胆固醇对卵磷脂囊泡稳定性的影响

采用透射电子显微镜研究了Gemini表面活性剂诱导卵磷脂囊泡结构改变的机理, 用Langmuir膜天平研究卵磷脂和胆固醇的不溶单分子混合膜在气-液界面的行为和混合膜分子间的相互作用, 并结合动态光散射技术和停留法探讨胆固醇对Gemini表面活性剂诱导卵磷脂囊泡结构改变的影响. 从电镜结果可以推测带正电荷的Gemini表面活性剂分子会嵌入到带负电荷的卵磷脂囊泡双分子层的外层, 囊泡的双分子层之间的相互吸引力使双分子层的厚度减少, 由于嵌入的表面活性剂分子在囊泡的双分子层中分布是不均匀的, 这种分布的不均匀性必然会导致双分子层厚度的不均匀, 从而使囊泡破裂. 混合膜的过剩面积和动力学结果表明, 胆固醇和卵磷脂是相互吸引的, 即胆固醇的加入使卵磷脂囊泡更不容易被表面活性剂破坏.     

主客体超分子囊泡及其药物载运性能研究

伴随着新型主体分子的不断出现,主客体超分子囊泡的研究受到越来越多的关注。环糊精、杯芳烃、葫芦脲和柱芳烃等主体分子均可以和特定结构的客体分子通过主客体识别作用构筑超分子双亲分子,得到的超分子双亲分子可以进一步自组装为主客体超分子囊泡。主客体超分子囊泡是一类具有敏感响应性的囊泡体系,具有制备简单、生物相容性好和易于控制组装等优点。该囊泡体系对外界刺激具有良好的响应性,从而可以实现药物分子的可控运输和释放,使其成为一种性能独特的药物载运系统。本文结合近年来主体分子的发展,首先介绍了环糊精、杯芳烃、葫芦脲和柱芳烃等主客体超分子囊泡的研究进展,然后对该类超分子囊泡的载药途径进行了总结。该囊泡体系不仅可以在囊泡膜层和空腔中载药,还可以在主体分子的空腔中载药。同时,对载药主客体超分子囊泡的不同刺激响应性进行了归纳概括。最后结合该体系现阶段的研究状况,对该类超分子囊泡的发展前景进行了展望。     

脂质体的特异性识别与单颗粒电化学检测

脂质体载药系统已在许多疾病的治疗中发挥重要作用.体外构建并模拟脂质体与生物膜特异性识别相互作用,对于探索脂质体在生物体内的稳定性,开发新型高效和智能化药物递送系统具有重要的现实意义.本文通过分子组装技术构筑了稳定的磷脂囊泡-脂质体,利用微加工技术制备金微电极,然后在其表面进行亲合素修饰,借助电化学工作站检测脂质体单颗粒的碰撞行为,以此建立一种检测脂质体在体外和生物体内存在的技术平台.实验证明,在脂质体中引入生物素分子,通过与微电极表面的亲合素分子产生特异性识别,能显著增加单颗粒碰撞的频率和强度.这些定量的数据为研究脂质体与生物膜动态互作提供了十分有效和准确的检测手段,为验证脂质体载药体系在生物内的稳定性和释放速率建立了新方法.     

离子键交联聚合物囊泡的制备及对药物的负载与释放

通过双亲性接枝共聚物海藻酸钠接枝聚N-异丙基丙烯酰胺(SA-g-PNIPAM)与Ca2+之间的静电作用,在水溶液中制备了温度敏感性离子键交联聚合物囊泡,并以5-氟尿嘧啶(5-FU)为模型药物,研究了聚合物囊泡对5-FU的负载与释放性能。该囊泡疏水性的膜由海藻酸钠与Ca2+之间的静电作用复合形成。透射电镜研究表明,囊泡具有空心结构,直径在100~150nm左右。聚合物囊泡的最低临界溶解温度(LCST)为34.5℃左右。聚合物囊泡对5-FU具有较高的载药量和包封率,其药物释放速率随溶液p H值的增加而降低,随离子强度的增大而增大,表现出良好的环境响应性。     

席夫碱自组装单分子膜的电化学行为

利用自组装技术将席夫碱硫醇衍生物在金表面形成自组装单分子膜,并初步研究了此自组装单分子膜的电化学行为,发现该席夫碱分子在0.1 mol•L－1的KCl溶液中具有电化学不可逆氧化还原行为，且随着自组装时间的增加表观电极反应速率常数值显著减小,最后减小为0,并对此进行了解释.     

