聚乙二醇改性壳聚糖作为小分子药物载体的研究进展

壳聚糖具有抗菌、抗氧化、增强胶凝特性以及可作为生物活性分子的微型或纳米载体等优点,其化学改性和应用近年来受到广泛关注。然而,壳聚糖既不溶于有机溶剂也不溶于水,极大地限制了它的应用。在改性的壳聚糖中,聚乙二醇化壳聚糖不仅能保持壳聚糖的优点,还能提高水溶性,并能有效运输生物活性分子。本文综述了近5年间聚乙二醇化壳聚糖作为紫杉醇、阿霉素、5-氟尿嘧啶等小分子载体的研究进展,为今后的研究提供有益参考和理论依据。     

多功能水溶性聚合物配体制备纳米颗粒*

以多功能水溶性聚合物配体制备的纳米颗粒具有小尺寸、单分散、生物相容性良好的特点,同时还具备近红外荧光、超顺磁性等特殊物理性质,弥补了传统方法制备纳米颗粒的缺陷。本文综述了近年来多功能水溶性聚合物配体制备贵金属纳米颗粒、磁性纳米颗粒、纳米量子点以及复合结构纳米颗粒的进展;阐述了多功能水溶性聚合物配体在制备纳米颗粒方面的优势;分析了多功能水溶性聚合物的结构、分子量、浓度等因素对制备纳米颗粒的影响。最后,探讨了小尺寸、单分散、水溶性的纳米颗粒在配体交换、药物靶向传输体系、疾病检测、生物标签、核磁共振成像以及光电学等领域的应用,并展望了多功能水溶性聚合物配体制备纳米颗粒的研究方向。     

聚乙二醇改性壳聚糖作为小分子药物载体的研究进展

壳聚糖具有抗菌、抗氧化、增强胶凝特性以及可作为生物活性分子的微型或纳米载体等优点,因此其化学改性和应用近年来受到广泛关注。然而,壳聚糖既不溶于有机溶剂也不溶于水,极大地限制了它的应用。在改性的壳聚糖中,聚乙二醇化壳聚糖不仅能保持壳聚糖的优点,还能提高水溶性,并能有效运输生物活性分子。因此,本文总结了2008-2012年聚乙二醇化壳聚糖作为紫杉醇、阿霉素、5-氟尿嘧啶等小分子载体的最新进展,为今后聚乙二醇化壳聚糖的研究提供有益参考和理论依据。     

壳聚糖及其衍生物抗菌活性的研究进展

壳聚糖是自然界目前发现的唯一碱性多糖,具有自然来源丰富,生物相容性好,可被生物降解,安全无毒和抗菌性强等许多天然的优良特性,现其广谱抗菌性已得到广泛的认可,但较差的水溶性限制了它的进一步应用。因此,通过一定的改性方法制备壳聚糖衍生物以提高其水溶性,是目前壳聚糖研究方面的热点之一。本论文就近年来几种常见的壳聚糖亲水改性方法及其衍生物在抗菌方面的应用进展进行综述,以期对壳聚糖的深入研究提供参考。     

影响聚乙二醇-g-壳聚糖载药体系的一些因素北大核心CSCD

聚乙二醇-g-壳聚糖可以作为抗肿瘤药物、基因、多肽等多种生物大分子的载体,是一种优良的药物载体。聚乙二醇接枝壳聚糖可以改善壳聚糖的水溶性,保护聚乙二醇-g-壳聚糖纳米不被网状内皮系统(RES系统)识别和清除,促进纳米粒子在体内的长循环,将药物更有效地靶向目标组织。目前,聚乙二醇-g-壳聚糖作为药物载体在生物医药领域发挥着重要作用,本文就聚乙二醇-g-壳聚糖的特点,以及在机体的靶向性、缓释等提高药物疗效的关键因素做一论述。     

