin adsorption. These particles were produced by a multistep polymerization procedure. In the first step of production, the uniform polystyrene seed particles were prepared by a dispersion polymerization method. Next. the polystyrene seed particles were first swollen by dibutylphthalate and then by styrene-divinylbenzene mixture in an aqueous emulsion medium. In the last step (i.e. repolymerization), styrene-divinylbenzene mixture was copolymerized within the swollen seed particles in the absence or presence of a stabilizer (e.g. poly(vinyl alcohol)). Although a considerable amount of non-specific BSA adsorption was observed on the surface of the particles produced in the absence of PVA, zero non-specific albumin adsorption could be achieved with the uniform macroporous particles produced in the presence of PVA. The stabilizer on the particle surface was also used as a ligand in the further derivatization of macroporous particles for specific albumin adsorption. Cibacron blue F3G-A was then covalently attached onto the surface of uniform macroporous particles. Specific albumin adsorption capacities up to 93 mg g(-1) could be achieved with the cibacron blue F3G-A-carrying macroporous particles of 6.25 microm in size.     

Suspension polymerization of 2-hydroxyethyl methacrylate in the presence of polymeric diluents: a novel route to spherical highly porous beads for biomedical applications

Spherical, highly porous beads of poly(2-hydroxyethyl methacrylate) (PHEMA) cross-linked with ethylene glycol dimethacrylate (EGDM) were prepared by suspension polymerization of HEMA in concentrated NaCl solutions in presence of toluene, poly(methyl methacrylate) (PMMA) in toluene, and poly(tetramethylene glycol) (PTMG). Magnesium hydroxide prepared in situ in the dispersion medium gave the best stabilization effect for the monomer droplets. In the presence of PTMG, beads having nearly 1.0 mm in diameter could be prepared, while toluene alone as the diluent produced beads of very small size. Removal of PMMA or PTMG from the beads after polymerization using suitable solvents gave rise to highly porous PHEMA microspsheres. Polymerization in the presence of PTMG produced microspsheres with better spherical geometry as compared to those generated in the presence of PMMA. The effect of various factors such as NaCl concentration, concentration of Mg(OH)2, and the concentration of PMMA or PTMG in the monomer phase on the stability of the suspension and the particle size distribution was investigated.     

Preparation of Highly Charged,Monodisperse Nanospheres

A two‐stage shot growth emulsifier‐free polymerization was applied to prepare styrene(St)/sodium styrenesulfonate (NaSS) latices. The latex particles prepared in the pure water medium were monodisperse and highly charged spheres, but their particle diameters were all higher than 120 nm. By using the two‐stage shot growth copolymerization at 70°C in the mixed reaction medium of water and acetone, we successfully prepared monodisperse, highly charged nanospheres with the smallest particle diameter of 89 nm. As the acetone content in the mixed reaction medium was increased to an acetone/H₂O ratio of around 0.125, the particle diameter decreased to minimum, and then the particle diameters increased with increasing acetone content in the mixed reaction medium. The conversion‐time curves for the first stage emulsifier‐free copolymerization of St/NaSS in the mixed reaction medium with varied acetone contents show that the polymerization rate first increased with increasing acetone content, and then decreased. The enhanced rate of polymerization in the lower acetone content results from the increase in the number of primary particle in the reaction medium. As the acetone content was further increased, the solubility of St in the reaction medium further increased, making the copolymerization somewhat like the dispersion polymerization and thus causing increased particle size.     

Emulsion polymerization of styrene with sodium hexadecyl sulphate/hexadecanol mixtures as emulsifiers. Initiation in monomer droplets

Part 1 describes the emulsification of styrene with mixtures of sodium hexadecyl sulphate (SHS), and hexadecanol (HD). Addition of HD led to a much better emulsification than with the anionic emulsifier alone. The effect of the fatty alcohol depended strongly upon the method of preparation of the emulsion. To obtain a fine dispersion of styrene it was necessary to treat the anionic emulsifier and the fatty alcohol with water at an elevated temperature prior to the addition of styrene. In this way emulsions with droplet sizes in the range of 0,5–1 μm could be prepared with relatively small amounts of fatty alcohol and with moderate stirring. The finely dispersed monomer emulsions produced by this method were capable of adsorbing the major part of the anionic emulsifier. Part 2 describes emulsion polymerization experiments with mixtures of SHS and HD. With emulsifier systems providing the most effective emulsification, the monomer droplets became the main loci for particle initiation and polymerization. Evidence for this hypothesis was provided by the bimodal dispersion of the latex particles, the major part being particles with a size distribution similar to that of the monomer droplet emulsion. The results of the kinetic investigations provided additional arguments for a mechanism involving initiation and polymerization in monomer droplets.