Preparation,characterization, in vitro bioactivity and protein loading/release property of mesoporous bioactive glass microspheres with different compositions

Mesoporous bioactive glass microspheres (MBGMs) with large mesopores have attracted considerable attention in the field of bone tissue regeneration and drug delivery systems due to their excellent bioactivity, biocompatibility and high specific area. In this study, a loose structure of MBGMs with adjustable chemical compositions was synthesized by the combination of sol-gel and water-in-oil (W/O) microemulsion. All the prepared MBGMs possessed a large mesopore diameter that increased with CaO content, a high surface area and good apatite-inducing formation ability. In vitro protein absorption and release assays demonstrated that the MBGMs exhibited decreased loading efficiency and burst release behavior as the CaO content increased. Additionally, an enhanced BSA-loading amount and prolonged release curve were obtained after the surfaces of MBGMs were modified by amine groups. Furthermore, the preliminary in vitro cell experiments showed that MBGMs exhibited good biocompatibility. The results indicated that MBGMs could be a promising candidate as a drug/protein carrier for bone tissue regeneration.     

Preparation and characterization of collagen microspheres for sustained release of VEGF

In this study, we prepared injectable collagen microspheres for the sustained delivery of recombinant human vascular endothelial growth factor (rhVEGF) for tissue engineering. Collagen solution was formed into microspheres under a water-in-oil emulsion condition, followed by crosslinking with water-soluble carbodiimide. Various sizes of collagen microspheres in the range of 1–30 μm diameters could be obtained by controlling the surfactant concentration and rotating speed of the emulsified mixture. Particle size proportionally decreased with increasing the rotating speed (1.8 μm per 100 rpm increase in the range of 300–1,200 rpm) and surfactant concentration (3.1 μm per 0.1% increase in the range of 0.1–0.5%). The collagen microspheres showed a slight positive charge of 8.86 and 3.15 mV in phosphate-buffered saline and culture medium, respectively. Release study showed the sustained release of rhVEGF for 4 weeks. Released rhVEGF was able to induce capillary formation of human umbilical vein endothelial cells, indicating the maintenance of rhVEGF bioactivity after release. In conclusion, the results suggest that the collagen microspheres have potential for sustained release of rhVEGF.     

乙烯基胶原蛋白微球的制备及其应用

为了得到带有"-C=C-"的胶原蛋白微球,我们使用甲基丙烯酸酐对胶原蛋白改性,再采用乳化交联法将改性胶原蛋白制备成乙烯基胶原蛋白微球(CMAs),并将微球应用到尼龙基材上.研究了CMAs的制备条件,使用傅里叶红外光谱(FT-IR)、扫描电子显微镜(SEM)、激光粒度分析仪等对CMAs和乙烯基胶原蛋白微球/尼龙(Nylo...     

Synthesis and in vitro bioactivity of novel mesoporous hollow bioactive glass microspheres

The remarkable tissue-repairing bioactivity and biocompatibility of bioactive glass make it suitable for a wide range of applications. Here, novel mesoporous hollow bioactive glass microspheres (MHBGMs) with a uniform diameter range of 2-5 µm were prepared by a sol-gel method. Structural characterization indicated that the shell of hollow sphere had a mesopore size range between 2 and 10 nm and a thickness about 500 nm. The in vitro bioactivity test indicated that the novel structure exhibited high in vitro bioactivity. The uniform microspherical morphology and mesoporous hollow structure of MHBGMs, together with their high bioactivity, turn them into a good candidate as an injectable and drug-loading biomaterial for in vivo tissue regeneration and drug control release.     

二氧化钛空心微球的制备及表征

采用模板法制备了可控制球壳厚度的亚微米二氧化钛空心微球.首先利用钛酸四丁酯乙醇溶液和聚苯乙烯粒子制备了二氧化钛/聚苯乙烯复合粒子,在空气中经500℃煅烧除去苯乙烯模板后得到锐钛矿二氧化钛空心微球.透射电镜和扫描电镜观察表明,二氧化钛/聚苯乙烯复合粒子煅烧后体积发生了急剧的收缩,形成具有空心结构二氧化钛微球.电子衍射和X射线衍射分析可知空心微球的二氧化钛球壳为锐钛矿.实验发现当钛酸四丁酯与乙醇的体积比从120提高到110时,二氧化钛空心微球的球壳厚度从20～25 nm增加到45～50nm;以不同粒径的聚苯乙烯粒子作模板,可以得到不同内孔直径的二氧化钛空心微球,其内孔直径比聚苯乙烯模板直径小15%～20%.     