纳米氧化铈的抗氧化生物应用

CeO2是一种常见的催化材料,具有很高的实用及研究价值．人们在其形貌的可控合成以及催化活性的调节等方面进行了大量的研究,取得了很多成果．近年来,随着纳米材料生物应用研究的兴起,纳米氧化铈在生物抗氧化领域的应用受到了越来越多的关注．在纳米尺度下,由于表面氧缺陷的产生,氧化铈中部分cd4＋被还原为Ce3＋以稳定缺陷．此时材料中的Ce3＋和Ce^4＋能够可逆的转化,这一性质使得纳米CeO2能够催化分解生物体内的过量自由基,从而为治疗氧化应激类疾病提供了一种可能．本综述对纳米CeO2的生物抗氧化作用进行了总结,重点讨论了CeO2纳米颗粒的抗氧化机理以及影响其生物效应的关键因素,还介绍了纳米CeO2生物安全性相关的一些研究,并对其生物应用前景进行了展望．     

小尺寸低聚壳聚糖/丹参酮ⅡA纳米载药体系

正纳米载药系统以其独特的化学性质已广泛应用于小分子药物转运,并已有相关的临床实例报道[1~6].壳聚糖(CS)因其所特有的无生物毒性、易生物降解和良好生物相容性等优点而备受关注[7~16].由于传统方法制备的壳聚糖纳米颗粒粒径高达数百纳米,使其生物利用度低,限制了其更广泛应用.我们在前期工作中发现:一种无残留合成方法可以制备粒径在50~80 nm的小尺寸低聚壳聚     

纳米富勒烯(nC60)的生态毒性效应

随着纳米技术的飞速发展,纳米材料的应用日趋广泛.同时,纳米材料的大规模生产和应用对人体健康与生态环境可能产生的安全风险也引起了人们的普遍关注.富勒烯是应用最广泛的纳米材料之一,在水中能形成稳定的水溶性纳米颗粒,进而增大其在环境中的迁移性与生物暴露几率.然而目前对纳米富勒烯(nC60)的环境和毒性效应还知之甚少.本文综合评述了水溶性nC60纳米颗粒的制备、稳定机制、在环境中的迁移特性及其与环境中污染物的相互作用,并着重阐述了nC60可能产生的生物毒性效应.分析表明,nC60的生物毒性效应主要与nC60的表面化学特性和颗粒大小有关,同时环境介质也影响nC60的毒性.最后讨论了nC60生态环境效应研究中应加强的若干方面.     

光致活性氧淬灭方法检测生物抗氧化剂动力学模型分析

以TiO2纳米颗粒光催化反应为模型,研究了反应过程中的活性氧( ROS)产生以及活性氧淬灭的反应动力学模型。对苯二甲酸分子与体系中的光催化反应产生的OH·反应,生成具有荧光性质的2-羟基对苯二甲酸( lex=315 nm,lem=425 nm),因此对苯二甲酸作为氧化探针分子与体系中的生物抗氧化剂( AOs)分子竞争与ROS的反应,根据体系的荧光、反应时间以及AOs的浓度建立了AOs淬灭ROS的反应动力学模型。根据此模型推导AOs清除ROS的动力学常数,发现常见的生物抗氧化剂的抗氧化活性大小顺序为：硫辛酸、没食子酸、谷胱甘肽、尿酸、维生素C、维生素E、水溶性维生素E和胆红素。     

贵金属纳米颗粒的微生物合成

金属纳米颗粒在材料、催化、医学、环境等众多领域应用广泛,其中,金、银、铂、钯等贵金属的纳米颗粒作为良好的催化剂可提高反应的速率,因此,贵金属纳米颗粒的合成吸引了众多研究者的关注。传统的物理化学法虽能高效、可控地合成贵金属纳米颗粒,但是合成条件苛刻、成本昂贵、且会产生对环境有害的化学物质。因此,探索节能、环保、可持续的绿色合成方法成为纳米合成研究的热点之一。贵金属纳米颗粒的微生物合成法具备绿色合成技术的诸多要素,研究表明某些微生物能将金属盐转化成纳米材料,且微生物繁殖速度快、培养成本低、生长条件温和,从而得到了研究者们的广泛关注。本文归纳总结了目前微生物合成贵金属纳米颗粒的主要研究进展,包括贵金属纳米颗粒可能的合成机制以及尺寸与形貌控制方法,探讨了其在医学、催化、生物传感、环境方面的具体应用,并对贵金属纳米颗粒微生物合成的未来发展进行了展望。     

