【作者】 张欣；

【导师】 巴信武； 安朴英；

【作者基本信息】 河北大学 ， 高分子化学与物理， 2021， 硕士

【摘要】 过氧化氢（H₂O₂）作为细胞内活性氧的重要组成部分,参与了许多重要的生理病理活动,在诱导氧化应激反应、细胞信号传导、增殖和分化等方面起着重要作用。当患有肿瘤、糖尿病、动脉硬化等疾病时,人体内会产生过量的H₂O₂。因此,针对人体微环境中H₂O₂浓度水平的变化,研发对H₂O₂有刺激响应性和靶向性的药物载体具有重要的研究意义。微胶囊是一种核-壳结构的微型容器,具有渗透性高、稳定性好等优点。药物微胶囊能在不改变药物性质的前提下包裹药物,广泛应用于载药释放领域,可以实现药物的靶向传递,降低毒性,提高药物利用率。本文基于硼-碳键的H₂O₂敏感性,设计合成了具有H₂O₂刺激响应性的药物微胶囊,并详细研究了微胶囊的性能。主要研究内容如下:第一章:简要介绍了微胶囊和过氧化氢刺激响应性材料的研究进展,提出了本文的研究目的。第二章:利用反相乳液聚合法,以可压性淀粉和1,4-苯二硼酸为壁材,己酮可可碱为芯材,制备了交联淀粉-苯二硼酸药物微胶囊。探讨了复合乳化剂配比、乳化剂用量、乳化速度、乳化时间、芯壁比、壁材比、制备温度和反应时间等因素对微胶囊粒径大小及其分布和形貌的影响。采用红外光谱仪、Malvern激光粒度分析仪、扫描电子显微镜和透射电子显微镜表征了所制备的微胶囊的结构、粒径大小、粒径分布及形貌。确定了制备交联淀粉-苯二硼酸药物微胶囊的最佳条件。第三章:对交联淀粉-苯二硼酸药物微胶囊的包覆率、H₂O₂响应性药物释放行为以及主要因素影响的药物释放行为进行研究,采用紫外-可见分光光度计进行了表征。研究了微胶囊在不同H₂O₂浓度下的药物释放行为,证实了微胶囊具有明显的H₂O₂响应性,确定了微胶囊药物响应释放适宜的H₂O₂浓度为0.2 mmol/L。第四章:利用反相乳液聚合法,以聚乙烯醇（PVA）和1,4-苯二硼酸为壁材,己酮可可碱为芯材,制备了交联聚乙烯醇（PVA）-苯二硼酸药物微胶囊。研究了微胶囊在不同H₂O₂浓度下的释放行为,证实了微胶囊的H₂O₂响应性,确定了微胶囊药物响应释放适宜的H₂O₂浓度为1.0 mmol/L。系统研究了PVA浓度、乳化剂用量、乳化速度、乳化时间、芯壁比和壁材比等因素对微胶囊粒径大小及其分布、包覆率和形貌的影响。采用红外光谱仪、Malvern激光粒度分析仪、扫描电子显微镜、透射电子显微镜和紫外-可见分光光度计表征所制备的微胶囊的结构、粒径大小及其分布、形貌、包覆率及药物释放行为,确定了制备交联聚乙烯醇（PVA）-苯二硼酸药物微胶囊的最佳条件。更多还原

【Abstract】 As an important component of intracellular reactive oxygen species,hydrogen peroxide（H₂O₂）is involved in many important physiological and pathological activities,and plays an important role in inducing oxidative stress response,cell signal transduction,proliferation and differentiation.Excess H₂O₂ is produced in the body when people suffer from diseases such as cancer,diabetes and arteriosclerosis.Therefore,in view of the changes in the concentration of H₂O₂ in the human microenvironment,the development of drug carriers that are stimulus-responsive and targeted to H₂O₂ has important research significance.Microcapsule is a kind of microcontainer with core-shell structure,which has the advantages of high permeability and good stability.Drug microcapsules can encapsulate drugs without changing the properties of the drugs,and are widely used in the field of drug-loaded release,which can achieve targeted drug delivery,reduce toxicity,and improve drug utilization.In this paper,based on the H₂O₂sensitivity of boron-carbon bond,drug microcapsules with H₂O₂ stimulation response were designed and synthesized,and the performance of microcapsules was studied in detail.The main research contents are as follows:Chapter 1:This chapter briefly introduces the research progress of hydrogen peroxide stimulation-responsive materials and microcapsules,and proposes the research objectives of this paper.Chapter 2:The cross-linked starch-phenyldiboric acid drug microcapsule was prepared by reverse phase emulsion polymerization,using compressible starch and 1,4-phenyldiboric acid as wall materials and pentoxifylline as core materials.The effects of compound emulsifier ratio,emulsifier dosage,emulsifying speed,emulsifying time,core-wall ratio,wall-material ratio,reaction temperature and reaction time on the particle size,distribution and morphology of microcapsules were investigated.The structure,particle size,particle size distribution and morphology of the prepared microcapsules were characterized by infrared spectrometer,Malvern laser particle size analyzer,scanning electron microscope and transmission electron microscope.The optimum conditions for preparing crosslinked starch-phenyldiboric acid drug microcapsules were determined.Chapter 3:The coating rate of cross-linked starch-benzenediboronic acid drug microcapsules,the H₂O₂ responsive drug release performance and the drug release performance affected by the main factors were studied,and the UV-visible spectrophotometer was used for characterization.The drug release properties of the microcapsules under different H₂O₂concentrations was studied,and it was confirmed that the microcapsules had obvious H₂O₂responsiveness.It was determined that the appropriate H₂O₂ concentration for microcapsule drug release was 0.2mmol/L.Chapter 4:The cross-linked polyvinyl alcohol（PVA）-phenyldiboric acid drug microcapsules were prepared by reverse phase emulsion polymerization,using PVA and 1,4-phenyldiboric acid as wall materials and pentoxifylline as core materials.The release performance of the microcapsules under different H₂O₂ concentrations was studied,the H₂O₂responsiveness of the microcapsules was confirmed,and the appropriate H₂O₂ concentration for the release of the microcapsule drugs was determined to be 1.0 mmol/L.The influence of factors such as PVA concentration,emulsifier dosage,emulsification speed,emulsification time,core-to-wall ratio and wall-to-wall ratio on the particle size and distribution,coating rate and morphology of microcapsules was systematically studied.Infrared spectrometer,Malvern laser particle size analyzer,scanning electron microscope,transmission electron microscope and ultraviolet-visible spectrophotometer were used to characterize the structure,particle size and distribution,morphology,coating rate and drug release properties of the prepared microcapsules,The optimal conditions for preparing cross-linked polyvinyl alcohol（PVA）-benzenediboronic acid drug microcapsules were determined.更多还原