磷酸胆碱基细胞膜仿生界面的构建与研究

发布时间：2018-03-30 18:51

本文选题：磷酸胆碱　切入点：仿生　出处：《浙江大学》2005年博士论文

【摘要】：本论文针对生物材料的生物相容性这一关键科学问题,依据现代仿生学原理,以磷酸胆碱生物膜仿生为手段,分别开展了介入医用装置表面和纳米药物微载体界面的高生物相容性设计与研究: 以均匀稳定的、高血液相容性的药物控释介入支架为目标,采用由细胞膜仿生单体甲基丙烯酸磷酸胆碱酯(MPC)、疏水单体甲基丙烯酸十八酯(SMA)以及交联单体甲基丙烯酸羟丙酯(HPMA)和甲基丙烯酸三甲氧基硅丙酯(TSMA)四元复合,成功地制备了一种可交联磷酸胆碱细胞膜仿生医用涂层材料。采用浸涂(Dip-Coating)和热交联技术,利用此仿生材料获得了仿生涂层和带药仿生涂层。原子力显微镜、接触角和紫外光谱的测试结果表明,仿生涂层具有良好的稳定性;接触角测试的结果显示,当仿生涂层从空气环境变为水环境后,涂层的表面会经历一个表面自迁移重组的过程,最终获得了一个在水环境下,细胞膜仿生磷酸胆碱富集的仿生涂层表面。复钙化时间测试和血小板粘附实验表明,仿生涂层的引入能够显著提高材料的血液相容性。以Rhodamine S为模型药物,对仿生涂层的药物缓释行为进行的初步探索所得结果表明,药物的释放行为可以通过仿生涂层中的交联剂的含量进行有效的调节。稳定的、高血液相容性的药物涂层材料为带药支架设计提供了良好的物质基础。进一步复合和优化了浸涂、吹管和热交联技术,在具有复杂体型结构的冠脉支架表面获得了均匀的、稳定的、可长期释放雷帕霉素药物的仿生药物涂层。光学显微镜和激光共聚焦显微镜(CLSM)测试表明,(载药)仿生涂层能够被光滑、均匀的涂覆于支架表面;(载药)涂层在支架球囊扩张过程中不脱落、不开裂、具有良好的稳定性。雷帕霉素药物涂层的体外释放实验结果表明,冠脉支架的雷帕霉素药物涂层可维持长期、稳定、有效的药物释放。体外实验表明,仿生涂层可有效降低支架表面的血小板粘附。小动物(兔)和大动物(小型猪)实验结果均表明,这种均匀的、稳定的、高血液相容性的仿细胞膜载药涂层可长效释放雷帕霉素,有效降低再狭窄,为国产药物支架的产业化生产提供了有效的技术支撑。以具有优异的血液相容性和高稳定性的纳米药物载体为目标,本文通过MPC的原子转移自由基聚合(ATRP),得到了细胞膜仿生的两亲性分子CMPC。将
[Abstract]:Aiming at the key scientific problem of biocompatibility of biomaterials, according to the principle of modern bionics, the bionic method of choline phosphate biofilm is used in this paper. The design and study of high biocompatibility between the surface of interventional medical device and the interface of nano-drug microcarrier were carried out. The goal is a uniform, stable, highly compatible drug controlled release interventional stent. The composite was composed of the cell membrane bionic monomer choline methacrylate (MPC), the hydrophobic monomer octadecyl methacrylate (SMA) and the crosslinking monomer (hydroxypropyl methacrylate) and the trimethoxypropyl methacrylate (TSMA). A biomimetic medical coating material of crosslinked choline phosphate membrane was successfully prepared. The bionic coating and bionic coating with medicine were obtained by dip-Coatingand thermal crosslinking technology. Atomic force microscope (AFM) was used to prepare the biomimetic coating. The results of contact angle and UV spectra show that the bionic coating has good stability, and the contact angle test shows that when the bionic coating changes from air to water, The surface of the coating will undergo a process of surface self-migration and recombination. Finally, a bionic coating surface with membrane bionic choline phosphate enrichment in water environment is obtained. The multiple calcification time test and platelet adhesion test show that, The introduction of bionic coating can significantly improve the blood compatibility of the material. The preliminary study on the drug release behavior of the biomimetic coating using Rhodamine S as model drug shows that, The drug release behavior can be effectively regulated by the content of cross-linking agent in the bionic coating. The stable and high blood compatibility drug coating materials provide a good material basis for the design of drug-bearing scaffolds. Further recombination and optimization of dipping, blowing tube and thermal crosslinking techniques to obtain uniform and stable coronary stents with complex structures, Biomimetic coatings that release rapamycin over a long period of time. Optical and laser confocal microscopy (CLSM) tests show that the bionic coating can be smooth. The uniform coating on the surface of the stent does not fall off, does not crack, and has good stability during the balloon dilation of the stent. The results of in vitro release of rapamycin drug coating show that, Rapamycin drug coating on coronary stent can maintain long-term, stable and effective drug release. Bionic coating can effectively reduce platelet adhesion on the scaffold surface. The experimental results of small animals (rabbits) and large animals (small pigs) show that this kind of uniform, stable, The coating with high blood compatibility can release rapamycin for a long time and reduce restenosis effectively. It provides an effective technical support for the industrial production of domestic drug stents. Aiming at the excellent blood compatibility and high stability of nanopharmaceutical carriers, a biomimetic amphiphilic molecule of MPC was obtained by atom transfer radical polymerization of MPC.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R314

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