磁性聚乙烯醇缩丁醛微球的制备和性质

运用乳化复合技术制备出磁性聚乙烯醇缩丁醛微球。该微球呈珠状 ,平均粒径为10～ 2 0nm ,具有较大的蛋白质固载量 ,可作为载体对多种酶及蛋白质加以固定。并研究了磁性聚乙烯醇缩丁醛微球制备条件、吸附时间、pH值等对磁性聚乙烯醇缩丁醛微球固定蛋白载量的影响     

Preparation and characterization of protein-loaded polyanhydride microspheres

Poly(1,3-bis-(p-carboxyphenoxy propane)-co-(sebacic anhydride) (P(CPP-SA)) have the anhydride bonds in copolymer backbone, which are available for degradation on the base of passive hydrolysis. This chemical structure made it degraded within a short time in linear degradation rate. For this property, polyanhydrides are one of the most suitable biodegradable polymers employed as drug carriers. This paper aimed at researching the erosion and degradation of P(CPP-SA) microspheres with CPP/SA monomer ratios of 20:80, 35:65 and 50:50. In vitro protein release from the microspheres was also investigated in this paper. Human serum albumin (HSA) was used as the model protein. In this research, the microspheres degradation and drug release rate from microspheres can be adjusted by altering the CPP/SA ratios of P(CPP-SA). The features of surface erosion were observed in SEM. The structural integrity of HSA extracted from microspheres was detected by gel permeation chromatography, compared with native HSA. The results showed HSA remained its molecule weight after encapsulated.     

Preparation and characterization of ketoprofen-loaded microspheres for embolization

To deliver drug locally and relieve the syndrome of pain after uterine artery embolization, N-[tris (hydroxymethyl) methyl] acrylamide-gelatin microspheres were prepared based on inverse suspension polymerization and then separated into a number of subgroups (150–350, 350–560, 560–710, 710–1,000, and 1,000–1,430 μm) by wet-sieving. The microspheres were dried by lyophilization or by washing with anhydrous ethanol. And ketoprofen was loaded by soaking dried blank microspheres into concentrated ketoprofen ethanol solution. The ketoprofen loading level in different subgroups of microspheres was measured and found higher when the microspheres were dried by lyophilization. Equilibrium water content and mean diameters of microspheres decreased after drug loading, especially in subgroups with larger size. The microspheres went through the catheter without any difficulty. Compression and relaxation tests were performed on microspheres before lyophilization, embosphere™, microspheres after lyophilization and ketoprofen loading microspheres. The Young’s moduli were 54.74, 64.19, 98.15, and 120.44 kPa, respectively. The release of ketoprofen from microspheres in different subgroups was studied by using the USPII method and T-cell apparatus, respectively. The results indicate that the release rate of ketoprofen depends upon the diameter of microspheres, the type of dissolution apparatus and the flow rate of media in the case that T-cell apparatus was applied. The CH50 test shows that the activation of complement by ketoprofen-loaded microspheres was lower than by blank ones.     

聚乳酸头孢唑啉钠微球的制备及其性能表征

采用复乳法制备聚乳酸．头孢唑啉钠（PLA-CEZ）微球．扫描电子显微镜（SEM）和差热分析（DTA）结果表明，PLA-CEZ呈现完整的球形且聚乳酸和模型药物能够有机地结合为一体．同时，探讨了聚乳酸分子量大小及释药介质对载药微球释放速度的影响；释药曲线显示，PLA-CEZ微球具有很好的缓释效果．     

Preparation and characterization of chitosan microspheres containing doxifluridine

Chitosan microspheres containing 5-fluorouracil (5-FU), tegafur (FT), and doxifluridine (DFUR) were prepared by the dry-in-oil method using silicone oil with no surfactant as a dispersion medium. For DFUR-containing chitosan microspheres (DFUR-M), reacetylation with acetic anhydride or coating using chitosan and glutaraldehyde was performed. DFUR-M, reacetylated DFUR-M, and chitosan-coated DFUR-M were investigated on in vitro drug release, and the former two microspheres were examined for in vivo degradation after subcutaneous (s.c.) implantation in mice, and in vivo plasma concentration-time profiles after s.c. implantation in rats. The present method gave fairly large microspheres purely composed of chitosan and drug because of no use of surfactant, which showed the mean particle diameters of 300-900 µm and the drug contents of 4-22% (w/w). Encapsulation efficiency of DFUR was higher than that of 5-FU and FT. DFUR-M and reacetylated DFUR-M exhibited spherical shape except chitosan-coated DFUR-M. DFUR-M showed high initial rapid release, which was suppressed to some extent by reacetylation or chitosan coating. DFUR-M and reacetylated DFUR-M subcutaneously implanted were gradually degraded, and approximately half or a little more of the microspheres disappeared from the implanted site at 3 weeks postimplantation. DFUR-M and reacetylated DFUR-M implanted subcutaneously gave similar plasma concentration-time profiles of DFUR, which did not indicate prolonged release in vivo. DFUR-containing chitosan microspheres with fairly large size and good drug content could be obtained by the present preparation but remained to be improved for drug release properties.     

