壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原的制备及体外释放性能

背景：包裹幽门螺杆菌全菌蛋白抗原的研究仍处于探索阶段,有关壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原的制备工艺及体外释放性能的文献甚少。 目的：探讨幽门螺杆菌全菌蛋白抗原壳聚糖微球的制备工艺及体外释放特性。 方法：采用沉淀法制备壳聚糖微球,筛选最佳制备工艺及配比、包裹时间,并在电镜下观察微球的形态和粒径。采用壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原,BCA法测定幽门螺杆菌全菌蛋白抗原微球的包裹率、包裹量及体外释放率。 结果与结论：终体积分数为1%的冰醋酸、硫酸钠为交联剂、pH 5.0、滴加交联剂时不粉碎处理为壳聚糖微球最佳制备工艺,电镜观察显示微球表面光滑、形态圆整,具有良好的分散性,多数微球粒径为1.0-5.0 μm。幽门螺杆菌全菌蛋白抗原微球的包裹率为80.4%,包裹量为16.4%,48 h总释放率为19.4%,幽门螺杆菌全菌蛋白抗原微球整体呈缓慢释放状态。结果证实,实验制备的壳聚糖微球对幽门螺样菌全菌蛋白抗原具有良好的包裹率和包裹量,幽门螺杆菌全菌蛋白抗原微球整体呈缓慢释放状态。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程      

壳聚糖载氟喹诺酮类药物缓释微球的研究进展

壳聚糖载氟喹诺酮类药物微球是一类新型的抗菌缓释剂,它既具有壳聚糖的抗菌、抑菌性能,又能发挥氟喹诺酮类药物良好的杀菌作用.将氟喹诺酮类药物负载于壳聚糖微球,可大幅提升其抗菌、杀菌及消炎抗感染性能.综述了近几年壳聚糖载氟喹诺酮类药物缓释微球的制备方法及其应用研究进展.     

影响微球药物释放因素的研究

目的 观察影响微球药物释放的因素，为其应用提供理论基础。方法 以可生物降解的聚乳酸—聚乙醇酸共聚物(PLGA)和聚L—乳酸(PLIA)为载体，采用乳化—溶剂挥发法制备含细胞松弛素B(cytoB)微球，以HPLC测定cy-toB含量。结果 制备了不同球径的微球，其球径分别为150nm、500nm、1μm、5μm、10μm和20μm。体外释放实验证明，球径越小，药物释放速度越快；球径相同时，以PLIA为基材的微球比PLGA的释放慢。结论 可通过选择适当的微球大小和基质材料达到所期望的药物释放过程。     

羧甲基壳聚糖作为植入可降解缓释微球辅料的实验研究

羧甲基壳聚糖作为一种高分子材料 ,具有良好的组织相容性和生物可降解性。本实验试图利用羧甲基壳聚糖作为植入环丙沙星微球的缓释辅料 ,并探索这一剂型的制备工艺、结构形态和体外释药特性。首先我们采用乳化交联技术制备微球 ;然后用扫描电子显微镜、红外光谱、及示差热分析等方法研究微球的结构和形态 ;建立体外持续流动释放系统初步检测微球的体外释放特性。实验结果发现 :微球的结构和形态受制备工艺条件如温度、离子强度、搅拌速度等因素的影响 ;一定工艺条件下制备的环丙沙星微球的体外释放时间可达 7d以上 ,释放行为符合 Higuchi方程。因此 ,我们认为 :羧甲基壳聚糖可作为环丙沙星可降解植入微球的缓释辅料 ;乳化交联技术是制备这一微球的有效方法 ,工艺简单、稳定     

