对于负载天然活性成分的抗菌和抗利仕曼虫金属材料的合成与功能化研究

发布时间：2018-07-28 21:15

【摘要】：利什曼病,属于Ⅰ型疾病(目前是一种新兴的不可控疾病),还没有引起足够关注,因此该疾病在全球已经发展成为一个严峻的问题。而且,现有的药物是有限的且药物的副作用较大,此外,利什曼原虫已证明对这些药物具有普遍的耐药性。以上这些因素形成了控制寄生虫的障碍。其次,几种病原菌对大多数抗生素均有明显的耐药性。因此,一种不同于以往的治疗策略亟待开发,开发出具有更高效、安全(无毒)药物能够消灭致病微生物、抑制耐药性的蔓延与控制了利什曼病寄生虫和病原菌。其中,可以开发具有抗菌和抗利什曼病活性的纳米金属及功能化修饰的药物。这样的材料表现出具有广谱杀死微生物的活性。在本文的研究中,制备了金属纳米粒子材料(纳米金和纳米银)并负载了多种来源于植物的活性分子。这些活性分子具有双重功能:(i)减少重金属离子的使用,(ii)使药物具有长期稳定性。纳米金(AuNPs)和纳米银(AgNPs)药物制备后通过不同表征手段进行表征,如紫外-可见,傅里叶变换红外光谱,透射电子显微镜,X射线衍射和动态激光散射。研究部分——Ⅰ在这一课题研究中,制备纳米金/银颗粒与药物结合(来源于药用植物)。通过不同的条件优化(如:pH,温度,离子强度和浓度等)得到目标产物。这些纳米颗粒(纳米金/银)被应用于利什曼病和其他微生物致病菌。结果表明,制备得到的纳米金/银材料药物可以有效的抑制利什曼病致病菌等多种类似的致病菌的生长,在4.40到5.30μg/mL的浓度下。另外,这些纳米金/银材料药物可以有效的降低革兰氏阳性菌和革兰氏阴性菌的细菌耐药性。研究部分——Ⅱ项目Ⅱ的研究中主要包括纳米银药物制备,采用水提法得到板蓝根(中药材)的生物活性成分。通过两性霉素B (抗菌药)功能化修饰合成出纳米银。两性霉素B纳米药物和上述纳米颗粒作为抗利什曼病的药物。研究结果表明,采用光照射时(可见光)这些纳米粒子对杀死利什曼原虫的效果有所增强。辐照纳米银(88%的生长受到抑制)和两性霉素B纳米银(96%的生长受到抑制)表现出比未辐照样品的功效改善(73%的生长受到抑制)。我们的结论是,当光照射时大量的纳米银得到有效释放,从而产生了大量活性氧(ROS)。这些活性氧通过多种不同作用机制破坏细胞内寄生虫。研究部分——Ⅲ在这一部分的研究中,我们对纳米银的表面结构进行了修饰。首先,合成了具有生物相容性且带负电的纳米银颗粒,然后用生物高分子材料——壳聚糖(带正电)进行表面改性。带正电和负电的纳米银材料抗菌活性进行表征。我们观察到纳米颗粒的表面修饰对其生物活性起到重要的作用。纳米银通过壳聚糖修饰(带正电)能够提高药物活性与与带负电的银纳米颗粒相对比。纳米银可以通过静电作用“吸附”在目标细菌的细胞壁上,通过这一点可以提高带负电的纳米银的抗菌效果。因此可得出下面的结论,带正电的纳米银与带负电的纳米银相比更容易使细菌的细胞壁瓦解。另外,带正电的纳米银颗粒对比带负电的可以产生更多活性氧。从所有的实验中我们可以总结出,上述纳米银颗粒和细菌的表面化学性质对提高抗菌活性类的药物起到至关重要的作用。研究部分——Ⅳ在这一部分,我们报道了纳米金不同粒径大小对催化性能大小影响。实验变量的影响中,提取效率(天然产物提取)和盐前体优化由纳米金颗粒的粒径大小所决定。我们的数据显示,粒径的大小的改变可以影响纳米金的催化效果,小粒径的纳米金表现出更高的活性在减少亚甲蓝(一种危险的染料)和硝基酚(一种危险的化学试剂)变成一种有用的产物氨基酚。大约80%的亚甲蓝在80分钟内消失,在20nm的纳米金催化下(反应条件:pH=8, 30℃下可见光照射)。更重要的,动力学研究显示小粒径的纳米金与大粒径的纳米金相比更轻易的使硝基酚转变成氨基酚。实验结果可以得到这样的结论,纳米材料的表面积的改变对催化能力起到关键作用。
[Abstract]:Leishmaniasis, a disease of type I (currently a newly emerging uncontrollable disease), has not aroused enough attention, so the disease has become a serious problem worldwide. Moreover, existing drugs are limited and drug side effects are large. In addition, Leishman protozoa has proved to have universal resistance to these drugs. These factors form an obstacle to control the parasites. Secondly, several pathogens have obvious resistance to most antibiotics. Therefore, a different treatment strategy which is different from the past needs to be developed to develop a more efficient, safe (non-toxic) drug that can eliminate the pathogenic microorganism, inhibit the spread of drug resistance and control the leishmaniasis. Parasites and pathogenic bacteria. Among them, nano metal and functional modified drugs with antibacterial and antileishmaniasis activity can be developed. Such materials show the activity of broad-spectrum killing microorganisms. In this study, the metal nanoparticles (nanoscale and nano silver) are prepared and loaded with various sources of plant life. These active molecules have dual functions: (I) reducing the use of heavy metal ions, (II) the long-term stability of the drugs. The preparation of nanoscale gold (AuNPs) and nano silver (AgNPs) drugs is characterized by different characterizations, such as ultraviolet visible, Fu Liye transform infrared spectroscopy, transmission electron microscopy, X ray diffraction and dynamic lasers. Scattering. Study part I. in this study, the preparation of nanoscale gold / silver particles and drug binding (derived from medicinal plants). The target products were