双氯灭痛壳聚糖水凝胶微球的制备及其性能研究

在Span80与植物油形成的反相胶束体系中,通过戊二醛交联制备出壳聚糖水凝胶微球(CHM)。采用红外光谱和透射电镜等方法对CHM结构及粒子形态进行了研究。同时对CHM的溶胀度及其对模型药物双氯灭痛的体外释放行为进行了考察。结果表明,CHM具有较好的控制药物释放的作用。交联程度对微球粒径、溶胀度及药物释放性能影响较大。     

Alkali oxide containing mesoporous bioactive glasses: Synthesis,characterization and in vitro bioactivity

We report, for the first time, the synthesis of sodium oxide containing mesoporous bioactive quaternary glasses and compared with two different mesoporous ternary silicate systems by modified sol–gel process. With the aid of three different glass systems, a systematic analysis has been made on phosphorous-bearing (P-bearing) and phosphorous-free (P-free) mesoporous bioactive glasses to investigate the role of phosphorus on in vitro bioactivity of various silicate glasses with constant alkali oxide content. The combined use of multiple analytical techniques XRD, FTIR, SEM, nitrogen adsorption/desorption analysis before and after soaking in the SBF solution allowed us to establish strong correlation between composition, pore structure and bioactivity. We find that the P-bearing mesoporous glasses show the rapid hydroxycarbonate apatite (HCA) crystallization than P-free mesoporous glasses independent of calcium content. The present study reveals that the presence of phosphorous jointly with calcium in the bioactive glass system significantly enhances the rate of apatite formation as well as crystallization of apatite phase. Additionally, we find that a glass with sodium orthophosphate rich phase enhances the solubility when immersed in SBF and further accelerate the kinetics of apatite formation. The influences of the chemical composition and their superior textural properties on bioactivity are explained in terms of the unique structure of mesoporous bioactive glasses.     

Preparation and characterization of spray-dried mucoadhesive microspheres of aceclofenac

Objective: Microencapsulation of the anti-inflammatory drug aceclofenac (ACE) was investigated as a means of controlling drug release and minimizing or eliminating local side effects. Method: Microspheres were prepared by a spray-drying technique using solutions of ACE and three polymers, namely, carbopol, chitosan, and polycarbophil, in different weight ratios. Results: The spray-dried mucoadhesive microspheres were characterized in terms of shape (scanning electron microscope), size (6.60–8.40 μm), production yield (34.10–55.62%), and encapsulation efficiency (58.14–90.57%). In vitro release studies were performed in phosphate buffer (pH 6.8) up to 10 hours. The spray-drying process of solutions of ACE with polymeric blends can give prolonged drug release. The in vitro release data were well fit into Higuchi and Korsmeyer–Peppas model and followed Fickian diffusion mechanism. In vivo data showed that the administration of ACE in polymeric microspheres prevented the gastric side effects. Conclusion: The formulations here described can be proposed for the oral administration of nonsteroidal anti-inflammatory drugs with minimal side effects on gastric mucosa.     

表面功能化聚苯乙烯磁性微球的制备及表征

以纳米级四氧化三铁(Fe3O4)为磁性载体,以苯乙烯(St)、丙烯酸(AA)和丙烯酸甲酯(MA)为单体,用微悬浮聚合法制备了表面功能化聚苯乙烯磁性微球,并对聚合过程中预处理、温度、Fe3O4/St比、分散剂的影响进行了讨论。扫描电镜照片和磁滞回线显示微球分散性好,具有超顺磁性;热失重-差热分析表明其磁含量高;红外光谱表明微球表面含有羧基基团;通过电导率仪测试,计算出了微球表面羧基含量。结果表明,丙烯酸甲酯改性的羧基磁性微球比丙烯酸改性的性能要好。     

