核-壳结构复相生物活性陶瓷微球优化制备及其抗菌性能评价

通过自主设计的同轴核-壳结构双层喷头及微流控系统,成功制备出一系列核-壳结构型多孔性生物活性硅酸钙基陶瓷微球,并通过对其核心层铜掺杂量的调控和外壳层微孔结构的剪裁,实现了该类微球核心层抗菌活性离子的可控缓释.采用X射线衍射分析明确了烧结后的陶瓷微球样品的物相组成和晶相结构.通过扫描电子显微镜观察发现使用该系统制备出的微球烧结后仍具有良好的球形形态及明确的核-壳结构,并且特定组分内部微孔结构符合设计要求.一系列模拟体内环境的微球浸泡实验系统研究了该类材料的体外离子释放行为和生物降解速率,研究结果显示该类陶瓷微球经特定层造孔后有快速的抗菌离子释放,并且释放速率可调可控.最后通过与金葡菌的体外共培养抑菌实验及细菌黏附实验等对微球的抗菌性能进行了研究,结果显示Cu10@Mg6-15μm组具有最佳的抑菌效果;优化壳层的多孔结构比单纯提高核层铜离子掺杂率更有利于活性离子释放.此次构建的壳层微孔优化型核-壳结构陶瓷微球,能够帮助解决抗感染离子可控缓释问题并带来长期抑菌的效果,为慢性骨髓炎等临床问题提供了潜在的治疗新材料.     

壳核结构纳米Fe包覆玻璃微珠复合材料的制备

以金属盐、柠檬酸和玻璃微珠等为原料,采用非均相沉淀-热还原法制备了纳米金属铁包覆空心玻璃微珠壳-核复合材料。采用SEM/EDS、XRD对包覆前后的复合微球进行了表征,分析了表面活性剂和加料速度对壳-核微球的形成、形貌和物相的影响。结果表明,在优化的工艺条件下,可以制备出晶粒尺寸约为50.2nm的纯铁均匀包覆的壳-核结构复合材料,包覆层显示出均匀、光滑和紧密的特点,包覆层Fe原子为体心立方结构。表面活性剂的加入提高了颗粒分散均匀性,促进了包覆层的形成。随着碳酸氢铵滴加速度的增大,引起均相沉淀的发生,在颗粒表面形成凸起。     

SiO_2/SiCN核壳陶瓷微球的制备及表征

采用乳液技术和先驱体转化法相结合,利用改性后SiO_2颗粒表面的双键引发聚硅氮烷(PSN)原位聚合,得到SiO_2/PSN核壳结构微球,经高温裂解过程成功制备SiO_2/SiCN核壳陶瓷微球。研究SiO_2与PSN原料的质量比、固化时间和热解温度对核壳微球形成过程和形貌的影响,并采用SEM,EDS,TEM,FT-IR,XRD对微球的微观形貌、化学成分及物相进行表征。结果表明:SiO_2与PSN质量比为1∶4时,200℃固化4h得到表面颗粒分布均一、包覆完全的SiO_2/PSN核壳微球;经800~1200℃热处理后,得到能保持原来形貌的非晶态SiO_2/SiCN核壳陶瓷微球;1400℃热解产物发生结晶,生成了SiO_2,SiC和Si_3N_4晶相。     