obtained by different conditions (such as pH, temperature, ionic strength and concentration). These nanoparticles (nanoscale / silver) were applied to leishmaniasis and other microbial pathogens. Nanoscale gold / silver materials prepared can effectively inhibit the growth of a variety of similar pathogenic bacteria, such as leishmaniasis pathogenic bacteria, at the concentration of 4.40 to 5.30 g/mL. In addition, these nano gold / silver materials can effectively reduce the bacterial resistance of gram-positive and gram negative bacteria. The biologically active ingredients of Radix Isatidis (Chinese herbal medicine) were obtained by water extraction. The nano silver was synthesized by functional modification of amphotericin B (antibacterials). Amphotericin B nanomaterials and these nanoparticles were used as anti Leishman drugs. Light) the effects of these nanoparticles on the killing of Leishmania were enhanced. Irradiated nano silver (growth inhibition of 88%) and amphotericin B nanossilver (inhibition of growth of 96%) showed a better effect than unirradiated samples (73% growth was inhibited). Our conclusion is that a large amount of nano silver is effectively released when light is irradiated. A large number of reactive oxygen species (ROS) are produced. These reactive oxygen species destroy the intracellular parasites through a variety of different mechanisms of action. Submaterials - chitosan (with positive electricity) surface modification. The antibacterial activity of nano silver materials with positive and negative electricity was characterized. We observed that the surface modification of nano particles played an important role in its biological activity. The nano silver modified by chitosan (with positive electricity) could raise the drug activity and the silver nanoparticles with negative electricity. By contrast, nano silver can "adsorb" on the cell wall of the target bacteria by electrostatic action, which can increase the antibacterial effect of nano silver with negative electricity. Therefore, the following conclusion can be drawn that the positive nano silver is more easily disintegrated from the cell wall of bacteria compared with the negative electrically charged nano silver. We can conclude from all experiments that the surface chemical properties of the nanoparticles and bacteria play an important role in improving the antiseptic drugs. Our data show that the size of the particle size can affect the catalytic effect of nanoscale gold. The smaller size of gold nanoparticles show a higher activity in the reduction of methylene blue (a dangerous dye). ) and nitrophenol, a dangerous chemical reagent, became a useful product of aminophenol. About 80% of methylene blue disappeared in 80 minutes, under the catalysis of 20nm nanoscale (reaction conditions: pH=8, visible light at 30 C). More important, the kinetic study showed that the small size of gold nanoparticles was more easily made by the nanoscale than the large particle size. The conversion of phenol to aminophenol can be concluded that the change of surface area of nanomaterials plays a key role in catalytic activity.
【学位授予单位】：北京化工大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R943;TB383.1

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