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。     

可控尺寸的壳聚糖微球制备

以壳聚糖为单体,戊二醛为交联剂,采用反相悬浮-化学交联法制备了不同条件下的壳聚糖微球。实验结果表明:随着冰乙酸浓度、壳聚糖浓度和乳化剂含量的增大,微球粒径先减小后增大;而随着搅拌速度的增大,微球粒径呈逐渐减小的趋势,控制成球的反应条件可以制备出不同粒径的壳聚糖微球,并在此基础上探讨了微球的生长机理。     

生物相容壳聚糖/蒙脱土复合微球的溶胀与药物缓释性能研究

利用反相乳液聚合法制备出具有良好生物相容性的壳聚糖/蒙脱土复合微球,其中改性蒙脱土作为插层改性剂引入。用X射线衍射和红外光谱分析了改性蒙脱土的结构,以阿司匹林为模型药物,以药物包埋法制备出了壳聚糖/蒙脱土载药微球,并对其缓释性能进行探讨。结果表明,改性蒙脱土的层间距变大,随着蒙脱土含量的增大,复合微球的溶胀率降低,释药率逐渐减小,pH值为1.2下的壳聚糖/蒙脱土载药微球的释药模式为Fickian扩散类型,pH值为7.4下的释药模式为non-Fickian扩散,壳聚糖/蒙脱土复合微球作为药物载体很有潜力。     

不同脱乙酰度壳聚糖的制备及结构性能的研究

壳聚糖目前是天然可降解医用材料的研究热点,但因脱乙酰度(D.D.)为60%～80%的壳聚糖难于制备,国内外对不同脱乙酰度壳聚糖的生物相容性研究少见报导.探索了不同脱乙酰度壳聚糖的制备工艺及D.D.对壳聚糖结构和性能的影响,为进一步研究不同脱乙酰度壳聚糖降解产物对内皮细胞行为的影响做准备.方法:以高脱乙酰度壳聚糖为原料制备中、低脱乙酰度壳聚糖,用酸碱滴定法测定D.D.,粘度法测定分子量,傅利叶红外光谱和X射线衍射法分析晶体结构.结果:制备得到的壳聚糖D.D.分别为54%、61%、63%、70%、80%;D.D.降低使壳聚糖分子量增加,结晶度降低,水溶性和成膜性能改善.表明在乙酰化反应中控制均相条件和乙酸酐用量,能解决D.D.在60%～80%间的壳聚糖难制备的问题.     

NaCl改性SiO_2微球的制备及其自组装光子晶体研究

为提高SiO2微球的表面电荷密度,通过改进Stober法,引入电解质NaCl合成SiO2微球,并采用垂直沉积法制备出光子晶体.通过Zeta电位粒度仪、带EDS能谱仪的场发射扫描电子显微镜(SEM)和紫外-可见-近红外光谱仪对其电学性能、显微形貌和光学性能进行测试分析.Zeta电位测试结果显示改性SiO2:微球的Zeta电位平均提高11.39mV;EDS能谱分析表明微球中含有钠元素;SEM照片表明样品平均粒径为334 nm,平均标准偏差小于5%,所得光子晶体为面心立方密排结构;吸收光谱表明在725nm处具有光子晶体带隙.     

改性纳米SiO2微球的制备及其在果蔬保鲜中的应用

采用溶胶-凝胶法制备纳米SiO_2微球并对其接枝改性,与壳聚糖/淀粉溶液复合后应用于圣女果保鲜包装中。通过扫描电镜、红外光谱、粒径分析等表征,考察纳米SiO_2成球工艺参数和接枝改性效果;并研究了添加不同质量分数的改性纳米SiO_2微球对壳聚糖/淀粉/纳米SiO_2复合膜溶液保鲜效果的影响。结果表明:添加5 m L浓氨水、2.8 m L正硅酸四乙酯、40 m L乙醇并通过缓慢滴加的方式制备得到的微球粒径均一、分散性好;经硅烷偶联剂KH550接枝改性后的纳米SiO_2微球,能够改善复合膜的多项性能;当添加质量分数为3%的改性纳米SiO_2微球时,壳聚糖/淀粉/纳米SiO_2复合膜的保鲜效果较好。     

