包埋载药微球的羟基磷灰石/聚氨酯复合组织工程支架的研究

研制具有药物缓释功能的骨组织工程支架, 对载药微球包埋于羟基磷灰石/聚氨酯(HA/PU)支架中的药物缓释体系进行了可行性研究. 首先将盐酸环丙沙星作为模型药物, 包裹于乙基纤维素(EC)微球中, 然后将EC微球与HA/PU材料进行复合, 制备了抗生素药物缓释支架. 结果显示EC微球均匀地分布在HA/PU支架基质中, 未对支架的开孔结构和孔隙形貌构成影响. 与单纯将药物载入HA/PU支架中相比, 复合载药EC微球的HA/PU支架的初期药物暴释明显降低, 药物缓释时间延长. 体外药物释放实验和抑菌实验结果表明, 该载药微球支架具有良好的药物缓释功能和抑菌性能, 是一种集骨修复和治疗于一体的新型组织工程支架材料.     

纳米羟基磷灰石/聚氨酯载药微球的制备及性能

通过乳液聚合法制备了负载阿莫西林的纳米羟基磷灰石/聚氨酯(n-HA/PU)载药微球,通过正交设计实验对其制备工艺进行了优化,采用红外光谱、热重分析、扫描电镜等分析了微球的结构和性能,对其体外药物缓释过程进行探讨。研究结果表明,复合微球粒径大小与固含量、聚乙烯吡咯烷酮(PVP)含量、搅拌速度等有关,所制备的微球平均粒径为0.8~1.2mm;载药微球的优化制备工艺条件为:原料配比-NCO∶-OH=2∶1,预聚时间180min,预聚温度80℃,nHA含量3%,固含量7%,搅拌速度600r/min,PVP用量3%,所制备微球的载药量为6.58%,包封率为86.86%。体外缓释结果表明,载药微球的释药行为符合Higuchi动力学,半衰期(t1/2)为22.29h,具有良好的药物缓释作用。     

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.     

原位纳米羟基磷灰石/壳聚糖复合载药微球的制备及释放性能研究

为应对骨缺损修复过程中的细菌感染问题,利用原位法制备了具有药物缓释功能的纳米羟基磷灰石(n-HA)和壳聚糖(CS)复合微球,并与纯CS载药微球和共混法n-HA/CS复合载药微球进行对比研究。利用相差显微镜和扫描电镜对微球进行形貌观察,结果显示原位法复合载药微球表面形态和球形度均较好。对载药微球的载药率、药物包封率和体外药物释放进行了测试和分析,结果表明原位法复合载药微球载药率和药物包封率最高,分别为(0.3907±0.0203)%和(7.4221±0.3858)%,并具有明显的缓释效果。     

壳聚糖靶向缓释功能高分子载药微球及其特性研究

采用壳聚糖作为载体,通过分子结构设计,以叶酸靶向受体改性壳聚糖,然后选择5-氟尿嘧啶为模型药物,采用复凝聚法制备新型壳聚糖靶向缓释功能高分子载药微球。通过红外光谱和1 H-NMR核磁共振分析确定了叶酸改性壳聚糖化学结构,并通过扫描电镜、激光粒度分析仪、激光共聚焦显微镜及紫外光谱等现代仪器和分析方法对载药微球的形貌结构、粒径、包埋率、载药量和体外药物释放特性等进行研究。结果表明,模型药物被成功包埋到叶酸改性后的壳聚糖微球中,包埋率E和载药量L最高可达86.5%和32.7%,载药微球的平均粒径为5.251μm,多分散系数(PDI)为0.056,球形度、分散性良好;激光共聚焦显微镜结果显示微球为核壳结构;体外释放实验表明壳聚糖靶向缓释功能高分子载药微球具有持久的缓释作用,24h后载药微球在模拟胃液(pH值=1.2)中释放率为70%,在模拟肠液(pH值=7.4)中释放率为40%,释药速度与释放介质的pH值密切相关。     

BSA-PLGA微球的优化制备及特性

目的:优化BSA-PLGA微球制备工艺,并对其包封率、形态、体外释放药物及微球包裹前后BSA的稳定性进行评价。方法:以PLGA为载体,采用复乳溶剂挥发法制备BSA-PLGA微球。Micro BCA法测定微球的包封率和载药量,扫描电子显微镜观察微球的形态,激光粒度仪测定粒度及分布,聚丙烯酰胺凝胶电泳(SDS-PAGE)研究微球包裹前后BSA分子结构的完整性,同时考察体外释药性能。结果:根据优化工艺制备的微球外观圆整,平均粒径(2275.8±256.9)nm,包封率(82.59±2.92)%,载药量(13.76±0.49)×10-2%,包裹前后BSA结构稳定,体外释放28天以上,释放曲线符合Higuchi方程。结论:本研究获得了较优化的BSA-PLGA微球制备工艺,所制备的微球具有较高的包封率和明显的缓释效果。     

