医用淀粉微球降解行为研究及应用

介绍了医用淀粉微球的性质,综述了医用淀粉微的球降解行为研究,介绍了医用淀粉微球降解过程研究、相应数学模型的研究及其在医药领域的应用。     

Behaviors of enzyme immobilization onto functional microspheres

Micron-grade monodisperse PMMA microspheres, whose surfaces were modified with functional groups by co-polymerisation using functional monomer, were prepared via dispersion polymerisation. Characterized by their large specific surface area, high adsorption ability, favourable biocompatibility, these monodisperse micron-sized PMMA microspheres were employed as the supporting material in the enzyme immobilization in present work. The influential factors on the activity of immobilized enzyme including pH, temperature, time etc were preliminarily investigated. The results concluded from the experiments indicated that the immobilization procedure could promote the resistance of enzyme against temperature, pH shift and some other tough reaction conditions meanwhile prolong the enzymatic lifetime for storage.     

The in vitro and in vivo anti-tumor effects of MTX-Fe3O4-PLLA-PEG-PLLA microspheres prepared by suspension-enhanced dispersion by supercritical CO2

The in vitro and in vivo anti-tumor efficacy of methotrexate-loaded Fe3O4-poly-L-lactide-poly(ethylene glycol)-poly-L-lactide magnetic composite microspheres(MTX-Fe3O4-PLLA-PEG-PLLA MCMs,MMCMs),which were produced by co-precipitation(C)and microencapsulation(M)in a supercritical process,was evaluated at various levels:cellular,molecular,and integrated.The results at the cellular level indicate that MMCMs(M)show a better anti-proliferation activity than raw MTX and could induce morphological changes of cells undergoing apoptosis.At the molecular level,MMCMs(M)lead to a significantly higher relative mRNA expression of bax/bcl-2 and caspase-3 than MMCMs(C)at 10μg mL-1(P0.01);and the pro-caspase-3protein expression measured by Western blot analysis also demonstrates that MMCMs(M)can effectively activate pro-caspase-3.At the integrated level,mice bearing a sarcoma-180 tumor are used;in vivo anti-tumor activity tests reveal that MMCMs(M)with magnetic induction display a much higher tumor suppression rate and lower toxicity than raw MTX.Pharmacokinetic studies show that MMCMs(M)with magnetic induction significantly increase the accumulation of MTX in the tumor tissue compared with the other treatments.These results suggest that the MMCMs(M)prepared by the SpEDS process have great potential to play a positive role in the magnetic targeted therapy field.     

Nickel oxide hollow microsphere for the chemiluminescence determination of tuberculostatic drug isoniazid

In this article, nickel(II) oxide (NiO) hollow microspheres (HMSs) were fabricated and used to catalyze chemiluminescence (CL) reaction. The studied CL reaction is the luminol-oxygen reaction that was used as a sensitive analytical tool for measuring tuberculostatic drug isoniazid (IND) in pharmaceutical formulations and water samples. The CL method was established based on the suppression impact of IND on the CL reaction. The NiO HMSs were produced by a simple hydrothermal method and characterized by several spectroscopic techniques. The result of essential parameters on the analytical performance of the CL method, including concentrations of sodium hydroxide (NaOH), luminol, and NiO HMSs were investigated. At the optimum conditions, the calibration curve for IND was linear in the range of 8.00 × 10⁻⁷ to 1.00 × 10⁻⁴ mol L⁻¹ (R² = 0.99). A detection limit (3S) of 2.00 × 10⁻⁷ mol L⁻¹ was obtained for this method. The acceptable relative standard deviation (RSD) was obtained for the proposed CL method (2.63%, n = 10) for a 5.00 × 10⁻⁶ mol L⁻¹ IND solution. The mechanism of the CL reaction was also discussed.     

Application and characterization of magnetic chitosan microspheres for enhanced immobilization of cellulase

In this study, a unique carrier magnetic chitosan microspheres (MCTS) was simply synthesized by anchoring Fe₃O₄ onto chitosan for direct immobilization of cellulases cross-linked by gluteraldehye. The structure and morphology were characterized using FT-IR, TGA, VSM and SEM. The optimum immobilization conditions were investigated: immobilized pH 7.0, amount of enzyme 15?mL (0.1?mg/mL), immobilization temperature 30?°C, immobilization time 5?h. At optimum conditions, MCTS achieved maximum enzyme solid loading rate of 73.5?mg/g, while recovery of enzyme activity approached to 71.6%. In the recycle test, immobilized cellulases operated without significant loss in its initial performances after 3 cycles, which indicated that immobilized cellulases can be regenerated and reused. The immobilized enzyme has better values of thermal and storage stability than that of free enzyme. Therefore, MCTS may be considered as a candidate with potential value of application in large-scale operations for cellulases immobilization.     