静电凝聚法制备苯乙烯-丙烯酸共聚物/氧化铈核壳纳米复合材料

致力于苯乙烯-丙烯酸共聚物(P(St-co-AA))微球/氧化铈核壳纳米结构的制备,以无皂乳液聚合制备的P(St-co-AA)微球为负电组成,水热法合成的氧化铈纳米粉体为正电组成,设计了静电凝聚法复合工艺,对复合工艺条件进行了初步的探索。结果表明:采用无皂乳液聚合制备的P(St-co-AA)微球呈正球形,颗粒尺寸均一,尺寸在160~390nm范围内可控;以CTAB为表面活性剂,采用水热法在100℃条件下成功制得了颗粒尺寸在10~20nm的氧化铈纳米粉体。在水溶液体系中,在静电凝聚作用下,所制备氧化铈在P(St-co-AA)微球表面紧密堆积,形成了P(St-co-AA)/氧化铈核壳结构。可通过调节P(St-co-AA)微球的尺寸与负电性以及复合过程中pH值来调控所得核壳结构形貌。正负颗粒电性的匹配是构筑核壳结构的关键,一味地增加颗粒表面正电性或负电性对于实现调控复合过程形成纳米核壳结构并非有利。当苯乙烯与丙烯酸单体比例为10∶1时所得P(St-co-AA)微球在pH 2.0~3.0下所得核壳结构形貌均一,分散性较好。     

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。     

SiO2@TiO2核壳微球和TiO2中空微球的制备及其光催化性能

以Stber法制备的单分散SiO_2微球为模板,率先采用静电吸附法和相吸附法相结合技术制备出SiO_2@TiO_2核壳结构微球。深入研究了pH值及煅烧温度对其结构和性能的影响。对SiO_2@TiO_2微球进行去核处理,得到TiO_2中空微球。通过降解常见工业污染物硝基苯来研究两种微球的光催化活性。采用XRD、SEM、TEM、BET、FT-IR对样品进行表征,用紫外-可见分光光度计测量硝基苯溶液降解前后的吸光度。结果表明,相同条件制备的TiO_2中空微球的比表面积比SiO_2@TiO_2微球的显著增大,最大为87m~2/g,导致TiO_2中空微球的光催化活性比SiO_2@TiO_2微球明显提高,对硝基苯的4h降解率可达95.2%。低于600℃处理得到的TiO_2壳层为锐钛矿相,呈孤岛状模式生长。温度升高到700℃时出现金红石相。在pH=9.0、600℃热处理3h条件下制备的SiO_2@TiO_2微球经去核处理所得到的TiO_2中空微球的壳层厚度最大,为25.4nm,且空心球的Ti-O-Si键随之消失。     

核壳结构有机/无机复合微球的制备与应用进展

根据核、壳的组成,核壳结构有机/无机复合微球可以分为2类:A类是核为无机材料,壳为高分子材料的核壳式结构;B类是核为高分子材料,无机材料作为壳层的核壳式结构.综述了B类复合微球的研究进展,详细讨论了复合微球的制备方法,如原位化学沉积法、溶胶-凝胶法、化学镀法、自组装法,并对各种制备方法的优缺点进行了总结,介绍了复合微球在轻质雷达吸波材料、光子晶体、生物医药载体材料、化妆品等领域的应用.最后指出了该研究领域未来的发展方向.     

水解FeCl_3制备单分散P(St-co-AA)/Fe_2O_3亚微核壳粒子

用液相沉积法制备了壳层均匀、包裹致密的单分散P(St-co-AA)/Fe2O3亚微核壳粒子。用XRD、TEM和FESEM表征了该类粒子的物相、形貌及微观结构。结果表明用该法制备的核壳粒子,其壳层为Fe2O3晶粒,且均匀地包裹在乳胶粒子表面形成草莓状结构;改变FeCl3溶液的用量和重复包裹次数能方便地调节P(St-co-AA)/Fe2O3亚微核壳粒子的壳层厚度。可通过煅烧法用该核壳粒子来制备形状完整的单分散亚微中空磁球。     

同轴电喷射法制备核壳结构聚乳酸载药微球

通过同轴静电喷射法制备核-壳结构聚乳酸载药微球。壳层流体为聚乳酸溶液,核层流体为药物水溶液,其中在核层流体中加入壳聚糖以达到在增加溶液电导率的同时改善聚乳酸的亲水性和功能性的目的。实验研究了核、壳层溶液浓度、流量、喷射电压以及接收距离等因素对微球形貌及结构的影响。研究结果表明,当控制实验条件为壳、核层流速比为3∶1,壳层溶液浓度与核层溶液浓度均为1%(质量浓度),喷射电压为20kV,接收距离为15cm,模型药物浓度2mg/mL时,可以得到粒径1μm左右、具有一定缓释效果的核壳结构载药微球,包封率为76.64%,载药量为7.11%。     