Influence of hydroxypropyl-β-cyclodextrin on the photostability and antiradical activity of Trolox

Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a derivative of vitamin E, can undergo photolysis upon UV irradiation. In the present study the photodegradation kinetics of Trolox were thus investigated in different systems in the absence and in the presence of titanium dioxide, a physical sunscreen present in several cosmetic products, that can act as photocatalyst. In all the considered media Trolox degraded under UVB light following pseudo-zero order kinetics, probably by a mechanism of photooxidation. The rate of Trolox photodegradation was lower in O/W emulsions than in aqueous solution and in gel; furthermore it was significantly influenced by the presence of TiO₂. Aiming to increase Trolox stability, it was complexed with hydroxypropyl-β-cyclodextrin: the inclusion complex was characterized by phase solubility studies, spectrophotometry and differential scanning calorimetry. The irradiation experiments indicated that complexation with hydroxypropyl-β-cyclodextrin was effective in reducing the photodegradation rate of Trolox. Moreover the host molecule favored the uptake of Trolox into the porcine skin, as shown by in vitro permeation studies. Nevertheless the assay of peroxidation, based on the reaction of malondialdehyde with thiobarbituric acid, indicated that the antioxidant activity of Trolox was maintained even after inclusion in cyclodextrin.     

On the complexation of Trolox with methyl-β-cyclodextrin: characterization, molecular modelling and photostabilizing properties

Exposure to UV radiations could reduce the efficiency of some antioxidants like Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a water-soluble vitamin E analogue largely employed in cosmetic products. Accordingly, in this paper we examined the possibility of increasing the stability of Trolox towards UVB irradiation by its complexation with methyl-β-cyclodextrin. Formation of the inclusion complex was confirmed by solubility diagrams, differential scanning calorimetry (DSC), and diffusion study through hydrophilic membrane. The stability constants and docking results suggested that the complexation phenomenon was related to the pH of the medium. The photodegradation studies were carried out in different topical formulations (gel, O/W emulsion, and W/O/W emulsion) containing Trolox free or complexed with methyl-β-cyclodextrin. Results showed that in all the cases Trolox degraded following pseudo-zero order kinetics. Moreover, the host molecule increased Trolox photostability also in the presence of TiO₂, a physical sunscreen well-known as photocatalyzer.     

Dissolution kinetics of oxidic nanoparticles: The observation of an unusual behaviour

The solubility of nanoparticles was measured in aqueous solution as a function of time, and oxides of aluminium, silicon, titanium, and zirconium were investigated. Our solubility results show a maximum at the beginning of the dissolution process, whereas over time, the solubility levels are shown to decrease. Depending on the special conditions the solubility maximum may exceed the long-time solubility of the nanoparticles by several orders of magnitude. This behaviour is called as kinetic size effect. The extent of the effect depends on the size, surface tension and mass of the particles exposed to dissolution. It will always be of practical interest if a larger quantity of nanoparticles is brought into contact with a solvent, even when the equilibrium solubility data appears negligible. A rigorous thermodynamic and kinetic analysis of a colloidal system, which includes nucleation, particle growth, Ostwald ripening, and dissolution of particles, shows at least a qualitative agreement between all the experimental results and model calculations.     

Solubility of gold nanoparticles as a function of ligand shell and alkane solvent

The solubility of ca. 5.0 nm gold nanoparticles was studied systematically as a function of ligand shell and solvent. The ligands were octane-, decane-, dodecane- and hexadecanethiols; the solvents were the n-alkanes from hexane to hexadecane and toluene. Supernatant concentrations in equilibrium with precipitated superclusters of nanoparticles were measured at room temperature (23 °C) with UV-Vis spectrophotometry. The solubility of nanoparticles ligated with decane- and dodecanethiol was greatest in n-decane and n-dodecane, respectively. In contrast, the solubility of nanoparticles ligated with octane- and hexadecanethiol showed decreasing solubility with increasing solvent chain length. In addition the solubility of the octanethiol ligated system showed a nonmonotonic solvent carbon number functionality with even numbered solvents being better solvents than neighboring odd numbered solvents.     