含蒽醌生色团聚合物微球的制备及表征

在二氯甲烷中使丙烯酰氯与1-氨基蒽醌(1-AQ)反应合成了反应性1-丙烯酰胺基蒽醌(N-AQ)黄色染料,采用傅里叶变换红外光谱(FT-IR)和质子核磁共振(1H NMR)对其进行表征,表明制得的N-AQ结构明确。进而通过分散聚合法,使N-AQ与甲基丙烯酸甲酯(MMA)共聚,成功制备了黄色P(MMA-co-N-AQ)聚合物微球。由扫描电子显微镜(SEM)和zeta电位及粒度分析仪对微球的形态、大小及分布进行了表征,并利用可见光-紫外光谱仪(UV-Vis)对微球中引入的N-AQ含量进行了定量分析。结果表明,反应性染料的转化率达93.6%,在聚合反应中改变N-AQ的用量,可将所制备的微球粒径控制在1.3～3μm之间,球形完好、表面光滑、粒径均一,可望应用于彩色激光打印。     

以Al2O3为核心的铜金属微球的制备与表征

基于溶液/氧化铝界面的自催化氧化一还原反应,通过金属铜在氧化铝粉末表面上的化学沉积,制备了以氧化铝为核心的铜金属微球.用X射线衍射分析(XRD)、扫描电子显微术(SEM)和傅立叶变换红外光谱分析(FTIR)综合表征了产品的形貌及结构情况.产品的粒径约为50μm,金属壳层是由纳米级大小的多晶铜颗粒组成.产品的松装密度大约为2.4g@cm-3,导电性类似于金属铜粉.     

Preparation, characterization, and mucoadhesive properties of chitosan-coated microspheres encapsulated with cyclosporine A

The aim of this study was to prepare and characterize chitosan-coated microspheres containing cyclosporine A (CyA). Microspheres encapsulated with CyA were prepared by solvent evaporation-emulsification methods. Microspheres were immersed in chitosan solution (0.5% w/w) to be coated. Morphology, mean size, and encapsulation efficiency of chitosan-coated microspheres were evaluated. To assess the mucoadhesive properties of this drug delivery system, the percent of mucin adsorption to the surface of coated microspheres was determined. Microspheres were spherical in shape. Encapsulation efficiency of different microsphere formulations varied from 78% to 92%. According to the mucin adsorption results, this particulate system showed suitable mucoadhesive properties. It can be concluded that surface modification of microspheres by chitosan coating would increase the prospects of their usefulness as oral drug delivery systems for CyA.     

SiO2空心微球的制备表征及摩擦性能

以分散聚合法制备的聚苯乙烯(PS)微球为有机模板, 以正硅酸四乙酯(C₈H₂₀O₄Si)为无机前躯体物料, 通过静电吸附作用成功地制备了纳米 PS-SiO₂ 复合微球和SiO₂单分散空心结构。通过红外(FTIR)、热重(TG)、透射电镜(TEM)、扫描电镜(SEM) 和热重分析仪(TGA)等手段对纳米复合材料进行了表征, 并对产物的抗磨性能进行了测试。结果表明, 该方法可一次性制备大量的复合微球, 这些微球的直径约为0.7 μm, 分散性能良好。在煅烧去除模板后, 得到了保持完整的空心纳米 SiO₂ 结构, 微球的球壳稳定性较好。摩擦实验表明, 添加了2 wt%空心微球的植物油在较低载荷工况下具有优异的减磨性能, 摩擦系数可低至0.058。      

Preparation and in vitro bioactivity of poly(d,l-lactide) composite containing hydroxyapatite nanocrystals

The nano-sized hydroxyapatite (n-HA) was incorporated into poly(d,l-Lactide) (PDLLA) to form a bioactive and biodegradable composite for application in hard tissue replacement and regeneration. Thin film of PDLLA composite containing 20 mass% of n-HA fillers was successfully developed through integration of solvent co-blending and hot pressing techniques. firstly, n-HA and PDLLA were chemically synthesized, respectively, then mixed together and homogeneously dispersed in N,N-dimethyl formamide(DMF) solvent, finally, the dried blended hybrid containing PDLLA matrix and n-HA fillers was put into the mould and compacted by hot-pressing machine under 8 MPa pressure at 110 °C for 15 min. In vitro studies were conducted using the simulated body fluid(SBF). Composite specimens were soaked in SBF from 1 day to 21 days prior to surface analysis. Results obtained from scanning electron microscopy(SEM) examination, Energy dispersive X-ray detector(EDX) analysis and X-ray diffraction (XRD) analysis showed that a layer of non-stoichiometric apatite formed within 7 days on HA/PDLLA composite surface after its immersion in SBF, demonstrating moderate in vitro bioactivity of n-HA/PDLLA composite, though a moderate rate of apatite formation in SBF was found on initial stage of immersion periods for n-HA/PDLLA composite, compared to the other biomaterial composite. This type of composite film exhibited certain desirable bioactive characteristics, and they are promising bone candidates to develop novel bioactive composites for biomedical application.