水溶性壳聚糖的制备及表征

以高脱乙酰化的壳聚糖为主要原料 ,在乙酸水溶液 -乙醇 -吡啶介质中 ,实现了壳聚糖的 N位均相乙酰化反应 ,制备了脱乙酰度为 5 0 %左右 ,在 p H=1～ 14范围内具有良好水溶性的壳聚糖。重点考察了乙酸酐用量对脱乙酰度的影响 ,结果表明 ,当乙酸酐用量与壳聚糖的摩尔比在 2 .0左右时 ,产物的脱乙酰度接近 5 0 % .通过对所用的高脱乙酰度壳聚糖特性粘度 [η]的测定 ,间接得到了产物的分子量为 1.66×10 5左右。对产物进行了 FT- IR及 1H- NMR表征 ,谱图中与乙酰胺基有关的信号均发生了变化 ,表明了乙酰化反应的发生。     

载银壳聚糖微球的制备及其抗菌性研究

采用乳化交联法制备出载银壳聚糖微球,考察了壳聚糖相对分子质量、乳化剂用量、油水比和硝酸银浓度对微球形貌和载银量、包封率的影响,并通过抑菌圈实验对其抗菌性能进行了评价。结果表明:较低相对分子质量的壳聚糖有利于微球制备,而且所得的粒径较小,其粒径介于1～3μm,载银量可高至256 mg/g,银的包封率可达66.8%。抗菌试验结果表明,无银壳聚糖微球对大肠杆菌和金黄色葡萄球菌有一定的抑菌性,加载银后的微球则具有极为显著的抗菌效果。     

双氧水法降解制备低聚壳聚糖工艺探讨

降解程度不同的壳聚糖具有不同的应用性能。从壳聚糖的水解度和脱乙酰度,比较详细地分析双氧水降解高聚壳聚糖时各工艺因素的影响,为制备各种低聚壳聚糖提供参考依据。     

LAS与聚醚复合乳液体系中苯乙烯的聚合

苯乙烯的初始浓度为36.33%时,在十二烷基笨磺酸钠(LAS)/聚醚复合乳液体系中制备了粒径在90.1nm、多分散系数在0.1的聚苯乙烯纳米微球.用红外光谱仪、透射电子显微镜、Zeta电位粒度仪对产物的化学结构,粒径大小、形貌,单分散性进行了表征.研究了体系中各组分质量浓度的改变对产物粒径及单分散性的影响.     

Formulation of chitosan-TPP-pDNA nanocapsules for gene therapy applications

The encapsulation of DNA inside nanoparticles meant for gene delivery applications is a challenging process where several parameters need to be modulated in order to design nanocapsules with specific tailored characteristics. The purpose of this study was to investigate and improve the formulation parameters of plasmid DNA (pDNA) loaded in chitosan nanocapsules using tripolyphosphate (TPP) as polyanionic crosslinker. Nanocapsule morphology and encapsulation efficiency were analyzed as a function of chitosan degree of deacetylation and chitosan-TPP ratio. The manipulation of these parameters influenced not only the particle size but also the encapsulation and release of pDNA. Consequently the transfection efficiency of the nanoparticulated systems was also enhanced with the optimization of the particle characteristics. Overall, the differently formulated nanoparticulated systems possess singular properties that can be employed according to the desired gene delivery application.     

表面活性剂对磁流体稳定性及外层包覆结构的影响

采用化学共沉淀法制备粒径分布均匀的纳米Fe3O4颗粒,用油酸钠和聚乙二醇4000(PEG4000)对纳米Fe3O4颗粒进行表面修饰,制得分散稳定的纳米Fe3O4磁流体,通过电动电位(Zeta电位)、粒径测试、离心沉淀、红外光谱分析(FT-IR)和热分析(TG)对修饰后的纳米Fe3O4颗粒进行了稳定性能评价与结构表征。结果表明,油酸钠与纳米Fe3O4颗粒存在两种不同类型的化学键作用;增大油酸钠加入量不会改变Fe3O4颗粒表面包覆结构,但是,其在纳米Fe3O4颗粒表面的吸附量呈先增加后降低的趋势;PEG4000物理吸附于油酸钠包覆的纳米Fe3O4颗粒表面,PEG4000的加入会进一步提高磁流体的稳定性。     

Factorial design analysis and optimisation of chitosan‐based nanogels as controlled release system for gentamicin

