生物降解聚酯包埋利福平缓释微球的制备及释放行为

以生物可降解乙交酯和丙交酯的无规共聚物(PLGA)为载体,将抗结核病药利福平溶解于PLGA的有机溶液中,采用通常乳化-溶剂挥发方法制备了药物缓释微球.研究了影响微球制备的工艺条件.用电子显微镜观察了微球及降解后的表面形态,测定了微球粒径及载药量,评价了载药微球的体外释放行为.结果表明,以质量分数为1%的明胶为稳定剂,制备的微球形态完整,粒径范围为10～30μm,微球中利福平的平均质量分数为24.3%.体外释药时间可以通过高分子的降解速率来调控,本实验的释药时间可以在42～84d之间调控,药物缓释达到了理想的零级动力学释放.因此,利福平PLGA微球具有显著的长效、恒量药物缓释作用.     

PLA/MSM缓释微球的制备及生物活性

采用膜乳化-液中干燥法制备出担载二甲基砜(MSM)的聚乳酸(PLA)微球(PLA/MSM), 并研究了膜孔径、 搅拌转速和MSM浓度对载药微球形貌、 尺寸、 载药量、 体外释放及细胞活性的影响; 采用场发射环境扫描电子显微镜(ESEM)观察微球形貌、 尺寸及分布, 用等离子体发射光谱(ICP-AES)法检测PLA/MSM微球载药量、 包封率及体外释放, 采用ESEM观察微球内部结构, 并通过体外细胞培养和噻唑蓝(MTT)法检测MC-3T3-E1细胞的增殖能力. 研究结果表明, 膜乳化法制备的载药微球规整, 呈典型的圆球状, 表面光滑, 内部有多孔结构. 当膜孔径为5.1 μm且搅拌转速为500 r/min时, PLA/MSM微球大小更为均一; 当体系中MSM质量分数为8.6%时, 载药量可达到77.43%. 随着膜孔径减小及药物浓度的增加, 体外释放速率加快, 但初期均无明显的突释现象, 约10 d后累积释放量达到89.2%. 细胞实验结果显示, 在膜孔径为5.1 μm且MSM质量分数为8.6%的条件下, 制备的载药微球在细胞培养7 d时表现出明显的促增殖作用.     

聚L-谷氨酸担载胰岛素口服微球的制备与评价

以聚L-谷氨酸为载体材料, 采用无水乳液法制备了口服胰岛素微球, 微球直径在5~20 μm, 载药质量分数为5%~9%. 载药微球具有良好的pH敏感释放行为, 在胃模拟液中2 h释放量约为5%, 在肠道模拟液中2 h释放90%以上. 考察聚合物分子量、溶液浓度、理论投药量及混合材料对微球释放行为的影响.     

一步法制备PNIPAAm-g-PAN/PSt载银复合微球及其抗菌性能研究

以AgNO3为金属源,通过乙醇将与聚N-异丙基丙烯酰胺接枝聚丙烯腈/聚苯乙烯（PNIPAAm-g-PAN/PSt）聚合物微球表面酰胺基团配位的银离子（Ag+）还原,一步法制备了PNIPAAm-g-PAN/PSt载银复合微球。通过傅立叶变换红外（FTIR）和紫外-可见光光谱表征发现,由Ag+还原所得的Ag纳米颗粒被成功地固载在PNIPAAm-g-PAN/PSt 微球上;用透射电子显微镜（TEM）对载银微球的大小和形态进行了表征;热重分析（TGA）结果表明,固载在微球表面的银纳米颗粒的含量（质量分数）为12%;抗菌实验结果表明,所制备的载银微球具有抗革兰氏阴性菌的活性。     

磁性壳聚糖-聚丙烯酸微球固载BSA研究

以牛血清白蛋白(BSA)为模拟蛋白药物,以吸附的方法就磁性壳聚糖-聚丙烯酸微球对BSA的固载效果进行探讨,研究了制备条件(丙烯酸浓度、交联时间、交联剂用量、搅拌速度)和环境因素(溶液的pH、离子强度E、温度T、BSA初始浓度)对其固载效果的影响,并对吸附动力学进行了讨论。结果表明,合成的最佳条件为20%的丙烯酸(AA)10mL、25%戊二醛4mL、交联时间30min、低搅拌速度(r<1000r/min)。磁性壳聚糖-聚丙烯酸微球在固载BSA的过程中受到环境因素(溶液的pH、离子强度E、温度T、BSA初始浓度)的影响,在pH=4.6的磷酸缓冲液中,T=37℃条件下磁性壳聚糖-聚丙烯酸微球对BSA的固载量较大,可达到400mg/g。     