聚合物保护贵金属纳米粒子的相转移技术

依据聚乙烯吡咯烷酮(PVP)在水中的溶解度随温度升高而降低的特性,建立了将PVP保护的金、银、铂纳米粒子从水相转移到油相的简单而有效的相转移技术.方法是利用电化学还原法先于水溶液中制备粒度均匀的金属纳米粒子,然后向电化学合成后的金属纳米水溶胶中加入适量正丁醇,在搅拌条件下升温至80℃即可使金属纳米粒子从水相转移至有机相.纳米粒子的相转移效率很高,而且相转移后粒子在油相中分散很好,没有团聚现象发生.在此基础上进一步建立在油水混合体系电化学合成金属纳米粒子的实验方法,为收集纳米粒子和制备纳米粒子薄膜提供了新的有效途径.     

Nanosized paclitaxel particles from supercritical carbon dioxide processing and their biological evaluation

The rapid expansion of a supercritical solution into a liquid solvent (RESOLV) technique with benign supercritical carbon dioxide was applied to obtain aqueous suspended nanoparticles of the highly potent anticancer drug paclitaxel. The paclitaxel nanoparticles were protected from agglomeration by using a known nontoxic stabilization agent. The aqueous suspended paclitaxel nanoparticles of different average particle sizes were evaluated in vitro against human breast cancer cells. The results suggest that the nanosized paclitaxel particles are effective, with an antineoplastic activity comparable to that of the commercial paclitaxel formulation. The technique should be generally applicable to the processing of nanoparticles from other important drugs with aqueous solubility problems.     

反胶束法合成CdS纳米粒子及其表征

以AOT为保护剂,采用反胶束法合成CdS纳米粒子。利用水洗法洗去保护剂AOT,通过加入不同量的无水乙醇调节分散介质的极性,改变CdS纳米粒子在分散介质中的"溶解度",从而实现不同尺寸粒子的分离。采用紫外-可见(UV-vis)吸收光谱、透射电子显微镜(TEM)、荧光光谱法对其进行表征。     

Reduction of polymer surface tension by crystallized polymer nanoparticles

Self-consistent field theory is applied to investigate the effects of crystallized polymer nanoparticles on polymer surface tension. It is predicted that the nanoparticles locate preferentially at the polymer surface and significantly reduce the surface tension, in agreement with experiment. In addition to the reduction of surface tension, the width of the polymer surface is found to narrow. The reduced width and surface tension are due to the smaller spatial extent of the nanoparticles compared to the polymer. This allows the interface to become less diffuse and so reduces the energies of interaction at the surface, which lowers the surface tension. The solubility of the surrounding solvent phase into the polymer melt is mostly unchanged, a very slight decrease being detectable. The solubility is constant because away from the interface, the system is homogeneous and the replacement of polymer with nanoparticles has little effect.     

One-phase synthesis of gold nanoparticles with varied solubility

We developed a straightforward synthesis of gold nanoparticles with diameters in the range 2.1-7.0 nm which display solubility in both aqueous and nonpolar (toluene, chloroform) media. This versatile solubility of the nanoparticles is achieved by the use of a thiolated PEG capping agent. Their plasmon resonance band is virtually unaltered in different media.     

Nanoparticles on the basis of highly functionalized dextrans

New nanoparticles based on well-defined dextran esters were prepared by a dialysis process. Dextran was converted into a propionate with a degree of substitution of 1.70 and, subsequently, acylated under homogeneous reaction conditions with a pyroglutamic acid imidazolide, which is prepared in situ by conversion of pyroglutamic acid with N,N-carbonyldiimidazole. The synthesis path allows perfect control of the amphiphilicity and solubility. The highly functionalized polysaccharide derivative avoids the collapse of the nanostructure due to the prevention of hydrogen bond formation. The major fraction of the dextran propionate pyroglutamate nanoparticles investigated by SEM and AFM exhibits narrow size distribution with 370 nm as mean diameter and uniform spherical shape. The SEM image verifies that polymeric nanoparticles in the suspensions did not undergo any morphological changes within 3 weeks.