杂臂星型嵌段共聚物在溶液中自组装形成囊泡结构的计算机模拟

利用耗散粒子动力学模拟方法, 研究了杂臂星型嵌段共聚物A_m(B_n)₂在溶液中自组装形成囊泡的行为. 主要分析了自组装过程、亲水分枝和疏水分枝的长度及分子构型对组装结构的影响. 结果表明, 杂臂星型聚合物在溶液中会自组装形成碟状胶束, 之后弯曲闭合形成囊泡. 当亲水部分的分枝较短时, 易于形成囊泡结构; 在可形成囊泡结构的条件下, 双分子层囊泡膜的厚度随分枝长度的增加而增加. 与构成相近的线型嵌段共聚物相比, 杂臂星型嵌段共聚物更易形成囊泡结构, 且形成的囊泡结构较薄.     

生物医用高分子囊泡

高分子囊泡由于其独特的腔-膜-冠结构,在生物医用等领域具有重要应用前景.本专论从自组装新机理/新方法和新的生物医学应用两方面总结和评述了近期生物医用高分子囊泡领域的研究进展.前者包括构建高效包载生物大分子的囊泡的“酸诱导吸附”和“亲和强化吸引”原理、构建完全非对称冠囊泡的“胶束-囊泡转变法”、构建高级囊泡结构的“融合诱导粒子自组装”方法、可宏量制备囊泡的氨基酸环内酸酐开环聚合诱导自组装方法;后者主要介绍“以糖控糖”囊泡、治疗糖尿病溃疡囊泡、抗菌囊泡、抗癌囊泡、靶向治疗骨质疏松症囊泡和护肾血管造影囊泡.最后,对高分子囊泡的未来发展方向进行了展望.     

非均相膜聚合物囊泡的构筑、应用及展望

聚合物囊泡是通过聚合物自组装构筑的纳米组装体,由于其独特的空腔-膜层-冠层结构,在生物医用等领域具有较好的应用前景,因此越来越受到研究者的关注.不同于传统的均相膜囊泡,非均相膜囊泡的膜层由不相容的组分构成,呈现出微相分离的特点,具有丰富的功能.本文以近年来本课题组及国内外同行在非均相膜囊泡领域的研究成果为基础,详细论述了非均相膜囊泡的膜层结构、理论构筑与设计策略,讨论了其在生物大分子包载与递送、高效抗菌、癌症诊疗与糖尿病治疗、能源存储、水处理等领域的潜在应用,并对该领域的发展方向进行了展望.     

葡萄糖响应苯硼酸接枝壳聚糖盐酸盐抗肿瘤药物载体

通过分子改性向壳聚糖盐酸盐高分子链中引入苯硼酸基,合成了双亲性化合物苯硼酸接枝壳聚糖盐酸盐.细胞毒性实验表明苯硼酸接枝壳聚糖盐酸盐具有良好的细胞相容性.该双亲性化合物能够自组装成胶束聚集体,并包封疏水药物.以阿霉素为模型药物,研究了载药胶束聚集体的体外药物释放行为,结果表明,阿霉素在载药胶束聚集体内能够持续释放,且具有葡萄糖响应性.在生理p H=7.4和固体肿瘤弱酸性(p H=6.5)条件下,药物的释放速度十分缓慢,而当释放介质中有葡萄糖存在时,药物释放速度都明显加快.     

膜表面具有2-羟基-3-氯丙基或环氧丙基的对pH和离子强度敏感的新型磷酸酯囊泡

近年来,囊泡已被广泛应用于药物基因传导、人工模拟酶和纳米分子器件等研究领域,在对囊泡研究中,需要对囊泡进行某种包结或化学修饰,并对囊泡的稳定性及对物质的包结与释放进行可控操作．囊泡状态下使囊泡分子间聚合是提高囊泡稳定性的有效方法之一,苯乙烯等一些可进行聚合反应的基团已被导入囊泡中,我们曾在单长链烷基磷酸酯的亲水头部引入2-羟基3-氯丙基,进而将其转变成化学活性的环氧丙基.     

Equilibrium sorption properties of cholesterol surface-imprinted Se-containing polymeric sorbents synthesized by Pickering emulsion polymerization

The equilibrium sorption isotherms of cholesterol on surface-imprinted Se-containing sorbents based on 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate were studied. The equilibrium sorption of cholesterol occurred on a homogeneous sorption surface of the molecularly imprinted polymer (template content 6 mol.%). The sorption surface had a higher affinity to template molecules compared to the monolayer. An increase in the amount of template introduced during modification of the polymer matrix led to an increase in the sorption surface area of solvated polymers available for cholesterol binding.