淫羊藿苷壳聚糖/明胶微球的制备及其体外释放研究

本试验以壳聚糖、明胶为载药基质,以中药淫羊藿苷为模拟药物,通过乳化交联的方法制备淫羊藿苷/壳聚糖/明胶微球。考察微球的理化特性,建立持续流动释放系统,检测了微球的体外释放特性和影响因素。微球的理化特性受工艺条件如搅拌速度、乳化剂用量、交联剂用量等因素影响。微球的体外释放速率与微球的粒径、交联度负相关,与载药量正相关。试验结果表明,壳聚糖、明胶可作为缓释微球的载体基质,微球制备工艺简单稳定,微球的释放速率可控,淫羊藿苷/壳聚糖/明胶微球是一种良好的药物释放体系。     

磁性微球与牛血清白蛋白的相互作用

以纳米级四氧化三铁为磁性载体,以苯乙烯为单体,用微悬浮聚合法制备了聚苯乙烯磁性微球;以牛血清白蛋白(BSA)为模型蛋白,用荧光光谱仪和紫外-可见吸收光谱仪研究了磁性微球与BSA的相互作用.结果表明,磁性微球与BSA结合反应的猝灭机理为静态猝灭.     

染料配体脲醛树脂-二氧化锆复合微球的制备及对牛血清白蛋白的萃取性能

采用溶胶-凝胶法制备无孔脲醛树脂-二氧化锆复合微球,在碳酸盐缓冲溶液中,利用微球表面的酰胺键与三嗪染料-活性艳蓝X-BR分子中三嗪环上的活泼氯反应,将染料键合到微球表面,以牛血清白蛋白(BSA)为样品,考察了不同条件下,该萃取剂对BSA的萃取能力。结果表明,该萃取剂对BSA的饱和萃取量达到30.3 mg.g-1,同时萃取的蛋白易于洗脱,1.0 mol.L-1氰化钾的洗脱率达到93.5%。     

聚羟基丁酸酯缓释微球的制备与性能

用溶剂蒸发法制备了以新型生物可降解材料聚羟基丁酸酯为载体、以安定为模药的缓释微球,讨论了药物与载体之比对药物含量与包封率的影响,以及制备微球条件对药物释放性能的影响;微球平均粒径为30～40 μm,粒径分布在 1～1.5之间,最大载药量为19.51%;最高包封率为67.11%;体外累积释放曲线呈"两相"释放特征并拌随初始的"突释效应".扫描电镜观察微球表面呈皱缩表观形态结构,微球内部横断面具有孔道与孔洞,在4℃与室温(20～25 ℃)条件下密封,避光环境下性质稳定.     

阻抗蛋白质吸附载体微球的制备与性能研究

聚合条件对制备功能化微球起到至关重要的作用。在本文中,通过功能单体、烯丙基聚氧乙烯醚(APEG)和苯乙烯的分散共聚制备了一种阻抗蛋白质吸附的功能化微球;然后,通过红外光谱(FT-IR)、动态光散射(DLS)和扫描电镜(SEM)等手段分析这些功能微球的粒径、表面形态和性能;最后通过牛血清蛋白(BSA)吸附实验评价其阻抗吸附性能。实验结果表明：APEG兼具功能单体和稳定剂的功能,在合适的条件下,可以得到良好单分散性的微球。此外,每克聚(苯乙烯-烯丙基聚氧乙烯醚)(P(St-co-APEG))微球的BSA吸附量为0.66 mg,而每克聚(苯乙烯-甲基丙烯酸缩水甘油酯)(P(St-co-GMA))微球的BSA吸附量为4.8 mg。总之,通过分散共聚制备了一种阻抗蛋白质吸附的微球。     

Size ratio effects on interparticle interactions and phase behavior of microsphere-nanoparticle mixtures

We investigate the interparticle interactions and phase behavior of microsphere-nanoparticle mixtures of high charge asymmetry and varying size ratio. In the absence of nanoparticles, negligibly charged microspheres flocculate as a result of van der Waals interactions. Upon addition of a lower critical nanoparticle volume fraction, the microspheres are stabilized by the formation of nanoparticle halos around each microsphere. , A weak attraction between the two species leads to a pronounced enhancement of the effective nanoparticle concentration near the microsphere surface relative to the bulk solution. Above an upper critical nanoparticle volume fraction, the microspheres undergo reentrant gelation. Binary mixtures, in which the effective nanoparticle size is reduced at a fixed microsphere diameter, exhibit a narrow window of stability that ultimately disappears with increasing ionic strength. By contrast, binary mixtures of varying microsphere diameter are stabilized at similar nanoparticle volume fractions and exhibit a broader window of stability with decreasing size ratio. This unexpected observation may arise from the reduced attraction between smaller microspheres because negligible differences in nanoparticle halo formation are observed in these mixtures.     

