阿司匹林-蒙脱土-壳聚糖缓释微球的制备及其体外释放性能

利用溶液法预先制备壳聚糖(Cs)-蒙脱土(MMT)复合材料(Cs-MMT),以Cs-MMT、Cs为原料,采用反相悬浮聚合法制得一种新型药物缓释体系阿司匹林-蒙脱土-壳聚糖载药微球(Asp-MMT-Cs)。采用FT-IR、SEM表征了Cs-MMT和Asp-MMT-Cs载药微球的结构及形态;设计正交实验优化了Asp-MMT-Cs载药微球的制备工艺;通过体外释放实验探讨了载药微球在不同模拟释放液中的释药规律。结果表明:所得微球球形度好,粒径分布较均匀;最优工艺制得的载药微球平均粒径为81.20μm,载药量为9.61%,包封率为76.78%。该缓释体系具有pH敏感性,更倾向于在pH较高的磷酸盐缓冲溶液中释放。     

香草醛交联壳聚糖载药微球的性能及其成球机理分析

以壳聚糖溶液为水相、液体石蜡为油相形成油包水型乳液, 以香草醛为交联剂, 采用乳化交联法制得壳聚糖微球. 结合IR光谱和XRD测试, 分析了壳聚糖交联固化成球的机理: 壳聚糖和香草醛之间所发生的Schiff碱反应和氢键的形成以及缩醛化反应, 以此为基础共同形成交联结构从而使壳聚糖交联固化成球. 探讨了交联后壳聚糖微球结晶度降低的原因: 壳聚糖固化时分子链未充分进行有序的结晶排列, 交联后的壳聚糖结构较复杂, 从而破坏了原壳聚糖分子的规整性. 选用盐酸小檗碱为模型药物, 制备了香草醛交联的壳聚糖载药微球, SEM结果显示, 载药微球表面致密且球形度好, 微球粒径在5-15 μm之间. 此外, 采用分光光度计对载药微球的载药率、药物包封率和药物体外释放性质进行了测试和分析, 结果表明载药微球缓释效果明显.     

5-氟尿嘧啶/壳聚糖载药纳米微球的制备及性能

以三聚磷酸钠为交联剂,采用离子交联法制备了5-氟尿嘧啶/壳聚糖纳米微球,评价其性能、体外释药性能及对人肺癌细胞GLC-82的体外杀伤效应,并通过Zeta电位和红外光谱分析载药纳米微球形成机理.结果表明,所制备的5-Fu/CS纳米微球平均包封率为32.3%,平均载药量为25.6%,平均粒径为253nm,平均zeta电势为+8.38mV,成球性及分散性良好.CS载药纳米微球具有缓释性能,体外释药行为符合双向动力学规律.在体外作用72h,CS载药纳米微球对人肺癌细胞GLC-82的杀伤率达66.6%,杀伤效果明显优于5-Fu对照组.     

双重载药多层海藻酸盐-壳聚糖缓释微球的制备及体外释放

采用滴注法将海藻酸钠与钙离子交联,制成负载血管内皮生长因子(VEGF)的藻酸钙核心球,利用层层自组装技术在核心球的表面依次包覆壳聚糖、海藻酸和壳聚糖,壳聚糖中负载万古霉素(VAN),形成多药载药缓控体系.采用正交实验考察海藻酸钠浓度、钙离子浓度及壳聚糖浓度对VEGF和VAN的药物包封率和载药量的影响,优化了制备工艺.采用扫描电子显微镜观察多层微球的表面、截面形貌及粒径,采用傅里叶变换红外光谱检测海藻酸盐与壳聚糖的自组装情况,分别采用酶联免疫吸附(ELISA)双抗体夹心法和紫外分光光度法检测VEGF和VAN的包封率、载药量及体外释放情况.结果表明,海藻酸钠最优浓度为0.04g/mL,氯化钙最优浓度为0.15g/mL,壳聚糖最优浓度为0.01g/mL.微球光滑圆整,均质实心,直径900~1100μm,VEGF的包封率达61.31%,VAN的包封率为3.48%.体外释放实验结果表明,VEGF缓释时间为15.5d,并出现2个释放高峰;VAN缓释时间为4.5d,释药情况平稳持续,无明显突释.双重载药多层包覆微球兼具控制感染和促进血管生成两种潜能,有望应用于组织工程骨的基础研究和临床实践.     

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.     