幽门螺杆菌全菌蛋白抗原壳聚糖微球体外释放特性

背景：不同方法制备出的幽门螺杆菌全菌蛋白抗原壳聚糖微球,其包裹率和控释效果也不同。 目的：探讨幽门螺杆菌全菌蛋白抗原壳聚糖微球的最佳制备方案,观察其体外释放特性。 方法：使用Berthold沉淀法制备壳聚糖微球,筛选最佳制备方案;使用扫描电镜及粒径分析仪观察壳聚糖微球的形态及粒径分布;冻干后的壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原,使用BCA蛋白定量试剂盒测量分析微球的抗原包裹率、包裹量及释放率。 结果与结论：从32种壳聚糖微球制备方案中筛选出了以海得贝壳聚糖为原料、冰乙酸的浓度为1%、硫酸钠为沉淀剂、pH值为5.0、不进行超声处理方案为最佳制备方案,扫描电镜示微球光滑圆整、致密,粒径分布在1.0~5.0 μm;抗原包裹率为79.92%,包裹量为16.47%;体外释放实验表明,总抗原释放率为20.39%,呈缓慢释放状态。     

聚乳酸载阿奇霉素微球包裹和体外释放行为

以溶剂-挥发法制备的聚乳酸微球为载体材料,阿奇霉素为被包裹药物.通过紫外光谱(UV)和扫描电镜(SEM)研究微球的包裹行为;建立药物的UV回归方程,以高效液相色谱(HPLC)研究载药微球的体外释放行为,并建立药物的HPLC回归方程.结果显示,在阿奇霉素投入量为10%时微球具有较好的形态,而且包封率达到90%;药物的释放为两相释放,第一阶段为暴释,第二阶段为溶蚀释放.研究结果为聚乳酸药物缓释微球进一步应用提供技术和参数支持.     

壳聚糖膜及其改性膜的药物释放动力学研究

利用时间滞后（Lag-time）法,研究药物起始浓度（C0)、膜厚（h)和体系流动速度（v）对壳聚糖膜药物释放动力学参数的影响。结果表明：C0对滞后时间（T0)或扩散系数（D）没有影响;随h增大,T0增大,D值增大;随v增大,T0缩短,D值增大。还制备了N-烷基化壳聚糖膜。实验结果表明,在相同条件下,N-烷基化壳聚糖的T0值比纯壳聚糖膜的T0值小。     

用作药物载体的聚合物微球

聚合物载体 近年来,人们用聚合体系作为药物载体的兴趣日益浓厚。这些体系既可采用可溶性聚合物(与药物形成可生物降解的键),也可采用可生物降解的微球(药物结合于微球中)。概括说来,通常把用于药物输送的聚合物微球归类为胶体载体。胶体载体不仅包括微球和超细     

成骨生长肽壳聚糖-海藻酸钠微球的制备及体外检测

背景：成骨生长肽体外注射可以刺激外周血和骨髓细胞数增加,增加动物的骨量,加速骨折愈合,但因多肽不稳定性及注射应用不方便,限制了其临床应用。 目的：应用乳化交联法制备成骨生长肽壳聚糖-海藻酸钠缓释微球,并对其粒径、载药、体外释药、理化特性进行检测。 方法：以戊二醛作为交联剂,应用乳化交联法制备具有控制释放功能的负载成骨生长肽壳聚糖-海藻酸钠微球,显微镜及扫描电镜观察微球的形态和粒径;利用酶联免疫吸附实验动态检测成骨生长肽壳聚糖-海藻酸钠微球的载药率、包封率和缓释规律。 结果与结论：乳化交联法制备的壳聚糖-海藻酸钠微球,球形良好,球体表面有较多微孔,具有较高的包封率(>72%)。体外药物释放实验表明,成骨生长肽可以从壳聚糖-海藻酸钠微球中缓慢释放,整个释放过程可达49 d,累积释放率>85%。提示应用乳化交联法制备的负载成骨生长肽壳聚糖-海藻酸钠缓释微球,具有很好的控制释放成骨生长肽的能力。     

