【作者】 徐敏；

【导师】 赵炯心；

【作者基本信息】 东华大学 ， 材料加工工程， 2013， 硕士

【摘要】 近儿十年来支架在医疗行业应用日益广泛,与此同时,支架表面的药物涂层也越来越受重视。通常,如果只是简单地把药物涂覆于支架的表面,这些药物在支架表面的半衰期很短,导致药物作用时间短,利用率低,毒副作用大。而将药物和可降解高聚物溶解在共同的有机溶剂中,再涂覆于支架表面,形成药物-可降解高聚物缓释涂层,则可以大大延长药物的半衰期。通过去溶剂化法来制备水分散聚己内酯载雷帕霉素纳米微球和水分散聚己内酯载紫杉醇纳米微球。传统的乳化溶剂挥发法制得的载药纳米微球通常具有疏水的表面,不能稳定存在于水相中。本文提供的载药纳米微球的制备方法,解决了由可生物降解聚合物或无规共聚物制备具有稳定亲水表层的载药纳米微球的问题。所制备的载雷帕霉素和紫杉醇的聚已内酯纳米微球在水中能够稳定存在,因而可用此纳米微球的水分散液制备人体植入支架的药物涂层。通过改变反应温度、搅拌方式、反应时间、药物投药量、透析速度和初始水体积来研究在何种条件下制备得到的微球性质最佳。得出结论为其最佳反应温度为30℃、最佳反应时间为60min、最佳透析方法是将纳米微球分散液完全浸入去离子水中,1mL聚己内酯和药物的混合溶液在初始水体积为10mL时滴定,制得的载药纳米微球包封率最高。建立高效液相色谱仪法测量聚己内酯载药纳米微球中雷帕霉素和紫杉醇含量的方法。通过测试得出雷帕霉素和紫杉醇的具体出峰位置以及流动相条件和色谱条件。得出了离心-甲醇萃取雷帕霉素和紫杉醇的方法。甲醇萃取雷帕霉素和紫杉醇的最佳时间分别为2h和1.5h。雷帕霉素和紫杉醇分别在1.0～50ug/mL和1.0～5.0ug/mL具有很好的线性并且方法的重现性好,精密度高。用匀胶机将制得的载药纳米微球均匀涂覆在载玻片表面,干燥除去水分后将其放入PBS缓冲液中,在模仿人体环境的恒温水浴振荡器中研究其缓释情况。通过高效液相色谱仪的方法,来分析未载药的聚己内酯纳米粒子涂层以及不同含量的未载药聚己内酯纳米粒子涂层、不同紫杉醇和雷帕霉素含量对药物缓释的影响以及在酶的作用因素下药物释放量的变化情况。得出结论用去溶剂法制得的载药聚己内酯纳米微球是水分散的,微球表面无迁移。其可作为药物涂层使用并且作为涂层其载药量是可控的。作为药物涂层研究时发现未载药的聚己内酯纳米粒子涂层能有效降低药物释放速度;药物投药量的增加不能有效加快药物释放速度;酶的加入能有效加快药物的缓释速度。尤其是酯酶的加入,对药物释放速度的影响非常明显。更多还原

【Abstract】 Along with the increasingly extensive use of stent,the surface drug coating of the stent began to get the attention of people.Generally,if we just coat the drug on the stent surface,these drug’s half life in the presence of the stent is very short.This will result in a short time of drug action,low utilization rate of drug and toxic side effects.While put the drug and the biodegradable polymers dissolved in a common organic solvent and then coat them on the surface of the stent so that they can form a drug-biodegradable polymer sustained release coating.And it can greatly increased the half life of the drug.It first introduce desolvation method to synthesis of rapamycin-loaded water dispersible-polycaprolatone nanoparticles and synthesis of paclitaxel-loaded water dispersible polycaprolatone nanoparticles.The tradition emulsification desolvation method can not synthetic drug-load nanoparticles that can stay stable in aquecus phase.This article provide the method that synthesis of nanoparticles have solved the problem that using biodegradable polymer or random copolymer prepared drug-loaded nanoparticles that having a stable hydrophilic surface layer.Using this method synthetic rapamycin-loaded polycaprolatone nanoparticles and synthesis of paclitaxel-loaded polycaprolatone nanoparticles can be stable in water.So that we can use it as the drug coating of the body stents.By varying the reaction temperature、mixing method、reaction time、drug dosage、dialysis speed、initial volume of watr to study in which condition the nature of the microspheres are best.The results show that the best reaction temperature is 30℃and the reaction time should be 60 min.Also the best dialysis nanosphere dispersion liquid is that it should fully immersed in deionized water.When ImL water dispersionthe drug-loaded polycaprolatone nanoparticles titrate in the initial water volume of lOmL,the obtained microspheres encapsulating have the highest rate.It introduced a HPLC method for the determination of encapsulation efficiency of rapamycin-loaded and paclitaxel-loaded polycaprolatone nanoporticles.Through test we find the specific peak position of the rapamycin and paclitaxel and their mobile phase’s condition.Finally we get the way of free rapamycin and paclitaxel separated from the drug-loaded nanoparticles,the best extraction time is 2h and 1.5 h and the calibration of the rapamycin curve in the range of 5.0^50 μg/ml and the calibration of the paclitaxel curve in the range of 5.0^50 μ g/mlUse spin coater to coat drug-loaded nanospheres on the surface of the slide uniformly and then put them in a tube containing phosphate buffered saline.The tubes were then placed in a shaking water bath at a thermostatic temperature to study the slow-release of the coating.Use the test to find the best conditions of rapamycin and paclitaxel’s chromatographic conditions.Through the test we can analysis the effect of banknanoparticles coating and different content of blank nanoparticles coating and different cotent of rapamycin and paclitaxel to the drug slow-release.It can conclude that thedrug-loaded polycaprolatone nanoparticles that synthesis by desolvation method is water dispersible and have no migration of its surface.It can be used as drug coating and drug loadings can be controlled.Polycaprolatone without drug nanoparticles can slow the release of the drug.The increase content of drug can’t faster the drug release.The addition of the enzyme can effectively accelerate the speed of the slow release of the drug especially the esterase.更多还原