石墨烯及环糊精在自组装多层膜中缓释作用研究

发布时间：2018-04-30 23:31

本文选题：自组装 + 氧化石墨烯　；参考：《中国地质大学(北京)》2017年硕士论文

【摘要】：在生物医药材料中,药物分子的负载总量与缓释速率是决定材料功能与治疗效果的关键。高分子在制备给药薄膜、修饰医学植入物或纳米粒子药物载体表面等方面具有重要应用。目前在调节小分子药物缓释速率方面,使其达到持久可控匀速释放并且实现具有分子选择性的释放速率调节,以及对多种药物的释放速率分别加以调节,是缓释材料设计的难点,还没有成熟的解决方案。本文针对以上缓释材料设计中的难点,将石墨烯的多层结构与环糊精主客体作用引入层层组装缓释薄膜中,实现了对小分子的持久缓释,以及对多肽释放速率选择性调节,并在此基础上探索了能够分别调节多种药物缓释速率薄膜的设计与制备。首先,制备了共价交联的聚丙烯胺/氧化石墨烯(PAH/GO)自支撑多层膜,利用石墨烯片层在多层膜中的组装结构实现了对分子扩散的尺寸调控。尺寸1 nm左右的小分子亚甲基蓝、罗丹明、荧光素钠等可以通过薄膜,而多肽及蛋白质等大分子则不能通过。石墨烯组装的层数可以调节小分子的透过速率。利用制备的薄膜实现了小分子长达9天的匀速释放。将环糊精(CD)引入层层组装多层膜,利用环糊精主客体快速可逆的组装行为,选择性地调节了多肽的负载和缓释。主客体结合增加分子的负载效率,减慢扩散速率。利用数值模拟对层层组装膜中主客体结合作用对缓释行为的影响进行了定量分析。在此基础上,利用多层膜同时负载了阿霉素与带有金刚烷客体官能团的RGD多肽并分别调节了其扩散曲线。在缓释多层膜上,肺癌细胞与肺健康细胞的对比培养表明,通过对两种药物负载量及流速的分别调节,可以扩大肿瘤与健康细胞的差异性响应,达到让肿瘤细胞存活率低、健康细胞相对存活率高的效果。最后,将石墨烯组装结构与超分子主客体作用同时引入多层膜的结构中,结合具有高效负载能力的介孔二氧化硅粒子(MP-SiO2)制备了具有复合结构特征的(PAH/MP-SiO2)a-(PAH/GO)m-(PAH/PAA-CD)n多层膜。小分子亚甲基蓝负载在介孔二氧化硅中,石墨烯结构调节其缓释速率;带有金刚烷的多肽吸附在PAA-CD中,由主客体作用调节其释放速率,实现了对两种分子的缓释速率的差异性调节。
[Abstract]:In biomedical materials, the loading amount and slow release rate of drug molecules are the key factors to determine the material function and therapeutic effect. Polymer has important applications in preparation of drug delivery films, modification of medical implants or nanoparticles on the surface of drug carriers. At present, in regulating the slow release rate of small molecular drugs, they are able to achieve a sustained, controllable and uniform release rate and to achieve a molecular selective release rate regulation, as well as to regulate the release rates of various drugs separately. Is a slow release material design difficulties, there is no mature solution. In view of the difficulties in the design of sustained-release materials mentioned above, the multilayer structure of graphene and the host and guest interaction of cyclodextrin were introduced into the layer-by-layer assembled sustained-release films to realize the sustained release of small molecules and the selective regulation of the release rate of peptides. On the basis of this, the design and preparation of multidrug sustained release rate films were explored. Firstly, the self-supporting multilayer films of polyacrylamide / graphene oxide (PAH / GOA) were prepared, and the size of the molecular diffusion was controlled by the assembly structure of graphene in the multilayer. Small molecules, such as methylene blue, rhodamine and sodium fluorescein, which are about 1 nm in size, can pass through the film, while macromolecules such as peptides and proteins cannot pass through the film. The number of layers assembled by graphene can adjust the transmission rate of small molecules. The thin films were used to realize the uniform release of small molecules for up to 9 days. Cyclodextrin (CD) was introduced into the multilayer membrane, and the loading and sustained release of polypeptide were adjusted selectively by using the fast reversible assembly behavior of the host and guest of cyclodextrin. The combination of host and guest increases the loading efficiency of molecules and slows down the diffusion rate. The effects of host and guest binding on slow release behavior in laminated monolayers were quantitatively analyzed by numerical simulation. On this basis, RGD polypeptides with adriamycin and adriamycin guest groups were loaded and their diffusion curves were adjusted respectively. The comparative culture of lung cancer cells and lung healthy cells on the sustained release multilayer membrane showed that by adjusting the load and flow rate of two drugs separately, the differential response of tumor and healthy cells could be expanded, and the survival rate of tumor cells was low. The effect of high relative survival rate of healthy cells. Finally, the graphene assembly structure and supramolecular host and guest interaction were introduced into the multilayer structure at the same time, and combined with the mesoporous silica particle MP-SiO2 with high loading capacity, the multilayer films of PAH / MP-SiO2 / PAA-CDn were prepared with the composite structure characteristics of PAH / MP-SiO2 / PAH- / GOH- / PAA-CDn. In mesoporous silica, the structure of graphene regulates the slow release rate of graphene, and the peptide with adamantane is adsorbed in PAA-CD, and the release rate is regulated by host and guest action. The differential regulation of the slow release rate of the two molecules was realized.
【学位授予单位】：中国地质大学(北京)
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.2;TQ460.1

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