结构可控PMMA/PAN/PMMA三层核壳聚合物微球的制备与表征

采用多步无皂乳液聚合的方法合成了三层核壳结构的聚甲基丙烯酸甲酯/聚丙烯腈/聚甲基丙烯酸甲酯(PMMA/PAN/PMMA)聚合物微球。并通过改变单体加入量得到一系列不同结构的三层核壳微球。使用激光粒度仪、红外光谱、扫描电镜等对得到的三层微球进行表征。结果表明,制备的聚合物微球具有清晰的三层核壳结构,直径在300 nm~500nm之间;其第二层及第三层厚度可分别控制在15 nm~30 nm,40 nm~70 nm之间,较易实现了三层核壳聚合物结构的控制。     

Development of Fast-Dissolving Tablets of Flurbiprofen-Cyclodextrin Complexes

The present study was aimed at developing a tablet formulation based on an effective flurbiprofen-cyclodextrin system, able to allow a rapid and complete dissolution of this practically insoluble drug. Three different cyclodextrins were evaluated: the parent β-cyclodextrin (previously found to be the best partner for the drug among the natural cyclodextrins), and two amorphous, highly soluble β-cyclodextrin derivatives, i.e., methyl-β-cyclodextrin and hydroxyethyl-β-cyclodextrin. Equimolar drug-cyclodextrin binary systems prepared according to five different techniques (physical mixing, kneading, sealed-heating, coevaporation, and colyophilization) were characterized by Differential Scanning Calorimetry, x-ray powder diffractometry, infrared spectroscopy, and optical microscopy and evaluated for solubility and dissolution rate properties. The drug solubility improvement obtained by the different binary systems varied from a minimum of 2.5 times up to a maximum of 120 times, depending on both the cyclodextrin type and the system preparation method. Selected binary systems were used for preparation of direct compression tablets with reduced drug dosage (50 mg). Chitosan and spray-dried lactose, alone or in mixture, were used as excipients. All formulations containing drug-cyclodextrin systems gave a higher drug dissolved amount than the corresponding ones with drug alone (also at a dose of 100 mg); however, the drug dissolution behavior was strongly influenced by formulation factors. For example, for the same drug-cyclodextrin product the time to dissolve 50% drug varied from less than 5 minutes to more than 60 minutes, depending on the excipient used for tableting. In particular, only tablets containing the drug kneaded with methyl-β-cyclodextrin or colyophilized with β-cyclodextrin and spray-dried lactose as the only excipient satisfied the requirements of the Food and Drug Administration (FDA) for rapid dissolving tablets, allowing more than 85% drug to be dissolved within 30 minutes. Finally, it can be reasonably expected that the obtained drug dissolution rate improvement will result in an increase of its bioavailability, with the possibility of reducing drug dosage and side effects.     

硅灰石填充β-聚丙烯基复合材料的增强增韧

为了获得高韧性硅灰石填充β-聚丙烯基（W/β-PP）复合材料,采用负载庚二酸钙的硅灰石（β-W）填充聚丙烯（PP）制备。研究了W/β-PP复合材料中β-W的β-成核作用,并对比了硅灰石和β-W填充PP基复合材料的力学性能。结果表明:硅灰石填充聚丙烯（W/PP）复合材料主要形成α-晶,而β-W对PP结晶具有强的β-成核作用;W/PP复合材料的缺口冲击强度低于β-聚丙烯（β-PP）,硅灰石与PP的β-晶之间存在协同增韧作用,导致W/β-PP复合材料的缺口冲击强度高于β-PP;随着β-W含量的增加,W/β-PP复合材料的缺口冲击强度先增大后减小,在其质量分数为5%时达到最大值;同时硅灰石的增强作用可以提高β-PP的刚性。      