聚乳酸微球制备工艺优化的研究

以丙酸睾丸素为囊心物制备聚乳酸微球,使用L16(4^5)正交实验表考察了不同因素对粒径,收率和包结率的影响,经统计学处理得到制备注射用缓释微球的最佳工艺条件,并考察了此条件的重现性,微球的体外释药实验表明微球可维持缓释达三个月。     

抗菌活性微球与PVA静电纺复合纤维膜的构建与其长效缓释性能研究

姜科药物姜黄素具有消毒杀菌、抗炎抗癌等多重医药作用，是理想的天然药物材料，但是其稳定性较差，吸收率较低，在人体中代谢较快，导致其生物利用度较低。通过反向乳液聚合制备了壳聚糖/姜黄素微球，并利用静电纺丝技术将其与聚乙烯醇(PVA)混纺制备成壳聚糖/姜黄素微球与PVA共混纤维膜。通过红外光谱和扫描电镜(SEM)对得到的纳米纤维膜进行性能表征，并通过调控微球与PVA比例提高纳米纤维膜的力学性能、缓释性能以及抑菌率。结果表明：当微球与PVA质量比为1∶5时，共混纤维膜机械性能最佳；药物累计释放测试结果表明，体外释放时长可达54h,缓释曲线符合Ritger-Peppas模型；抗菌测试结果表明，对于金黄色葡萄球菌，载药纤维膜的抑菌率可达99.9%。     

超声改性淀粉/PVA/SA复合微球的制备及性能研究

用凝聚相分离法制备超声改性淀粉/聚乙烯醇/海藻酸钠(ST/PVA/SA)复合微球,考察了ST、PVA、SA和CaCl2的质量分数、干燥方式对微球形态性能的影响。通过红外光谱对微球进行了结构表征,并测定了微球的含水率、溶胀率、降解率。研究了载药微球在体外的药物释放规律。结果表明,微球的最佳合成条件是ST、PVA、SA和CaCl2的质量分数分别为4%、8%、4%和5%,此条件下微球具有良好的pH敏感性和药物缓释效果。     

碳酸钙纳米结构多孔空心微球的制备及其药物缓释性能研究

以CaCl2和Na2CO3为反应物,十二烷基硫酸钠(SDS)为表面活性剂,在室温水溶液中制备了纳米结构碳酸钙空心球.用TEM和SEM对其进行形貌观察发现,所制备的碳酸钙空心球的球壁由纳米粒子组成,具有多孔形貌特征.分别在模拟胃液(pH＝1.2)以及模拟肠液(pH＝7.4)中对制备的纳米结构碳酸钙空心球进行了药物装载和缓释性能的研究,选用的药物为布洛芬(IBU).研究结果表明,IBU/CaCO3多孔空心微球药物传输体系具有较高的药物装载量和良好的药物缓释性能,纳米结构碳酸钙空心球中IBU的装载量可以达到195mg/g,且连续释药时间能持续53h以上;除去表面活性剂后,载体中IBU的装载量可达到130mg/g,药物释放率为100%时,持续释药时间可达到40h.纳米结构碳酸钙多孔空心球作为药物载体材料在药物缓释体系中具有潜在的应用前景.     

Preparation and property of a novel bone graft composite consisting of rhBMP-2 loaded PLGA microspheres and calcium phosphate cement

Calcium phosphate cement (CPC) is a highly promising bone substitute and an excellent carrier for delivering growth factors. Yet, the lack of macro-porosity and osteoinductive ability, limit its use. This study is aimed at developing a novel biodegradable biomaterial for bone repair with both highly osteoconductive and osteoinductive properties. RhBMP-2 loaded PLGA microspheres were incorporated into rhBMP-2/CPC for macropores for bone ingrowth. The compressive strength, crystallinity, microscopic structure, and bioactivity of the composites were investigated. The results showed that with the incorporation of rhBMP-2 loaded PLGA microspheres, the compressive strength was decreased from (29.48 ± 6.42) MPa to (8.26 ± 3.58) MPa. X-ray diffraction revealed that the crystallinity pattern of HA formed by CPC had no significant change. Inside the composite, the microspheres distributed homogeneously and contacted intimately with the HA matrix, as observed by scanning electron microscopy (SEM). When the PLGA microspheres dissolved after having been emerged in PBS for 56 days, macropores were created within the CPC. The rhBMP-2/PLGA/CPC composite, showing a 4.9% initial release of rhBMP-2 in 24 h, followed by a prolonged release for 28 days, should have a greater amount of rhBMP-2 released compared to the CPC delivery system. When rabbit marrow stromal cells were cocultured with the composite, the alkaline phosphatase (ALP) and osteocalcin (OC) showed a dose response to the rhBMP-2 released from the composite, indicating that the activity of rhBMP-2 was retained. This study shows that the new composite reveals more rhBMP-2 release and osteogenic activity. This novel BMP/PLGA/CPC composite could be a promising synthetic bone graft in craniofacial and orthopedic repairs.     