简易模板剂法制备多级介孔TiO2微球及其在染料敏化太阳能电池中的性能

采用模板剂法一步合成分级结构的介孔TiO₂微球, 考察了烷基胺类模板剂中烷基链长度对介孔TiO₂微球合成及性能影响. 将其应用于染料敏化太阳能电池的光阳极半导体薄膜中, 得到了9.5%-10.1%的高能量转换效率. X射线衍射(XRD)、物理吸附仪(BET)、扫描电镜(SEM)等的分析结果表明: 分级结构介孔TiO₂微球的晶相为纯锐钛矿型; 介孔TiO₂微球表面粗糙, 的纳米粒子堆积形成, 使微球具有介孔性质和较适宜的比表面积. 介孔TiO₂微球堆积形成了利于物质扩散的通道并具有良好的光散射效果; 同时微球介孔粗糙表面保证了染料的大量吸附, 从而提高了电池的光电流. 通过电化学阻抗分析结果验证了分等级结构介孔TiO₂微球光阳极有利于电解液的传输和物质扩散的优异性能.     

Fabrication of polymer microsphere particle standards containing trace explosives using an oil/water emulsion solvent extraction piezoelectric printing process

We present a methodology for fabricating polymer microspheres using inkjet printing of a biodegradable polymer containing either high explosives or high explosive simulant. Poly(dl-lactide/glycolide) 85:15 (PLGA) microsphere production is based on an oil/water emulsion solvent extraction process. The inkjet printing process allows for precise control of the microsphere diameter and the chemical composition. The microspheres can be used as calibrants or verification standards for explosives trace detection instruments. Gas chromatography/mass spectrometry analysis demonstrated that the composition of the microspheres was consistent with predicted concentrations based on the amount of analyte incorporated into the polymer solution and the inkjet operating parameters. We have demonstrated that the microspheres can be fabricated with a mass fraction of 70% of an analyte compound.     

沉淀聚合制备聚(季戊四醇三丙烯酸酯-苯乙烯)单分散微球及其形成机理

以季戊四醇三丙烯酸酯(PETA)作交联剂,苯乙烯作共聚单体,偶氮二异丁腈作引发剂,在乙醇或其与水的混合溶剂中沉淀聚合制备了交联聚合物微球.研究了反应时间、交联剂用量以及溶剂中水含量对聚合过程及微球的影响.结果表明当PETA用量在单体质量的5%-35%之间且反应时间不低于6h时可制得单分散聚合物微球.当PETA用量低于20%时,所得微球的粒径随PETA用量的增加逐渐减小,粒径分布逐渐变窄;此后继续提高PETA用量,微球粒径又逐渐增大,粒径分布逐渐变宽.向反应介质中加入水,可明显提高微球产率及单体转化率,但其体积分数达30%时,所得微球分散性变宽.在此基础上对微球的形成机理也进行了讨论.     

In-Vitro Degradation and Cytotoxicity of Gelatin/Chitosan Microspheres for Drug Controlled Release

The composite microspheres based on gelatin (Gel) and chitosan (Cs) loaded with 5-fluorouracil (5-FU) were fabricated using glutaraldehyde (GA) as a crosslinker. The in-vitro degradation behaviors of the Gel/Cs microspheres, including the changes of pH value, mass loss and microsphere morphology, were studied. The in-vitro cytotoxicites of Gel/Cs microspheres loaded and unloaded with 5-FU were carried out with MCF-7 breast cancer cell line. The empty Gel/Cs microspheres showed a smooth surface and were evenly distributed; however, there was much aggregation observed for the microspheres loaded with 5-FU. The degradation results showed that the pH values of both PBS and PBS-lysozyme solutions increased with increasing degradation time but the increase of pH value of PBS-lysozyme solution was quicker than that of PBS solution. The aggregated Gel/Cs microspheres lose their shape and many fibers were found after 21 days in PBS solution; while the Gel/Cs microsphere disappeared in PBS-lysozyme solution. The mass loss of the Gel/Cs microspheres in PBS-lysozyme solution was larger than that of the Gel/Cs in PBS solution. The results indicated that lysozyme can accelerate the degradation of Gel/Cs microspheres. The cytotoxicity results showed that the cell viability decreased with increasing glutaraldehyde content for the empty Gel/Cs microspheres; however, the cell viability increased with increasing glutaraldehyde content for the Gel/Cs microspheres loaded with 5-FU. Therefore, the Gel/Cs microspheres can be offered as drug carrier candidates for long-term applications of anti-cancer drugs.     