Fabrication and Characterization of Ca-Mg-P Containing Coating on Pure Magnesium

A biodegradable Ca-P coating mainly consisting of β-tricalcium phosphate(β-TCP) was fabricated on pure magnesium via the chemical deposition in a simulated Hank s solution.The method significantly accelerated the coating formation on magnesium.Moreover,the morphology,phase/chemical composition,the coating formation mechanism as well as degradation behavior in phosphate buffered saline(PBS) solution were investigated.Scanning electron microscopy(SEM) images showed that the coating had three layers and X-ray diffraction(XRD) patterns showed that the coating mainly contained Ca3(PO4)2 and(Ca,Mg)3(PO4)2.Electrochemical test showed that the corrosion current density(Icorr) of the coated Mg was decreased by about one order of magnitude as compared to that of pure magnesium.The immersion test indicated that the coating could obviously reduce the degradation rate.     

In Vitro Characterizations of PLLA/β-TCP Porous Matrix Materials and RMSC-PLLA-β-TCP Composite Scaffolds

To develop a novel degradable poly (L-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) bioactive materials for bone tissueengineering, β-TCP powder was produced by a new wet process. Porous scaffolds were prepared by three steps, i.e. solventcasting, compression molding and leaching stage. Factors influencing the compressive strength and the degradation behaviorof the porous scaffold, e.g. weight fraction of pore forming agent-sodium chloride (NaCl), weight ratio of PLLA: β-TCP,the particle size of β-TCP and the porosity, were discussed in details. Rat marrow stromal cells (RMSC) were incorporatedinto the composite by tissue engineering approach. Biological and osteogenesis potential of the composite scaffold weredetermined with MTT assay, alkaline phosphatase (ALP) activity and bone osteocalcin (OCN) content evaluation. Resultsshow that PLLA/β-TCP bioactive porous scaffold has good mechanical and pore structure with adjustable compressive strengthneeded for surgery. RMSCs seeding on porous PLLA/     

Effects of Grinding with Microcrystalline Cellulose and Cyclodextrins on the Ketoprofen Physicochemical Properties

Ground mixtures of ketoprofen (KETO) with native crystalline β-cyclodextrin, amorphous statistically substituted methyl-β-cyclodextrin, and microcrystalline cellulose were investigated for both solid phase characterization (differential scanning calorimetry (DSC) powder X-ray diffractometry, and infrared (IR) spectrometry) and dissolution properties (dispersed amount and rotating disk methods) to evaluate the role of the carrier on the performance of the final product. The effects of different grinding conditions, partial sample dehydration, and 1 year storage at room temperature were also investigated. The results pointed out the importance of the carrier nature on the efficiency of the cogrinding process. Both cyclodextrins were much more effective than was microcrystalline cellulose, even though no true inclusion complex formation occurred by mechanochemical activation. The best results were obtained from ground mixtures with methyl-β-cyclodextrin, which showed the best amorphizing and solubilizing power toward the drug and permitted an increase of approximately 100 times its intrinsic dissolution rate constant, in comparison with the approximate 10 times increase obtained from ground mixtures with β-cyclodextrin.     

改性β-环糊精微球的制备与表征

采用反相乳液聚合法制备β-环糊精(pCD)微球,再用顺丁烯二酸酐(MAH)改性制得丁烯二酸单酯化β-CD微球,探讨了不同工艺参数对改性β-CD微球粒径、分散性的影响.结果表明,在60℃的温度和200r/min～300r/min的电动搅拌,环氧氯丙烷(EPI)和β-CD的质量比为15∶1,复合乳化剂司盘-80和吐温-20...     