壳聚糖胰岛素微球在糖尿病大鼠中的降糖作用研究

我们观察了壳聚糖为载体的胰岛素微球的口服制剂对链脲菌素致糖尿病大鼠的降血糖作用.用扫描电镜观察正常大鼠管饲壳聚糖胰岛素微球后1、2、3、7d微球在大鼠体内的分布.18只链脲佐菌素致糖尿病大鼠被随机分成3组壳聚糖胰岛素微球管饲组(120U/kg,n=6);诺和灵中效胰岛素皮下注射组(24U/kg,n=6),空白对照组(管饲等容积的蒸馏水,n=6).另有5只正常大鼠作为正常对照组(管饲等容积的蒸馏水,n=5).分别测定4组大鼠用药前后的血糖值,并做组间分析比较.结果表明(1)壳聚糖胰岛素微球能通过大鼠的小肠吸收,并靶向分布于小肠、肝、脾等器官.(2)壳聚糖胰岛素微球管饲组在管饲微球后第1天,糖尿病大鼠的血糖从24.7±3.2mmol/L下降至16.9±5.5mmol/L,第2天降至最低12.1±5.7mmol/L,第3天开始逐渐回升至用药前水平,血糖最大下降幅度为50.2%.诺和灵中效胰岛素皮下注射组注射胰岛素后,糖尿病大鼠的血糖从25.2±3.8mmol/L下降至10.4±5.2mmol/L,第2天开始逐渐回升至用药前水平,血糖最大下降幅度为58.7%.两组下降幅度比较无统计学差异(P＞0.05).而空白对照组和正常对照组大鼠的血糖无明显变化,但它们分别和前两组比较,具有统计学差异(P＜0.001).因此,我们认为对链脲菌素致糖尿病大鼠,管饲壳聚糖胰岛素微球具有一定程度的降糖效果.     

药物控释用海藻酸钠、壳聚糖、明胶的研究进展

由于许多药物如肽或蛋白质药物,物理化学性质不稳定,在胃肠道中极易降解.因此,在口服释药设计中,pH敏感水凝胶如海藻酸钠、壳聚糖和明胶作为药物控制释放载体日益引起人们的关注.将针对三种天然高分子材料的来源、结构、性能及共混改性展开讨论.     

Poly(l-glutamic acid)/chitosan polyelectrolyte complex porous microspheres as cell microcarriers for cartilage regeneration

In this study a novel kind of porous poly(l-glutamic acid) (PLGA)/chitosan polyelectrolyte complex (PEC) microsphere was developed through electrostatic interaction between PLGA and chitosan. By adjusting the formula parameters chitosan microspheres with an average pore size of 47.5 ± 5.4 μm were first developed at a concentration of 2 wt.% and freeze temperature of −20 °C. For self-assembly of the PEC microspheres porous chitosan microspheres were then incubated in PLGA solution at 37 °C. Due to electrostatic interaction a large amount of PLGA (110.3 μg mg⁻¹) was homogeneously absorbed within the chitosan microspheres. The developed PEC microspheres retained their original size, pore diameters and interconnected porous structure. Fourier transform infrared spectroscopy, thermal gravimetric analysis and zeta potential analysis revealed that the PEC microspheres were successfully prepared through electrostatic interaction. Compared with microspheres fabricated from chitosan, the porous PEC microspheres were shown to efficiently promote chondrocyte attachment and proliferation. After injection subcutaneously for 8 weeks PEC microspheres loaded with chondrocytes were found to produce significant more cartilaginous matrix than chitosan microspheres. These results indicate that these novel fabricated porous PLGA/chitosan PEC microspheres could be used as injectable cell carriers for cartilage tissue engineering.     