均匀设计法优化硝酸咪康唑微球的制备工艺

目的：以均匀设计法筛选优化硝酸咪康唑苹果酸化壳聚糖微球的制备工艺,提供可控性及预测性,并对微球稳定性和药物释放规律进行研究。方法：采用乳化交联法制备微球。采用U5（53）试验表进行试验,分别考察各处方的制备的微球的形态和粒径、载药量和包封率。利用SPSS软件进行多元线性回归拟合,得到方程及优化工艺条件。结果：优化方程的预测值与实验值之间有较好的吻合性。制备出的微球可以在室温（25℃）条件下保存;微球的药物释放动力学可用一级动力学方程来描述。结论：本实验通过均匀设计法优化硝酸咪康唑微球的制备工艺预测性好且制备的微球性能良好。     

抗生素缓控释给药系统——载药微球的研究与开发

利用具良好生物相容性和生物可降解性的聚合物制得的微球作为一种新型药物载体, 具有良好的缓控释作用,并具有一定的靶向性,可用于口服和注射,在药学领域和临床上有着广阔的应用前景。综述近年来各种抗生素缓控释微球制剂的研究与开发。     

新城疫壳聚糖微球疫苗免疫效果的研究

鸡新城疫是由新城疫病毒引起的鸡的一种急性、烈性、高度接触性传染病,是危害养禽业的最严重疫病之一。控制新城疫最根本的措施是进行有效的疫苗接种,目前常用的疫苗是弱毒活疫苗和灭活疫苗,但二者在实际应用中均存在一定的局限性。口服微球疫苗可以诱导较强的粘膜免疫;同时还能够诱导产生系统的体液免疫和细胞免疫,已成为ND疫苗研究的热点。以壳聚糖为囊材,新城疫La Sota抗原液为芯材,戊二醛为交联剂,制备出新城疫壳聚糖微球疫苗,通过了实验室安全检验和效力检验。将新城疫壳聚糖微球疫苗与LaSota活疫苗和新城疫油乳剂灭活苗分别免疫SPF鸡,利用MTT、血凝抑制法(HI)和ELISA等分别检测不同疫苗免疫后的细胞免疫、体液免疫和粘膜免疫抗体IgA,并在当免疫鸡HI抗体降到23的情况下进行了攻毒试验。结果表明,新城疫壳聚糖微球疫苗安全性好,免疫后可刺激机体产生较强的细胞免疫、体液免疫和局粘膜免疫,具有较好的保护作用。     

细胞骨架蛋白4荧光免疫层析检测方法的建立

采用基于免疫层析技术与荧光微球标记技术相结合的方式,建立一种快速、简单的定量检测肝癌肿瘤标记物的方法。依据双抗体夹心原理,将细胞骨架蛋白4(CKAP4)配对抗体分别作为标记与包被抗体,羊抗兔多抗作为质控线包被抗体,制备CKAP4荧光免疫层析试纸条,并对试纸条的线性、精密性、稳定性等各项性能指标进行评价。结果表明,采用时间分辨荧光微球所制备的CKAP4免疫层析试纸条灵敏度高,特异性好,精密性在15%以内,回收率在85%–115%之间,线性范围为25–1 000 pg/mL,可在37℃稳定保存20 d,与商业化的ELISA试剂盒的相关性良好。结论:初步建立了CKAP4荧光免疫层析方法,能够定量检测血清中CKAP4的含量,且具有快速、灵敏、简便、经济、可单人份操作等优点,有望成为肝癌辅助诊疗的新方法。     

酮戊二酸改性壳聚糖微球的制备及其对来氟米特的缓释

采用反相悬浮法制备交联壳聚糖微球,再与α-酮戊二酸反应生成Schiff碱,以NaBH_4还原制得改性壳聚糖微球.用FT-IR,SEM和XRD进行表征.并以来氟米特(LEF)为模型药物,考察了其缓释效果.结果显示:微球对药物的最大包封率为94%,载药量为62%,在缓释初期2 h内微球平均释放药量的16%,后期则呈现缓慢释放的趋势.本论文采用的微粒的药物承载量和释放速度既保证了药物的药效又降低了药物释放速率过快引起的对人体的不良反应.     

Combining submerged electrospray and UV photopolymerization for production of synthetic hydrogel microspheres for cell encapsulation

Microencapsulation within hydrogel microspheres holds much promise for drug and cell delivery applications. Synthetic hydrogels have many advantages over more commonly used natural materials such as alginate, however their use has been limited due to a lack of appropriate methods for manufacturing these microspheres under conditions compatible with sensitive proteins or cells. This study investigated the effect of flow rate and voltage on size and uniformity of the hydrogel microspheres produced via submerged electrospray combined with UV photopolymerization. In addition, the mechanical properties and cell survival within microspheres was studied. A poly(vinyl alcohol) (PVA) macromer solution was sprayed in sunflower oil under flow rates between 1-100 μL/min and voltages 0-10 kV. The modes of spraying observed were similar to those previously reported for electrospraying in air. Spheres produced were smaller for lower flow rates and higher voltages and mean size could be tailored from 50 to 1,500 μm. The microspheres exhibited a smooth, spherical morphology, did not aggregate and the compressive modulus of the spheres (350 kPa) was equivalent to bulk PVA (312 kPa). Finally, L929 fibroblasts were encapsulated within PVA microspheres and showed viability >90% after 24 h. This process shows great promise for the production of synthetic hydrogel microspheres, and specifically supports encapsulation of cells.     