壳聚糖接枝β-环糊精聚合物空心微球的制备及其载药性能

以壳聚糖(CS)和β-环糊精(β-CD)为原料,制备了壳聚糖接枝β-环糊精聚合物(CS-g-CD),然后以三聚磷酸钠(TPP)为交联剂,通过静电自组装的方法得到了聚合物空心微球,并以5-氟尿嘧啶(5-FU)为模型药物,研究了聚合物空心微球对药物的负载性能。利用红外光谱(FT-IR)、元素分析、X-射线衍射(XRD)表征了聚合物的结构和组成,激光粒度仪和透射电子显微镜(TEM)表征了聚合物微球的粒径及形貌。通过紫外可见分光光度计研究了微球对药物的载药量和包封率。结果表明,得到的微球呈现较为规则的空心结构,粒径在300~350nm左右,分散性较好,对药物载药量和包封率较高。     

壳交联pH响应型PLGA载药微球的制备与研究

首先采用一次乳化法制备出PLGA[聚(乳酸-羟基乙酸)]纳米微球,并通过静电吸附将阳离子聚合物壳聚糖修饰到PLGA微球表面,然后以香草醛为交联剂对壳聚糖进行化学交联,得到一种壳交联的p H响应型纳米微球(PCV),微球粒径为(277.60±38.01)nm,表面电位为(21.60±4.51)m V.微球稳定性评价结果显示微球在24 h内粒径变化较小;流式细胞仪检测显示细胞对PCV微球的摄取量比未经修饰的PLGA微球的摄取量高;空白微球细胞毒性实验表明在空白微球浓度小于80μg/m L时细胞的存活率达93.24%.以多西他赛(DTX)为模型药物进行包载,该纳米微球DTX的载药率为7.48%,包封率为34.98%;体外药物释放实验显示,该微球在p H=5.0环境下孵育90 h的药物积累释放率达58.66%,而在p H=7.4的环境下的药物积累释放率为50.63%;此外,载DTX微球毒性试验结果表明该载药微球对A549肺癌细胞有较强的杀伤作用,其IC50值可达0.0009μg/m L.     

聚羟基丁酯酯缓释微球的制备及性能

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３０～４０μｍ,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     

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。     

羧甲基壳聚糖/有机累托石纳米复合材料及其药物缓释性能研究

利用简单的溶液插层法制备了羧甲基壳聚糖/有机累托石纳米复合材料,其中累托石(REC)用十六烷基三甲基溴化铵进行改性.用X-射线衍射(XRD)、红外光谱(FTIR)和扫描电镜(SEM)表征了该纳米复合材料的微观结构和形态,实验表明羧甲基壳聚糖插层进入了累托石层间,增大了累托石的层间距,并且累托石均匀地分布在羧甲基壳聚糖基体中.以牛血清蛋白(BSA)为药物模型,研究了纳米复合材料与海藻酸钠形成的微球的药物缓释性能.结果显示,该微球对药物的包封率及缓释性能与纯羧甲基壳聚糖微球相比都有较大改善,包封率从56%提高到86%,药物缓释时间从24 h上升到72 h.并且纳米复合材料/海藻酸钠微球的释药具有pH响应性,在pH为1.2的条件下释药慢,而在pH为7.4时释药快,可用于小肠或结肠定位缓释系统.因此,羧甲基壳聚糖/有机累托石纳米复合材料很有潜力作为药物载体.     

Preparation of thermoresponsive and pH-sensitivity polymer magnetic hydrogel nanospheres as anticancer drug carriers

In this work, a novel thermo and pH responsive magnetic hydrogel nanosphere poly(N-isopropylacrylamide-co-acrylic acid)/Fe(3)O(4) (poly(NIPAAm-co-AA)/Fe(3)O(4)) has been successfully prepared. The magnetic hydrogel nanospheres with thermo and pH-sensitivity were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared-spectrometer (FT-IR), UV-vis absorption spectroscopy, and vibrating sample magnetometer (VSM). The magnetic hydrogel nanospheres exhibited uniform sphere structures and superparamagnetic property. Finally, the drug loading capacities and the releasing behavior of the magnetic hydrogel nanospheres were investigated with doxorubicin hydrochloride (DOX) as an anticancer drug model. The resulting magnetic hydrogel nanospheres exhibited high encapsulation efficiency (95%) to DOX under an appropriate condition. In vitro release experiments revealed that release was faster at pH 5.3 (37°C) than at pH 7.4 (25°C) or pH 7.4 (37°C). The DOX-loaded magnetic hydrogel nanospheres also showed enhanced anticancer effect compared with the free drug in vitro. These presented results suggested that the magnetic hydrogel nanospheres have a potential as tumor targeting drug carrier.     