A novel study on the mechanisms of drug release in PLGA-mPEG microspheres with fluorescent drug

The purpose of this research was to proof the microspheres release mechanism by a novel method-detecting and comparing the drugs fluorescent changes on the microspheres surface. Fluorescein sodium (FS, 0.4 kDa) and fluorescein isothiocyanate-bovine serum albumin (FITC-BSA, 66.8 kDa) were employed as model drugs. FS and FITC-BSA were encapsulated into PLGA-mPEG microspheres through double emulsion evaporation method, and the drug-loaded microspheres in vitro degradation and release behaviors were evaluated by scanning electron microscope, gel permeation chromatography, confocal laser scanning microscopy (CLSM), BCA assay kit, and UV–vis spectrophotometry. FS-loaded microspheres revealed a severe initial burst release, followed by a sustained release, and we could observe a bright fluorescent on the microspheres surface during the early release period under the CLSM. The bright fluorescent gradually faded out in the later period as only 1~2% FS was remained after 14 days release. FITC-BSA-loaded microspheres revealed a typical tri-phase release profile, and we observed a weak fluorescent on the microspheres surface after the initial burst release, and the fluorescent came bright again after an obvious erosion appeared on the microspheres surface. In the later release stage, the fluorescent gradually faded out as the fast release of FITC-BSA.     

载表柔比星的壳聚糖纳米粒的制备及其特性研究

目的 制备经聚乙二醇修饰的壳聚糖纳米粒(PEG/CS NP),并负载表柔比星(EPI),研究载表柔比星的壳聚糖纳米粒(PEG/CS-EPI NP)体外释药性能.方法 应用阴离子凝聚法制备PEG/CS-EPI NP,透射电镜观察纳米粒的形态特征,激光粒度分析仪测定粒径大小,紫外分光光度法测定纳米粒的载EPI量,动态透析法考察载EPI纳米粒的体外释放特性.结果 当壳聚糖与三聚磷酸钠质量比为6∶1,壳聚糖与EPI质量比为8∶1时,制备的PEG/CS-EPI NP呈圆形或椭圆形,分散性良好,平均粒径(322.1±14.4)nm,载EPI量为(13.9±1.1)%,包封率(74.2±1.8)%,72 h累积释药率达(82.0±2.1)%.结论 采用阴离子凝聚法制备的PEG/CS-EPI NP形状规则、粒度分布均匀,具有较高包封率和较好缓释性能.     

Nitric oxide-releasing chitosan oligosaccharides as antibacterial agents

Secondary amine-functionalized chitosan oligosaccharides of different molecular weights (i.e., ∼2500, 5000, 10,000) were synthesized by grafting 2-methyl aziridine from the primary amines on chitosan oligosaccharides, followed by reaction with nitric oxide (NO) gas under basic conditions to yield N-diazeniumdiolate NO donors. The total NO storage, maximum NO flux, and half-life of the resulting NO-releasing chitosan oligosaccharides were controlled by the molar ratio of 2-methyl aziridine to primary amines (e.g., 1:1, 2:1) and the functional group surrounding the N-diazeniumdiolates (e.g., polyethylene glycol (PEG) chains), respectively. The secondary amine-modified chitosan oligosaccharides greatly increased the NO payload over existing biodegradable macromolecular NO donors. In addition, the water-solubility of the chitosan oligosaccharides enabled their penetration across the extracellular polysaccharides matrix of Pseudomonas aeruginosa biofilms and association with embedded bacteria. The effectiveness of these chitosan oligosaccharides at biofilm eradication was shown to depend on both the molecular weight and ionic characteristics. Low molecular weight and cationic chitosan oligosaccharides exhibited rapid association with bacteria throughout the entire biofilm, leading to enhanced biofilm killing. At concentrations resulting in 5-log killing of bacteria in Pseudomonas aeruginosa (P. aeruginosa) biofilms, the NO-releasing and control chitosan oligosaccharides elicited no significant cytotoxicity to mouse fibroblast L929 cells in vitro.     