The aim of this study was preparation and optimisation of a controlled‐release delivery system to decrease the dose‐dependent side effects of gentamicin. Hydrogel nanoparticles composed of a polycationic polymer (chitosan) and an inorganic polyanion (sodium tripolyphosphate) were fabricated in the presence of gentamicin. An experimental design was drawn upon to determine the optimum condition of nanoparticle preparation. Various features of the nanoparticles including drug loading parameters, particle size distribution, zeta potential and in vitro drug release profile were evaluated. Ultimately, the antimicrobial activity of the gentamicin‐loaded nanoparticles was analysed by determination of the minimum inhibitory concentration (MIC) and the potency test. As a result, the nanocarriers with an average size of about 250 nm (unloaded) and 493 nm (gentamicin‐loaded) were obtained with unimodal distribution and a notable polydispersity index (≤0.3). The drug loading efficiency was between 28 and 32%. The gradual and sustained releases (∼90%) of gentamicin were achieved in 24 h. The MIC and potency test showed no significant decrease in the antibacterial activity of gentamicin‐loaded nanoparticles. The outcomes demonstrated that the optimised chitosan nanogels prepared in this study can be considered as a suitable carrier for a controlled release system.Inspec keywords: hydrogels, nanoparticles, drug delivery systems, particle size, electrokinetic effects, antibacterial activity, nanomedicineOther keywords: factorial design analysis, chitosan‐based nanogels, gentamicin, controlled‐release delivery system, hydrogel nanoparticles, polycationic polymer, inorganic polyanion, sodium tripolyphosphate, particle size distribution, drug loading parameters, zeta potential, in vitro drug release profile, antimicrobial activity, minimum inhibitory concentration, polydispersity index, drug loading efficiency, antibacterial activity     

羟丙基壳聚糖纳米微粒的制备

将壳聚糖与环氧丙烷反应，通过控制反应条件制备出取代度为0．56的羟丙基壳聚糖。改性后的羟丙基壳聚糖水溶性增强，将其配制成适当浓度的水溶液，利用离子凝胶法，与一定浓度的多聚磷酸钠反应，形成了粒径在500～700nm的羟丙基壳聚糖纳米微粒，TEM图像显示制备出的纳米微粒形状规整。     

室温条件下纳米银的温和制备和形貌调控

目的 探究室温条件下不同还原剂以及其他实验助剂在化学还原纳米银过程中对其颗粒粒径、尺寸分布和形貌的影响。方法 以抗坏血酸为还原剂,聚乙烯吡咯烷酮（PVP）为分散剂,柠檬酸钠为保护剂和第2还原剂,选择葡萄糖和硼氢化钠作对照,在室温下通过化学还原的方法来制备纳米银颗粒。通过马尔文激光粒度仪、紫外–可见光谱（UV–vis）、透射电镜（TEM）等对所制备纳米银进行表征。结果 采用抗坏血酸作为还原剂时,通过调控抗坏血酸体积（0.2 mL）,固定柠檬酸钠和PVP体积分别为0.5、0.6 mL,制备出粒径较小（平均粒径为56 nm）且尺寸分布较均一的球形纳米银;采用葡萄糖和硼氢化钠作还原剂时纳米银颗粒尺寸过大（平均粒径分别为216nm和189nm）。结论 采用抗坏血酸作为还原剂,调控柠檬酸钠、PVP等实验参数在最佳范围,更容易制备出球形度好、粒径小的均匀纳米银溶液。     

Preparation, characterization and adsorption properties of chitosan nanoparticles for eosin Y as a model anionic dye

The present study dealt with the adsorption of eosin Y, as a model anionic dye, from aqueous solution using chitosan nanoparticles prepared by the ionic gelation between chitosan and tripolyphosphate. The nanoparticles were characterized by atomic force microscopy (AFM), size and zeta potential analysis. A batch system was applied to study the adsorption of eosin Y from aqueous solution by chitosan nanoparticles. The results showed that the adsorption of eosin Y on chitosan nanoparticles was affected by contact time, eosin Y concentration, pH and temperature. Experimental data followed Langmuir isotherm model and the adsorption capacity was found to be 3.333 g/g. The adsorption process was endothermic in nature with an enthalpy change (DeltaH) of 16.7 kJ/mol at 20-50 degrees C. The optimum pH value for eosin Y removal was found to be 2-6. The dye was desorbed from the chitosan nanoparticles by increasing the pH of the solution.     