Composite chitosan and calcium sulfate scaffold for dual delivery of vancomycin and recombinant human bone morphogenetic protein-2

A biodegradable, composite bone graft, composed of chitosan microspheres embedded in calcium sulfate, was evaluated in vitro for point-of-care loading and delivery of antibiotics and growth factors to prevent infection and stimulate healing in large bone injuries. Microspheres were loaded with rhBMP-2 or vancomycin prior to mixing into calcium sulfate loaded with vancomycin. Composites were evaluated for set time, drug release kinetics, and bacteriostatic/bactericidal activity of released vancomycin, induction of ALP expression by released rhBMP-2, and interaction of drugs on cells. Results showed the composite set in under 36 min and released vancomycin levels that were bactericidal to S. aureus (>MIC 8–16 μg/mL) for 18 days. Composites exhibited a 1 day-delayed release, followed by a continuous release of rhBMP-2 over 6 weeks; ranging from 0.06 to 1.49 ng/mL, and showed a dose dependent release based on initial loading. Released rhBMP-2 levels were, however, too low to induce detectable levels of ALP in W20-17 cells, due to the affinity of rhBMP-2 for calcium-based materials. With stimulating amounts of rhBMP-2 (>50 ng/mL), the ALP response from W-20-17 cells was inhibited when exposed to high vancomycin levels (1,800–3,600 μg/mL). This dual-delivery system is an attractive alternative to single delivery or preloaded systems for bone regeneration since it can simultaneously fight infection and deliver a potent growth factor. Additionally, this composite can accommodate a wide range of therapeutics and thus be customizable for specific patient needs, however, the potential interactive effects of multiple agents must be investigated to ensure that functional activity is not altered.     

Effects of porous beta-tricalcium phosphate-based ceramics used as an E. coli-derived rhBMP-2 carrier for bone regeneration

Recombinant human bone morphogenetic protein-2 (rhBMP-2) requires carriers for clinical effectiveness. In this study, whether porous beta-tricalcium phosphate (β-TCP)-based ceramics are ideal carriers for rhBMP-2 was investigated. Hydroxyapatite (HA), β-TCP, TCP/HA (80 %/20 %), HA with rhBMP-2, TCP with rhBMP-2, and TCP/HA (80 %/20 %) with rhBMP-2 were manufactured by a sponge method with a pore size of 300 μm or more and macro-porosity of 83 %. The alkaline phosphatase (ALP) activity and ALP expression of the cells with 100 % β-TCP granules were more increased than the those of cells with 100 % HA and TCP/HA (80 %/20 %) at the baseline or when treated with 15 ng/ml of rhBMP-2. In an SD rat calvarial defect model, new bone formation was evidently shown in the TCP 100 %-rhBMP-2 and TCP/HA (80 %/20 %)-rhBMP-2 groups, showing that the most affected area was filled with newly-formed bone, that the percent bone volume and trabecular number were larger when compared to the groups without rhBMP-2 treatment at both 4 and 8 weeks after surgery using micro-CT and histology. Porous TCP-based ceramic granules enhanced the osteoblastic differentiation in the hMSC system when treated with 15 ng/ml of rhBMP-2 and accelerated bone-healing by trabecular number in a rat calvarial defect model. Thus, in this study it was proposed that TCP-based ceramics might be useful carriers of rhBMP-2.     

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。     

Gd_2O_3空心微球的制备及Gd_2O_3/丁基橡胶复合材料低频阻尼性能

以分散聚合法制备的聚苯乙烯(PS)微球作为模板,通过均相沉淀法制备前驱体PS-Gd(OH)CO_3复合微球,高温煅烧后得到Gd_2O_3空心微球,将其与丁基橡胶复合制备低频高阻尼Gd_2O_3/丁基橡胶复合材料。采用FTIR、SEM、TEM分析、TG分析仪、XRD分析和XPS对Gd_2O_3空心微球的形貌与结构组成进行表征。将Gd_2O_3空心微球与粉体分别作为填料加入丁基橡胶中制备Gd_2O_3/丁基橡胶复合材料。结果表明:Gd_2O_3空心微球由立方萤石结构的颗粒组成,外空心直径为0.9μm,壳层厚度约为100nm;添加空心微球的复合材料阻尼性能较好;与纯丁基橡胶相比,Gd_2O_3/丁基橡胶复合材料的低频阻尼性能明显提高。     