pH-sensitive polyelectrolyte complex gel microspheres composed of chitosan/sodium tripolyphosphate/dextran sulfate: swelling kinetics and drug delivery properties

Porous chitosan (CS) polyelectrolyte complex (PEC) hydrogel microspheres were prepared via either wet phase-inversion or ionotropic crosslinking with sodium tripolyphosphate (Na+ - TPP) and dextran sulfate (DS). The resulting microspheres were characterized using scanning electron microscopy (SEM) and elemental analysis (EA). The controlled release behavior of ibuprofen (IBU) from these microspheres was investigated. The PEC microspheres were about 700-950 microm in diameter with large pores and open porous structure. The CS/TPP/DS microspheres resisted hydrolysis in strong acid and biodegradation in enzymatic surroundings. The swelling kinetics for CS microspheres was close to Fickian diffusion, whereas those for CS/TPP and CS/TPP/DS were non-Fickian. Furthermore, the equilibrium water content (EWC) and water diffusion coefficient (D) increased with the pH of the media. The release profiles of IBU from CS/TPP/DS microspheres were slow in simulated gastric fluid (SGF, pH 1.4) over 3 h, but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 6 h after changing media. Overall the results demonstrated that CS/TPP/DS microspheres could successfully deliver a hydrophobic drug to the intestine without losing the drug in the stomach, and hence could be potential candidates as an orally administered drug delivery system.     

壳聚糖-g-聚甲基丙烯酸凝胶粒的制备及其药物释放行为

以壳聚糖和甲基丙烯酸为原料,硝酸铈铵为引发剂,合成了不同接枝率的壳聚糖-g-聚甲基丙烯酸(CS-g-PMAA),用FTIR、1H NMR和元素分析表征了产物的结构,以柠檬酸三钠和戊二醛为交联剂制备了具有核壳结构的CS-g-PMAA载药体系。 用UV/Vis检测了CS-g-PMAA粒子对模型药物的释放行为。 结果表明,CS-g-PMAA接枝率为12.21%时药物释放速率最慢,其在pH=1.8介质中药物累积释放量(11 h)为44.18%,而壳聚糖粒子的累积释放量高达65.24%,即接枝改性壳聚糖粒子对药物的缓慢控制释放性能较好; CS-g-PMAA粒子的释药行为还依赖于介质的pH值和盐浓度,在低pH值和低盐浓度下,药物释放速率较快;酶环境下由于载体材料的降解使药物释放速率加快。 分析了不同条件下CS-g-PMAA载药粒子中药物的释放机理。     

Highly Stable Amorphous Calcium Phosphate Porous Nanospheres: Microwave‐Assisted Rapid Synthesis Using ATP as Phosphorus Source and Stabilizer,and Their Application in Anticancer Drug Delivery

Highly stable amorphous calcium phosphate (ACP) porous nanospheres with a relatively uniform size and an average pore diameter of about 10 nm have been synthesized by using a microwave‐assisted hydrothermal method with adenosine 5′‐triphosphate disodium salt (ATP) as the phosphorus source and stabilizer. The as‐prepared ACP porous nanospheres have a high stability in the phosphate buffer saline (PBS) solution for more than 150 h without phase transformation to hydroxyapatite, and the morphology and size were essentially not changed. The important role of ATP and effects of experimental conditions on the formation of ACP porous nanospheres were also investigated. The ACP porous nanospheres were characterized by X‐ray powder diffraction (XRD), Fourier‐transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). This method is facile, rapid, surfactant‐free and environmentally friendly. The as‐prepared ACP porous nanospheres are efficient for anticancer drug (docetaxel) loading and release. The ACP porous nanosphere drug‐delivery system with docetaxel shows a high ability to damage tumor cells, thus, is promising for the application in anticancer treatment.     

Preparation and Drug Release of PVA Composite Nanofibers Loaded Chitosan Microsphere

In this paper, we reported the fabrication of poly(vinyl alcohol)-chitosan (PVA-CS) microspheres composite nanofibers by electrospinning technique. The chitosan microspheres were firstly prepared by electrospray with the solution of chitosan and combretastatin A4. The morphology and size distribution of chitosan microspheres were analyzed by scanning electron microscopy. The influencing factors including the concentrations of both PVA and CS microspheres were studied. The physical properties of the composite nanofibers were characterized by X-ray diffraction (XRD). The drug release rate, MTT toxicity test, and cell culture were also investigated in detail. Results indicate that the chitosan microsphere-loaded composite nanofibers can be prepared when the PVA concentration is 120 mg/mL. The continuity of the nanofibers was influenced by the concentration of CS microspheres. The characteristic peaks of CS or PVA were not observed in the diffractograms after the CS and PVA were processed using the high-voltage electrostatic technique. In addition, the drug release rate showed that nanofibers induce an obvious slow-release effect. Composite nanofibers were non-toxic to fibroblasts cells, and the fibroblasts cells could proliferate on the nanofiber mat.     

