环境响应性嵌段共聚物的制备及其性能、应用研究

发布时间：2018-06-24 10:48

本文选题：两亲性嵌段共聚物 + 光响应型聚合物胶束　；参考：《湖南大学》2016年硕士论文

【摘要】：传统药物的口服及注射方式由于其局限性存在许多缺点,采用刺激响应性聚合物胶束作为药物载体,发挥其在体外稳定存在,体内能利用环境刺激来控制药物释放的优点,既能改善难溶性药物的吸收效率、实现药物的缓释控制,还能减小药物毒副作用、提高血液中药物浓度等。从而在生物医用领域具有良好的应用前景。在所有的环境响应类型中,光响应是一种应用比较广泛的外部刺激,具有洁净、无创、高效的特点。与其它刺激类型例如pH和氧化还原敏感型相比,光响应聚合物胶束的优势在于不需要特定的化学环境变化也能在特定的位置和时间快速的释放包裹药物,而这种化学环境的变化分为两种,一种是需要生物体自身能够提供的环境,例如癌症细胞环境呈弱酸性,这种情况下释放的可控性较低,而另外一种则需要通过外部调节来实现,这势必涉及到生物相容性、生物可降解性和生物毒性等问题,因此,光响应性聚合物胶束药物载体具有其他响应型药物载体不可比拟的优势。在文献调研的基础上,本文设计合成了两种环境响应型聚合物胶束,并对光响应型的聚合物胶束的药物可控释放进行了研究。我们将具有光响应性的螺吡喃结构引入聚合物的结构设计中,制备得到了具有光响应性和生物相容性的聚合物胶束药物载体。具体研究内容包括：合成了一种具有光响应性质的双键螺吡喃单体用于RAFT聚合,然后通过小分子RAFT试剂与生物相容性单体聚乙二醇单甲醚酯化得到PEG基大分子RAFT试剂,采用RAFT聚合法聚合双键螺吡喃得到具有光响应性的嵌段共聚物PEG113-b-PSPm。利用核磁共振氢谱(1H NMR)、核磁共振碳谱(13C NMR)和凝胶渗透色谱(GPC)对嵌段聚合物的分子结构进行表征。采用荧光探针法测试聚合物的临界胶束浓度(CMC)。通过扫描电镜(SEM)和动态激光光散射仪(DLS)检测共聚物在水溶液中的自组装行为。采用紫外可见光光谱对其紫外光响应性质进行表征,并通过SEM和DLS研究了其在紫外光照射下聚合物胶束的解离行为,同时,利用荧光发射光谱研究了聚合物胶束的模拟药物尼罗红在紫外光照射下的可控释放,并且采用细胞毒性测试(MTT)法评价聚合物胶束药物载体的生物学性能。本文还将具有温度响应性的NIPAAm单体引入到聚合物结构中,制备了一种具有温度响应性和生物相容性的聚合物胶束药物载体。具体研究内容包括：利用大分子RAFT试剂聚合NIPAAm单体,得到PEG113-b-PNIPAAmn温度响应性嵌段共聚物。利用’HNMR、13C NMR和GPC对嵌段聚合物的分子结构进行表征。利用紫外可见吸收光谱仪研究不同聚合度PEG113-b-PNIPAAmn的其温度响应特性。
[Abstract]:Because of its limitations, the traditional drug oral and injection methods have many disadvantages. The stimulus-responsive polymer micelles are used as drug carriers to give full play to their stable existence in vitro, and to control the release of drugs by environmental stimulation in vivo. It can not only improve the absorption efficiency of insoluble drugs, realize the control of drug release, but also reduce the side effects of drugs and increase the concentration of drugs in blood. So it has a good application prospect in the field of biomedicine. Among all kinds of environmental responses, light response is a widely used external stimulus with the characteristics of clean, non-invasive and efficient. Compared with other types of stimuli such as pH and redox sensitive, photoresponsive polymer micelles have the advantage of releasing encapsulated drugs at specific locations and times without requiring specific chemical environment changes. There are two types of changes in the chemical environment, one that requires the environment that organisms themselves can provide, such as the weak acidity of the cancer cell environment, in which the release is less controllable. The other one needs to be achieved through external regulation, which is bound to involve biocompatibility, biodegradability, biotoxicity and so on. Photoresponsive polymer micelle drug carriers have incomparable advantages over other responsive drug carriers. On the basis of literature review, two kinds of environmental responsive polymer micelles were designed and synthesized, and the drug controlled release of photoresponsive polymer micelles was studied. The photoresponsive spiropyran structure was introduced into the polymer structure design and the polymer micelle drug carriers with photoresponse and biocompatibility were prepared. The main contents are as follows: a double bond spiropyran monomer with photoresponse was synthesized for raft polymerization, and then the PEG-based macromolecule raft reagent was synthesized by esterification of small molecule raft reagent with biocompatible monomer polyethylene glycol monomethyl ether. Block copolymers PEG113-b-PSPmwith photoresponse were prepared by raft polymerization. The molecular structures of block polymers were characterized by 1H NMR, 13C NMR and GPC. The critical micelle concentration (CMC) of polymer was measured by fluorescence probe method. The self-assembly behavior of copolymers in aqueous solution was investigated by scanning electron microscopy (SEM) and dynamic laser light scattering (DLS). UV-Vis spectra were used to characterize the UV response of the polymer micelles, and the dissociation behavior of the polymer micelles under UV irradiation was studied by SEM and DLS. The controlled release of Nile red, a mimic drug of polymer micelles, was studied by fluorescence emission spectroscopy, and the biological properties of polymer micelle drug carriers were evaluated by cytotoxicity test (MTT). In addition, NIPAAm monomer with temperature response was introduced into the polymer structure to prepare a polymer micellar drug carrier with temperature response and biocompatibility. The main contents are as follows: PEG113-b-PNIPAAmn block copolymers were prepared by polymerization of NIPAAm monomer with macromolecular raft reagent. The molecular structure of block polymer was characterized by 13C NMR and GPC. The temperature response of PEG113-b-PNIPAAmn with different degree of polymerization was studied by UV-Vis absorption spectrometer.
【学位授予单位】：湖南大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O631;TQ460.4

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