Inclusion complexes of fluorofenidone with β-cyclodextrin and hydroxypropyl-β-cyclodextrin

Background: Fluorofenidone is a novel antifibrotic drug and its aqueous solubility is low. Aim: This study was to prepare and characterize inclusion complexes of fluorofenidone (AKF-PD) with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Method: The AKF-PD/cyclodextrins (CDs) inclusion complexes were prepared by coprecipitation and freeze-drying, respectively. The solubility enhancement of AKF-PD was evaluated by phase solubility method. Inclusion complexation in solid phase was studied by X-ray diffraction (XRD) and differential thermal analysis (DTA). The dissolution profiles of AKF-PD/CDs inclusion complexes were investigated and compared with those of their physical mixtures and AKF-PD alone. Results: The phase solubility diagrams of AKF-PD with β-CD and HP-β-CD were of A_L-types, and the solubility of AKF-PD could be increased by 51.5% for β-CD at 0.014 M and 794.0% for HP-β-CD at 0.254 M. The results from XRD and DTA suggested that AKF-PD could form inclusion complex with β-CD or HP-β-CD. The dissolution rate of AKF-PD from the inclusion complexes was much more rapid than AKF-PD alone. Conclusions: The formulation of AKF-PD/CDs inclusion complexes showed superior performance in improving dissolution properties of AKF-PD.     

Synthesis of β-cyclodextrin functionalized gold nanoparticles for the selective detection of Pb2+ ions from aqueous solution

In the present study we carried out the synthesis of β-cyclodextrin (β-CD) functionalized gold nanoparticles (AuNPs) using a microwave assisted heating method in alkaline media. Stable dispersion of β-CD stabilized AuNPs was obtained at an optimized pH of 10.5. At this pH value the deprotonated secondary hydroxyl group of β-CD shows the highest chelating affinity toward Pb²⁺ ions thereby inducing AuNP aggregation. The Pb²⁺ induced aggregation in β-CD-AuNP solution is monitored by both colorimetric response and UV-Vis spectroscopy. TEM, DLS and FTIR analyses were carried out to confirm the Pb²⁺ ion induced aggregation behaviour of β-CD-AuNPs under alkaline conditions. Furthermore at the experimental pH the response of the β-CD-AuNP system towards Pb²⁺ ions is selective when compared with other interfering metal cations.     

生物陶瓷骨内植入后与组织间的界面研究

将β—TCP陶瓷植入大白兔的股骨内并定期注射四环素，分别在光学显微镜、荧光显微镜或扫描电子显微镜下观察新骨的形成和成骨过程，研究了β—TCP植入体内后与组织间的界面作用以及磷酸钙生物陶瓷的成骨作用．结果表明，在类骨质表面有大量的成骨细胞，间充质细胞增生和浸入．植入β-TCP陶瓷两个月后，类骨质通过钙化转变为编织骨．植入三个月后，出现由骨桥连接的“骨岛”，β—TCP陶瓷降解，并被新骨分散．植入六个月后，新的骨髓腔形成，编织骨变成板层骨．八个月后，在哈弗氏骨板上出现材料颗粒，形成典型的松质骨结构．因此，无生命的钙磷材料在体内可以参与有生命的组织活动．     

β-Cyclodextrin inclusion complex: preparation,characterization, and its aspirin release in vitro

In this work, the optimal clathration condition was investigated for the preparation of aspirin–β-cyclodextrin (Asp--β-CD) inclusion complex using design of experiment (DOE) methodology. A 3-level, 3-factor Box--Behnken design with a total of 17 experimental runs was used. The Asp--β-CD inclusion complex was prepared by saturated solution method. The influence on the embedding rate was investigated, including molar ratio of β-CD to Asp, clathration temperature and clathration time, and the optimum values of such three test variables were found to be 0.82, 49°C and 2.0 h, respectively. The embedding rate could be up to 61.19%. The formation of the bonding between--COOH group of Asp and O--H group of β-CD might play an important role in the process of clathration according to FT-IR spectra. Release kinetics of Asp from inclusion complex was studied for the evaluation of drug release mechanism and diffusion coefficients. The results showed that the drug release from matrix occurred through Fickian diffusion mechanism. The cumulative release of Asp reached only 40% over 24 h, so the inclusion complex could potentially be applied as a long-acting delivery system.