Biological testing of chitosan‐collagen‐based porous scaffolds loaded with PLGA/Triamcinolone microspheres for ameliorating endoscopic dissection‐related stenosis in oesophagus

ObjectivesEndoscopic submucosal dissection (ESD), a preferential approach for early oesophageal neoplasms, inevitably results in oesophageal strictures in patients. Clinical use of glucocorticoids through submucosal injection is beneficial for inhibiting oesophageal stricture following injury; however, it also has limitations, such as dose loss and perforation. Hence, alternatives to glucocorticoid therapy should be developed.MethodsA novel porous composite scaffold, ChCo‐TAMS, composed of chitosan, collagen‐I and triamcinolone acetonide (TA) loaded into poly (lactic‐co‐glycolic) acid (PLGA) microspheres (TAMS), was successfully constructed and subjected to biological testing to ameliorate oesophageal ESD‐related stenosis.ResultsThe synthesized biomaterials displayed unique properties in inhibiting the activation of macrophages, chemokine‐mediated cell recruitment and fibrogenesis of fibroblasts. Further application of the scaffolds in the rat dermal defect and porcine oesophageal ESD model showed that these novel scaffolds played a robust role in inhibiting wound contracture and oesophageal ESD strictures.ConclusionsThe developed composite scaffolds provide a promising clinical medical device for the prevention of post‐operative oesophageal stricture.     

Smart latexes for bioseparation

Monodisperse, thermosensitive microspheres with sub-micron diameters are used for separation and collection of proteins and other biomolecules. The thermosensitivity gives the microspheres two valuable features. One is the controllability of affinity between microsphere and protein with temperature. The quality and quantity of proteins to be adsorbed on the microspheres can be controlled with temperature. The other feature is reversible control of dispersion stability. Microspheres which have adsorbed target proteins in the dispersion can be easily recovered by changing temperature. This revised version was published online in July 2006 with corrections to the Cover Date.     

制备复合生长因子的缓释微球并考察其对细胞的影响

目的:制备复合碱性成纤维细胞生长因子的可降解缓释微球,考察其生物活性保存情况,以及其对上皮细胞的作用。方法:采用改良的乳化冷凝法交联制备明胶缓释微球,将其加入上皮细胞的培养液中,用细胞计数法、四甲基偶氮唑盐微量反应比色法(MTT法)测定细胞增殖情况。结果:缓释微球平均粒径12.36±3.56μm;培养1 d后各组细胞计数、吸光度(D)值差异均无显著性意义;5d后,缓释微球组细胞计数、吸光度(D)值明显高于对照组;7 d后,缓释微球组值仍高于其它组,但差异无显著性意义。结论:复合生长因子的缓释微球制备工艺简便,成球性好;能较长时间持续释放活性生长因子,明显促进细胞增殖。     

基于rV270抗原的鼠疫多孔微球疫苗的制备及其免疫保护作用评价

目的：评价生物可降解高分子材料多孔微球作为鼠疫亚单位疫苗佐剂的可行性。方法：制备可生物降解的高分子材料多孔微球,将rV270抗原蛋白吸附到多孔微球中制备微球疫苗,肌肉注射免疫BALB/c小鼠,初次免疫后21d加强免疫1次,于初次免疫后第10周用600LD50鼠疫耶尔森氏菌攻毒,攻毒后观察14d。结果：攻毒后,微球疫苗免疫的小鼠全部存活,且健康状况良好,对照组小鼠几乎全部死亡。结论：生物可降解多孔微球可作为免疫佐剂用于鼠疫亚单位疫苗研制。     

Immobilized β-glucosidase on magnetic chitosan microspheres for hydrolysis of straw cellulose

β-Glucosidase immobilized on magnetic chitosan microspheres for potential recycling usage in hydrolysis of cellulosic biomass was investigated. The immobilized enzyme had an activity of 6.4 U/g support under optimized condition when using cellobiose as substrate. Immobilization resulted in less increase of the apparent K_m, low drift of the optimal pH, as well as improved stability relative to the free enzyme. The immobilized β-glucosidase was applied to enzymatic hydrolysis of corn straw to produce 60.2 g/l reducing sugar with a conversion rate of 78.2% over the course of a 32-h reaction. This conversion rate was maintained above 76.5% after recycling the enzyme for use in eight batches (total 256 h), showing favorable operational stability of the immobilized enzyme.     

自制多孔微球高密度培养Vero细胞的初步研究

多孔微球是动物细胞高密度培养的有效手段,它是1985年由Verax公司开创的,最初用于流化床生物反应器生产单克隆抗体,后来又出现了Percell和Siran系统系列多孔微球,并且使用的反应器种类和生产的产品都在增加,于是便成为一种新型的细胞培养手段而日益受到人们的重视。为此,我们在利用微载体进行Vero细胞高密度培养的同时,又对多孔微球的制备和培养工艺作了初步探索。