Surfactant-assisted fabrication PbS nanorods, nanobelts, nanovelvet-flowers and dendritic nanostructures at lower temperature in aqueous solution

PbS nanostructures with different morphologies, such as rod-like, belt-like, downy-velvet-flower-like and dendrite-like, were fabricated successfully under varied reaction conditions in aqueous solution at lower temperature by the assistance of surfactant CTAB. Especially, among all the synthesis methods for PbS nanocrystals, this is the first report using basic acetate of lead, which was formed at initial reaction stage, as a precursor to control the crystal nucleation rate. This synthesis method is a promising one to metal sulfide for its easy control, low-cost and large-scale production. X-ray powder diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), field-emission scanning electron microscopy (FE-SEM) and UV-visible spectrophotometer (UV-vis) were used to characterize the products. A rational mechanism is proposed and three control factors to the crystal directional growth are also concluded.     

ZnO/C纳米球的亚甲基蓝单吸附特性:平衡、动力学及机理

采用电弧放电法制备了ZnO/C纳米球,利用FESEM、XRD和N₂吸附/脱附测试进行了表征。在避光条件下研究了复合材料对亚甲基蓝的吸附性能。研究结果表明,随着亚甲基蓝的浓度及接触时间的增长吸附量明显上升,在吸附时间为150 min时达到吸附平衡。采用Langmuir、Freundlich及Temkin等温吸附模式对吸附平衡进行了研究。结果表明,吸附等温线符合Langmuir等温吸附模式,单层吸附饱和容量可达188.68 mg·g^-1。利用动力学模型、内扩散模型和外扩散速率控制模型拟合实验数据,拟合数据表明其动力学符合伪二级动力学模型;内扩散机理不是吸附速率的唯一限制机理,亚甲基蓝的总吸附速率受膜扩散控制。     

ZnO/C纳米球的亚甲基蓝单吸附特性:平衡、动力学及机理

采用电弧放电法制备了ZnO/C纳米球,利用FESEM、XRD和N₂吸附/脱附测试进行了表征。在避光条件下研究了复合材料对亚甲基蓝的吸附性能。研究结果表明,随着亚甲基蓝的浓度及接触时间的增长吸附量明显上升,在吸附时间为150 min时达到吸附平衡。采用Langmuir、Freundlich及Temkin等温吸附模式对吸附平衡进行了研究。结果表明,吸附等温线符合Langmuir等温吸附模式,单层吸附饱和容量可达188.68 mg·g^-1。利用动力学模型、内扩散模型和外扩散速率控制模型拟合实验数据,拟合数据表明其动力学符合伪二级动力学模型;内扩散机理不是吸附速率的唯一限制机理,亚甲基蓝的总吸附速率受膜扩散控制。     

羟基磷灰石/聚乙烯醇/壳聚糖水凝胶在模拟体液中的力学性能

从仿生学角度出发,将自制的人工角膜支架材料羟基磷灰石/聚乙烯醇/壳聚糖(n-HA/PVA/CS)浸泡在模拟体液中,对材料的含水率及力学性能进行了测试,并利用扫描电镜、X射线衍射仪、电感耦合等离子体原子发射光谱仪及热重分析仪研究了材料在模拟体液中的形貌、晶体结构、元素组成及热稳定性.结果表明,在模拟体液中,n-HA/PVA/CS复合水凝胶的含水率为80%~86%,具有较高的拉伸强度,能承受正常眼压,且热稳定性较好.在浸泡后期,n-HA/CS/PVA复合材料对Ca2+的吸附和释放达到动态平衡;而其表面含有微量的纳米羟基磷灰石沉积,有利于纤维细胞的长入.     

PLGA/TiO2纳米药物缓释载体的研究

首先利用硅烷偶联剂(KH550)对纳米二氧化钛表面进行预处理,得到氨基改性的二氧化钛,然后与带有高活性端基的丙交酯-乙交酯共聚物(PLGA)反应,制备纳米药物缓释载体PLGA/TiO2有机-无机杂化材料.通过核磁(1H-NMR)、傅里叶变换红外光谱仪(FTIR)、热重分析(TGA)、扫描电子显微镜(SEM)、透射电子显...