Spray dried calcium gelled arabinoxylan microspheres: A novel carrier for extended drug delivery

Arabinoxylan (AX) microspheres were formulated by ionotropic gelation for extended drug delivery. AX from Plantago ovata was tested for gelation with aluminium, barium, calcium, magnesium, and iron(III) chloride. Only calcium was found to lead to weak gelation with AX. The conventional needle extrusion produced fragile AX beads with calcium and hence the spray drying process was adopted for the preparation of metronidazole hydrochloride (MH) loaded AX microspheres. MH loading in AX microspheres was 30.8 mass %, 31.9 mass %, and 29.3 mass % in formulations gelled with 0.05 g, 0.1 g, and 0.15 g of calcium chloride per 100 mL of solution, respectively. Scanning electron microscopy revealed the crystallinity reduction of MH in microspheres. The surface of drug loaded calcium gelled AX microsphere was rougher than that of an ungelled one. Interactions of calcium with AX and the amorphous nature of the drug in the microspheres were evidenced by infrared spectroscopy and X-ray diffraction studies. Calcium-induced gelation can extend the drug release to over 90 min in 0.1 M HCl despite the hydrophilic nature of AX and the high solubility of metronidazole.     

高压静电法制备多孔磁性壳聚糖微球

以壳聚糖(Chitosan, CS)为基质, 通过共混法引入四氧化三铁磁性颗粒, 以硅胶(Silicagel, S)为致孔剂, 在热的NaOH溶液中溶出硅胶致孔, 采用高压静电法制备磁性壳聚糖微球. 通过SEM观察了微球的结构和形貌, 并对微球结构和形貌的影响因素及其制备工艺进行了系统的研究, 结果表明, 高压静电法制备的磁性硅胶/壳聚糖微球粒径可通过微量进样器的针头大小来控制, 并且粒径分布均匀, 实验重复性及可控性好; 当以质量体积分数为5%的壳聚糖醋酸溶液(体积分数2％, mS∶mCS=4∶1), 用8号针头进样时, 制得直径约为600 μm, 孔洞分布均匀, 孔径约为50 μm的多孔磁性壳聚糖微球. 由于磁性多孔壳聚糖微球中含有大量的活性羟基和氨基, 因此显弱碱性, 对酸性物质和金属离子的吸附作用很好, 且可通过外加磁场进行有效分离. 磁性多孔壳聚糖微球在生物分离及污水中的酸性染料处理方面具有潜在的应用价值.     

131I标记海藻酸钠包裹明胶微球的制备及性能评价

建立了明胶微球和海藻酸钠(SA)包裹微球的制备方法,并通过实验比较了明胶微球和包裹微球的各种特性,最后用氯胺T法将125I及131I分别标记在微球上.结果表明,包裹微球对碘有更高的负载量和稳定性;在相同条件下,包裹微球的降解时间比明胶微球的降解时间长;将标记后的明胶微球通过直接注射介入到新西兰大白兔的肝脏,采用发射单光...     

Synthesis and characterization of heat-stabilized albumin magnetic microspheres

Human serum albumin magnetic microspheres containing 30% iron oxide particles were synthesized by a heat-stabilization process. The average diameter, the size distribution and the morphology were characterized by scanning electron microscopy, atomic force microscopy and transmission electron microscopy. The distribution of the iron oxide nanoparticles within the microspheres was confirmed by the contrast obtained in the morphology by backscattered electron imaging in scanning electron microscopy. Energy-dispersive X-ray spectroscopy showed the presence of iron in the microspheres. The cabbage like surface structure in some of the microspheres obtained in scanning electron microscopy can be better understood by atomic force microscopy. This peculiar surface structure in the microsphere may be due to the cross-linking in the protein molecule by heat. The amount of iron oxide in the microsphere was analyzed by atomic absorption spectroscopy. The magnetic properties of the particles were measured in a superconducting quantum interference device magnetometer. Received: 12 September 2000 Accepted: 5 February 2001