     

Effects of Calcium Ions on Thermodynamic Properties of Mixed Bilirubin/Cholesterol Monolayers

The mixed monolayer behavior of bilirubin/cholesterol was studied through surface pressure-area (?-A) isotherms on aqueous solutions containing various concentrations of calcium ions. Based on the data of ?-A isotherms, the mean area per molecule, collapse pressure, surface compressibility modulus, excess molecular areas, free energy of mixing, and excess free energy of mixing of the monolayers on different subphases were calculated. The results show an expansion in the structure of the mixed monolayer with Ca2+ in subphase, and non-ideal mixing of the components at the air/water interface is observed with positive deviation from the additivity rule in the excess molecular areas. The miscibility between the components is weakened with the increase of concentration of Ca2+ in subphase. The facts indicate the presence of coordination between Ca2+ and the two components. The mixed monolayer, in which the molar ratio of bilirubin to cholesterol is 3:2, is more stable from a thermodynamic point of view on pure water. But the stable 3:2 stoichiometry complex is destroyed with the increase of the concentration of Ca2+ in subphase. Otherwise, the mixed monolayers have more thermodynamic stability at lower surface pressure on Ca2+ subphase.     

Ferroferric oxide/chitosan scaffolds with three-dimensional oriented structure

A facile approach to construct ferroferric oxide/chitosan composite scaffolds with three-dimensional oriented structure has been explored in this research.Chitosan and ferroferric oxide are co-precipitated by using an in situ precipitation method,and then lyophilized to get the composite scaffolds.XRD indicated that Fe₃O₄ was generated during the gel formation process,and increasing the content of magnetic particles could destruct the crystal structure of chitosan. When the content of magnetic particles is lower than 10%,the layer-by-layer structure and wheel spoke structure arc coexisting in the scaffolds.Increasing the content of magnetic particles,just layer-by-layer structure could be observed in the scaffolds.Ferroferric oxide particles were uniformly distributed in the matrix,the size of which was about 0.48μm in diameter,2μm in length.Porosity of magnetic chitosan composite scaffolds is about 90%.When the ratio of ferroferric oxide to chitosan is 5/100,the compressive strength of the material is 0.4367 MPa,which is much higher than that of pure chitosan scaffolds,indicating that the layer-by-layer and wheel spokes complex structure is beneficial for the improvement of the mechanical properties of chitosan scaffolds.However,increasing the content of ferroferric oxide,the compressive strength of scaffolds decreased,because of the decreasing of chitosan crystallization and aggregation of magnetic particles as stress centralized body.Another reason is that the layer-by-layer and wheel spokes complex structure makes bigger contributions for the compressive strength than the layer-by-layer structure does.Three-dimensional ferroferric oxide/chitosan scaffolds could be used as hyperthermia generator system,improving the local circulation of blood, promoting the aggradation of calcium salt and stimulating bone tissue regeneration.     

The structure of percolating lipid monolayers

The lattice structure and in plane molecular organization of Langmuir monolayer of amphiphilic material is usually determined from grazing incidence X-ray diffraction (GIXD) or neutron reflectivity. Here we present results of a different approach for determination of monolayer lattice structure based on application of fractal analysis and percolation theory in combination with Brewster angle microscopy. The considerations of compressibility modulus and fractal dimension dynamics provide information on percolation threshold and consequently by application of percolation theory on the lattice structure of a monolayer. We have applied this approach to determine the monolayer lattice structures of single chain and double chain lipids. The compressibility moduli were determined from measured π-A isotherms and fractal dimensions from corresponding BAM images. The monolayer lattice structures of stearic acid, 1-hexadecanol, DPPC and DPPA, obtained in this way conform to the corresponding lattice structures determined previously by other authors using GIXD.     

Preparation and characterization of temperature- and pH-sensitive hemicellulose-containing hydrogels

In this work, a hemicellulose-containing hydrogel was synthesized. As the first step, a temperature- and pH-sensitive copolymer was synthesized from itaconic acid and N-isopropylacrylamide (NIPAAm). Then the hydrogel was prepared by reacting the copolymer with acylated hemicellulose and polyvinyl alcohol. The morphology, compressive strength, thermal stability, swelling/deswelling behavior, drug-release behavior performances of the hydrogels were investigated. The lower critical solution temperature of the hydrogels varied in 34–44°C when the NIPAAm and itaconic acid mass ratios ranged in 100/0–90/10. Both temperature and pH had a significant influence on equilibrium swelling ratio of hydrogels. The equilibrium swelling ratio increased with pH, but decreased with temperature. Cytocompatibility assay demonstrated that this hemicellulose-containing hydrogel was biocompatible. The release process of salicylic acid suggested that this hydrogel had a potential use in controlled drug release.     

