【作者】 高博；

【导师】 薛巍；

【作者基本信息】 暨南大学 ， 材料物理与化学， 2019， 硕士

【摘要】 多巴胺（DA）是一种典型的含儿茶酚的单体,具有多功能性,在碱性环境或氧化剂存在的条件下容易发生氧化自聚合反应,生成聚多巴胺（PDA）。通过控制反应条件,DA可在多种材料表面沉积成PDA涂层,也可以氧化-自组装成PDA微球（PDA Ps）。海藻酸钠（ALG）等天然阴离子多糖水凝胶很难实现高载药能力,因为凝胶网络吸附药物的能力很弱。采用传统离子交联的水凝胶易在生理盐水中快速溶胀而导致药物的暴释。本文系统地研究了引发条件对DA氧化自聚合反应及其产物成球性能的影响,利用DA/PDA组分对海藻酸钠进行改性,优化成胶与药物吸附性能。本论文具体的研究内容主要分为以下两个方面:1、多巴胺的氧化自聚合反应及其微球产物的制备我们系统地比较了氨水（碱性）与高碘酸钠（酸性）引发条件下,多巴胺氧化反应的特点;重点研究了高碘酸钠引发体系中,反应介质、单体与引发剂的浓度、反应时间等因素对氧化产物组成及其自组装过程的影响。利用紫外-可见光分光光度计（UV-Vis）、傅里叶红外光谱仪（FT-IR）、扫描电镜（SEM）、透射电镜（TEM）和纳米激光粒度仪（DLS）表征产物的化学组成与显微形貌,并基于此对氧化自聚合反应的机理进行了合理推测。载药和体外释放实验表明,PDA Ps对加替沙星（GFLX）具有良好的吸附能力并具有一定的缓释性能。体外细胞毒性实验表明,低浓度PDA Ps具有较好的生物相容性,这为其在生物医学相关领域的应用提供了一定的参考价值。2、多巴胺/聚多巴胺改性藻酸钠水凝胶的制备与表征及其对GFLX的体外释放研究在本论文中,用物理共混和化学共聚的方法制备多巴胺改性的藻酸钠水凝胶:（1）预先制备形貌均一的PDA Ps并分散到海藻酸钠溶液中,通过Ca²⁺交联,制备了一种PDA颗粒嵌入式水凝胶（ALG-PDA）。（2）氨水溶液（AS）或高碘酸钠（SP）用于引发ALG溶液中的DA反应,再进一步通过Ca²⁺交联,分别制得掺入DA/PDA组分的ALG-DA-AS和ALG-DA-SP两种水凝胶。通过UV-Vis、SEM、¹H NMR和FT-IR来表征掺入的DA/PDA组分在水凝胶中的化学组成与显微形貌。通过流变学测试,可以确定ALG-DA-SP水凝胶的溶胶-凝胶转变时间。在以加替沙星（GFLX）作为模型药物的载药和体外释放实验中,三种改性水凝胶与普通ALG水凝胶相比,均具有更高的载药能力和更慢的释放速度。体外细胞毒性实验表明,ALG、ALG-DA-AS和ALG-DA-SP三组水凝胶均具有相对较低的细胞毒性。溶胀实验表明,ALG-DA-SP水凝胶由于其共价交联结构,在生理盐水中浸泡72 h仍能保持完整的结构。本论文系统地表征了DA/PDA组份在凝胶网络中的存在形式,并阐述了其对凝胶形成与结构稳定性、药物吸附性能的影响。这为我们开发用于医疗和制药应用的原位形成水凝胶提供了一种新的策略。更多还原

【Abstract】 Dopamine（DA）is a typical catechol-containing monomer with multiple functions.It is prone to oxidative self-polymerization in the presence of an alkaline environment or an oxidizing agent to form polydopamine（PDA）.By controlling the reaction conditions,DA can be deposited as a PDA coating on a variety of materials or oxidized-self-assembled into PDA microspheres（PDA Ps）.Natural anionic polysaccharide hydrogels such as sodium alginate（ALG）are difficult to achieve high drug loading capacity,because the ability of gel network to adsorb drug is weak.Traditional ionic crosslinked hydrogels tend to swell rapidly in normal saline and resulting in drug burst.In this paper,the effects of initiator conditions on DA oxidation self-polymerization and its sphericity were studied systematically.The sodium alginate was modified by DA/PDA components to optimize the gelation and drug adsorption properties.The specific research content of this paper is mainly divided into the following two parts:1.Methods to control oxidation reaction of DA and prepare PDA nanoparticlesWe systematically compared the characteristics of dopamine oxidation reaction under the conditions of ammonia（basic）and sodium periodate（acidic）.The sodium periodate initiation system was studied in detail,and the effects of reaction medium,concentration of monomer and initiator,reaction time and other factors on the composition of oxidation products and their self-assembly process were studied.The chemical composition and morphology of the products were characterized by ultraviolet-visible spectrophotometer（UV-Vis）,fourier transform infrared spectroscopy（FT-IR）,scanning electron microscopy（SEM）,transmission electron microscopy（TEM）and nanometer laser particle size analyzer（DLS）.Based on this,a reasonable speculation on the mechanism of oxidation self-polymerization was carried out.Drug loading and in vitro release experiments showed that PDA Ps had good adsorption capacity for gatifloxacin（GFLX）and had a certain sustained release performance.In vitro cytotoxicity test showed that low concentration PDA Ps had good biocompatibility.In vitro cytotoxicity experiments showed that low concentrations of PDA Ps have good biological compatibility,which provides a certain reference for its application in biomedical related fields.2.Preparation and characterization of dopamine/polydopamine modified alginate gel and its release to GFLX in vitroIn this experiment,dopamine-modified alginate hydrogels were prepared by physical blending and chemical copolymerization:（1）PDA particle-embedded hydrogel（ALG-PDA）was prepared by pre-preparing uniformly dispersed PDA Ps and dispersing into sodium alginate solution through Ca²⁺cross-linking.（2）Ammonia aqueous solution（AS）or sodium periodate（SP）was used to initiate DA reaction in the ALG solution,and then two hydrogels incorporated DA/PDA components,ALG-DA-AS and ALG-DA-SP,were prepared respectively by further crosslinking through Ca²⁺.The chemical composition and microstructure of the incorporated DA/PDA component in the hydrogel were characterized by UV-Vis,SEM,nuclear magnetic resonance（¹H NMR）and FT-IR.The sol-gel transition time of ALG-DA-SP hydrogel was determined by rheology characterizations.In the drug-loading and in vitro release experiments using gatifloxacin（GFLX）as a model drug,the three modified hydrogels have higher drug loading capacity and slower release rate than the pristine ALG hydrogel.In vitro cytotoxicity tests showed that the three hydrogels of ALG,ALG-DA-AS and ALG-DA-SP had relatively low cytotoxicity.The swelling experiments showed that ALG-DA-SP hydrogel could maintain its complete structure after 72 hours immersion in normal saline due to its covalent cross-linking structure.In this experiment,the exact statuses of incorporated DA/PDA components in hydrogel matrix and their contributions to gel formation,structure and performance as drug carriers was systematically characterized.This provides a new strategy for the development of in situ hydrogels for medical and pharmaceutical applications.更多还原