Thymopentin-loaded pH-sensitive chitosan nanoparticles for oral administration: preparation, characterization, and pharmacodynamics

Thymopentin, a potent immunomodulating drug, was incorporated into pH-sensitive chitosan nanoparticles prepared by ionic gelation of chitosan with tripolyphosphate anions and then coated with Eudragit S100 to improve the stability and the oral bioavailability. Nanoparticles particle size and zeta potential were measured by photo correction spectroscopy and laser Dopper anemometry. Its morphology was examined by environment scan electron microscope. The encapsulation efficiency and the release in vitro were determined by HPLC. Enzymatic stabilization was expressed by the enzymatic degradation of aminopeptidase. Biological activity of TP5 loaded in nanoparticles was assayed by lymphocyte proliferation test in vitro and the immune function (CD4+/CD8+) of irradiated rat in vivo. The results obtained demonstrated that the average sizes of pH-sensitive chitosan nanoparticles were 175.6 +/- 17 nm, the zeta potential was 28.44 +/- 0.5 mV and the encapsulation efficiency was 76.70 +/- 2.6%. The cumulative release percentages of thymopentin from the pH-sensitive nanoparticles were 24.65%, 41.01%, and 81.44% incubated in different medium, 0.1 N HCl, pH 5.0 PBS, and pH 7.4 PBS, respectively. The pH-sensitive chitosan nanoparticles could efficiently protect TP5 from enzymatic degradation and prolong the degradation half-time of TP5 from 1.5 min to 15 min. It was demonstrated from the lymphocyte proliferation test that the nanoparticle-encapsulated TP5 still kept its biological activity. In immunosuppression rats, the lowered T-lymphocyte subsets values were significantly increased and the raised CD4+/CD8+ ratio was evidently reduced. These results indicated that pH-sensitive chitosan nanoparticles may be used as the vector in oral drug delivery system for TP5.     

Two modelling data analytical methods applied to optimise the preparation of norcantharidin chitosan nanoparticles

In our study, the non-linear regression model and artificial neural networks (ANNs) were used to optimise the preparation of the loading norcantharidin chitosan nanoparticles (NPs) by ionic cross-linkage. Two major indexes, the particle size and the entrapment efficiency of the drug vehicles were synchronously optimised according to the normalised value calculated referring to the weights of the indexes and factors. For the purpose, a multiple regression model was constructed for fitting several preparation factors, including the low molecular weight of chitosan (LCS), sodium tripolyphosphate (TPP) concentrations and the temperature of the ionic cross-linkage reaction. Each of the level values in the factors was arranged using the L₉(3⁴) table and their linear weighted sum of the normalised value was taken as optimised object. A back-propagation (BP) network (3 × 7 × 2) in ANNs was created and trained for further checking the optimal results and the trained network was applied to simulate the experiment system and screen the optimal conditions. Finally, when the weights of temperature, particle size and entrapment efficiency were 0.1, 0.4 and 0.5, respectively, the best preparation condition of NPs was obtained as 131 ± 7 nm of particle size and 45.12% of entrapment efficiency at 40°C.     

壳聚糖/PHB复合缓释微包囊的制备与体外释药评价

用疏水性聚酯PHB外包覆壳聚糖-三聚磷酸钠-阿斯匹林药物缓释体(CPA)制备了壳聚糖/PHB复合缓释微包囊(CPAB),以克服CPA遇酸不稳定的释药特点.用傅立叶红外分光光度计、激光粒度仪、扫描电镜表征了CPAB的组成、粒径及表面形貌.结果显示,CPAB粒径在50～100nm和载药率18.5%时,表面有不均匀的空隙.体外释药评价证实CPAB能有效解决CPA在酸性下的不稳定性,具有长效缓释作用.     

Preparation of N-trimethyl chitosan-protein nanoparticles intended for vaccine delivery

In this paper, various N-trimethyl chitosan (TMC) of different molecular-weights (approximately 100 KD, approximately 200 KD, and approximately 400 KD, respectively) with the approximately degree of quartenization (DQ) of 40% were successfully synthesized. In vitro cytotoxicity of TMC solution showed the dependence of TMC concentration from 20 microg/ml to 500 microg/ml on the relative cell activity. Molecular weight of TMC did not greatly affect the cytotoxicity of TMC against HEK293 and L929 cells. TMC nanoparticles and alginate modified TMC nanoparticles were prepared by the ionic gelation method. Subsequently, we investigated the properties of TMC nanoparticles and alginate modified TMC nanoparticles intending for oral delivery of antigens. Molecular weight of TMC did not affect the loading capacity (LC) and in vitro release behavior of TMC nanoparticles. However, BSA concentration and alginate modification have strongly effect on properties of TMC nanoparticles (particle size; surface charge; loading efficiency and loading capacity). In vitro release behavior indicated that alginate modification could efficiently decrease initial burst release and extend release time in phosphate buffer (PBS, pH 7.4) and acidic solution (0.1 M HCl, pH = 1) at 37 degrees C. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) assay showed that alginate modification could effectively improve the stability of TMC nanoparticles and protect BSA from degradation or hydrolysis in acidic condition for at least 2 h.