铕掺杂的TiO2空心微球的制备及光催化性能

通过溶胶-凝胶法制备未掺杂和铕掺杂的TiO₂空心微球, 采用XRD、SEM、TEM、HRTEM、BET和XPS等技术对样品进行表征, 以亚甲基蓝的光催化降解为目标反应, 评价其光催化活性。结果表明, 钛酸四丁酯(TBOT)的加入量对微球的形貌影响较大, 当滴加1.5 mL的TBOT时, 可得结构清晰、分散性良好的TiO₂空心微球。XRD分析表明, 400℃煅烧的纳米TiO₂空心微球为锐钛矿, 掺铕可抑制TiO₂的晶相转变。光催化实验表明, 铕掺杂能显著提高TiO₂空心微球的活性。当铕掺量为0.7%时, 所得样品粒径和孔径最小, 比表面积最大, 光催化活性最高。     

TiO2-ZnO复合中空微球的制备及光催化性能

以Ti（SO₄）₂和Zn（NO₃）₂为原料,采用水热法制备TiO₂-ZnO复合中空微球光催化剂。通过FTIR、XRD、SEM、紫外可见漫反射光谱（UV-Vis DRS）、XPS及N₂吸附-脱附等方法对TiO₂-ZnO复合光催化剂的结构和性能进行表征,并以亚甲基蓝（MB）为目标降解物,评价TiO₂-ZnO复合中空微球光催化活性。结果表明,TiO₂-ZnO光催化剂具有中空微球结构,粒径为1~2 μm,比表面积为30.46 m2/g。TiO₂的加入可提高ZnO对光的吸收,有效降低电子空穴复合率。在高压Hg灯照射下,TiO₂-ZnO复合中空微球的光催化性能均高于纯ZnO,其中Zn（NO₃）₂与Ti（SO₄）₂摩尔比为1:0.7条件下制备的TiO₂-ZnO复合中空微球样品表现出较好的光催化活性,光照60 min,对MB的降解率可达95.8%,其光催化降解速率是纯ZnO的4.3倍。      

中空TiO2微球的制备及其对聚丙烯酸酯薄膜保温性能的影响

以阳离子PS微球为模板, 钛酸四丁酯为钛源, 氨水为催化剂制备中空TiO₂微球, 通过物理共混法将中空TiO₂微球引入到聚丙烯酸酯薄膜中, 考察了中空TiO₂微球的空心粒径及用量对复合薄膜光反射性、导热系数及力学性能的影响。结果表明: 中空TiO₂微球的引入可显著提升聚丙烯酸酯薄膜的各项性能, 中空TiO₂微球的空心粒径和用量对复合薄膜的性能有不同程度的影响, 随着中空TiO₂微球空心粒径和用量的增加, 复合薄膜的性能基本呈现先提升后降低的趋势, 其中当中空TiO₂微球空心粒径为300 nm、用量为1%时, 所制备的复合薄膜保温性能和力学性能最优。     

Injectable thermogelling chitosan for the local delivery of bone morphogenetic protein

The aim of the present study was to evaluate the in vivo biocompatibility of injectable thermo gelling chitosan-ammonium hydrogen phosphate solution (chitosan-AHP) and its efficacy to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in a bioactive form. The thermogel showed a typical foreign body response upon subcutaneous implantation surrounded by a fibrous capsule. Even at 4 and 8?weeks post implantation, significant neutrophil infiltration was observed within the gel. Chitosan-AHP gel retained most of the loaded rhBMP-2 after a small initial release. The bioactivity of the released protein was demonstrated in vitro by the increase in alkaline phosphatase activity of mouse pre osteoblast cells (MC3T3-E1). Histological and micro-computed tomography (μCT) evaluation showed evidence of ectopic bone formation upon 4?μg/mL rhBMP-2 loaded chitosan-AHP injection. The study demonstrated a neutrophil mediated local tissue response to chitosan-AHP gel and its ability to encapsulate and maintain the bioactivity of rhBMP-2.     

中空SiO2微球的制备及其在缓/控释应用中的新进展

中空二氧化硅(SiO₂)微球具有特殊的内部空腔、吸附渗透性好、物质传递可控等优异性能, 可储存负载并缓慢释放药物、香精、染料、菌素等客体分子, 因此在药物缓释、医学成像、环境保护以及化妆品等领域有着广阔的应用前景。根据国内外研究进展, 本文归纳对比了中空SiO₂微球几种制备方法之间的优劣差异, 着重阐述了其作为缓控释载体表现出的持久性和高效性, 以及功能化的有机/无机杂化微球在响应性控释方面的优越性。并对中空SiO₂微球作为新型缓控释载体的发展前景进行了展望。