胆固醇/卵磷脂/壳聚糖体系中碳酸钙模拟生物矿化的研究

本文采用X射线衍射、红外光谱和扫描电子显微镜等方法研究了胆固醇／卵磷脂／壳聚糖体系中碳酸钙模拟生物矿化过程。通过改变有机基质的组成,使有机基质的模板作用 也发生改变,从而使生成方解在一重型里面在酸钙的模板可生成球霰石型的碳酸钙。文中还进一步探讨了体系中壳聚糖、卵磷脂、胆固醇三者的协同作用对生成碳酸钙晶型的影响。     

Application of Brewster angle microscopy and fractal analysis in investigations of compressibility of Langmuir monolayers

The aim of this study was to investigate the connection between the lipid/amphiphile monolayer structure at the interface and its macroscopic/rheological properties, in particular, to establish the link between the fractality of the monolayer structure and its compressibility modulus. To that purpose we have used fractal analysis of images obtained by Brewster angle microscopy to infer the fractal dimension of the monolayer structure and relate its change to the corresponding changes in compressibility derived from a simultaneously measured π-A isotherm. The results of the study confirmed the starting assumption based on theoretical considerations that the fractal dimension of an amphiphilic monolayer and its compressibility should be correlated. We have shown that there exists a strong correlation between the fractal dimension and the corresponding compressibility modulus of different amphiphilic materials. Thus, confirming the link between the short ordered structure on the molecular level and the macroscopic property-compressibility of the monolayer. The established correlation between the fractal dynamics and compressibility modulus of the monolayer enabled identification of onset of percolation-a second-order phase transition that is otherwise not easy and unambiguously detectable. We have found that the signature of percolation in a monolayer, regardless of its composition, is the occurrence of a sharp increase (a jump) of compressibility modulus (at macroscopic level) at the characteristic value of the corresponding fractal dimension D = 1.89. This is the result of the abrupt establishment of a connected structure on the molecular level, consequently involving a change in the elastic properties of the monolayer on a macroscopic scale. The results of this investigation provide means for unambiguous identification of the onset of percolation in the Langmuir layer and should facilitate a more efficient application of the percolation theory in further study of processes and structures at the interface during the monolayer compression.     

不同交联剂含量对戊二醛交联壳聚糖膜结构与性 能影响的研究

仔细研究壳聚糖膜的结晶度、溶胀度及其对二价铜离子的吸附量与交联剂戊二醛含量(特别是在戊二醛含量较低时)的关系。结果发现膜的结晶度、溶胀度以及对铜离子的吸附量均在戊二醛摩尔分数为0.25%时达到极大值。结晶度的增大可归结于轻度交联能使壳聚糖分子链在成膜时排列更为有序;而溶胀度和对铜离子吸附量的增加则可认为是交联能使壳聚糖中原先被氢键作用所束缚的氨基获得了自由。     

Synthesis and characterization of temperature-sensitive and biodegradable hydrogel based on N-isopropylacrylamide

Based on a biodegradable cross-linker, N-maleyl chitosan (N-MACH), a series of Poly(N-isopropylacrylamide) (PNIPAAm) and Poly(N-isopropylacrylamide-co-acrylamide) [P(NIPAAm-co-Am)] hydrogels were prepared, and their lower critical solution temperature (LCST), swelling kinetics, equilibrium swelling ratio in NaCl solution, and enzymatic degradation behavior in simulated gastric fluids (SGF) were discussed. The LCST did not change with different cross-linker contents. By altering the NIPAAm/Am molar ratio of P(NIPAAm-co-Am) hydrogels, the LCST could be increased to 39°C. The LCST of the hydrogel was significantly influenced by the monomer ratio of the NIPAAm/Am but not by the cross-linker content. In the swelling kinetics, all the dry hydrogels exhibited fast swelling behavior, and the swelling ratios were influenced by the cross-linker content and NIPAAm/Am molar ratios. Equilibrium swelling ratio of all the hydrogels decreased with increasing NaCl solution concentration. In enzymatic degradation tests, the weight loss of hydrogels was dependent on the cross-linker contents and the enzyme concentration.