Cross-linked chitosan microspheres as carriers for prolonged delivery of macromolecular drugs

Bovine serum albumin (BSA) and diphtheria toxoid (DT) were loaded by passive absorption from aqueous solutions into preformed glutaraldehyde cross-linked chitosan microspheres. In vitro release of BSA under sink conditions at 37°C showed that even though there was a large burst effect, there was a more or less steady increase with time thereafter for several days. Coating the BSA-loaded particles with paraffin oil or with a polymer, such as polylactic acid, modulated drug release. After the initial burst from PLA coated particles, the release rate increased with time for nearly 2 months. Preliminary immunogenicity studies on Wistar rats using DT loaded chitosan spheres showed that the antibody titres were fairly constant over a 5-month period, although very low compared to DT given on alum as control. Histological studies of placebo microspheres intramuscularly injected into rats demonstrated their tissue compatibility. Biodegradation was not complete in 6 months demonstrating the potential of cross-linked chitosan spheres as a long-acting drug delivery vehicle. The study demonstrated the possibility of incorporating biological macromolecules which are very sensitive to organic solvents, pH, temperature, ultrasound, etc. by a passive absorption technique to degradable biopolymer matrices thereby preserving their biological integrity. It is also shown that drugs passively absorbed into such matrices by taking advantage of their swelling behaviour need not necessarily be released completely in the initial 'burst' and a sustained release may be possible for macromolecules thus incorporated.     

Alginate and chitosan particles as drug delivery system for cell therapy

Drug-carrying microstructures which have a size similar to biological structures are very attractive to encapsulate drugs and protect them during the transit in the human body. This paper describes polymeric (alginate and chitosan) particles (average radius 500 nm) produced by homogenization techniques. In vitro studies performed on cell lines demonstrate the effectiveness of such particles for intracellular drug delivery. Our experiments suggest that cellular up - take increases linearly with particle concentration in the growth medium, and the internalization process has a first order kinetics (characteristic time around 0.5 h⁻¹). In addition, the particles degrade within 24 h from the up-take without side effects for cell viability.     

药物信息学在新药发现中的应用和研究进展

<正>药物信息学是应用人类基因组计划产生的大量数据和全球分子生物学研究的结果,探讨发现药物的新靶点、新方法,促进药物研究进程的一门新的交叉学科,涉及生物信息学、化学信息学、计算化学、组合化学等多领域学科,并包括药物代谢动     

1994 whitaker lecture: Polymers for drug delivery and tissue engineering

This paper reviews three areas of the author's research. The first area concerns the development of technologies to release macromolecules continuously from solid polymers. By embedding solid protein (or other macromolecule) powders at the correct concentration in hydrophobic polymers, prolonged release for over 100 days can be achieved. The second area involves the synthesis of new biodegradable polymers specifically designed for drug delivery. A novel family of polymers, polyanhydrides, now being explored in a number of medical applications is examined. The use of these polymers to deliver chemotherapeutic agents locally may provide a new approach to treat brain cancer. The final research topic is in the area of tissue engineering. By placing mammalian cells on biodegradable polymer scaffolds, a variety of tissues have been created in animal models. Cartilage is discussed as a model tissue.     

Facile synthesis of magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan hydrogel as MTX carriers for controlled drug release

In the present study, methotrexate (MTX)-encapsulated magnetic-/pH-responsive hydrogel beads based on Fe₃O₄ nanoparticles and chitosan were successfully prepared through a one-step gelation process, which is a very facile, economic and environmentally friendly route. The developed hydrogel beads exhibited homogeneous porous structure and super-paramagnetic responsibility. MTX can be successfully encapsulated into magnetic chitosan hydrogel beads, and the drug encapsulation efficiency (%) and encapsulation content (%) were 93.8 and 6.28%, respectively. In addition, the drug release studies in vitro indicated that the MTX-encapsulated magnetic chitosan hydrogel beads had excellent pH-sensitivity, 90.6% MTX was released from the magnetic chitosan hydrogel beads within 48 h at pH 4.0. WST-1 assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the MTX-encapsulated magnetic chitosan hydrogel beads had good cytocompatibility and high anti-tumor activity. Therefore, our results revealed that the MTX-encapsulated magnetic chitosan hydrogel beads would be a competitive candidate for controlled drug release in the area of targeted cancer therapy in the near future.