目录中文摘要..................................................1Abstract..................................................2第一章前言...............................................3第二章实验部分...........................................52.1材料与试剂..........................................52.2PEG-P(TMC-DTC)聚合物囊泡的制备....................62.3培美曲塞纳米囊泡药物制备条件筛选....................62.3.1不同Hepes缓冲溶液的筛选.........................62.3.2不同的缓冲液pH值的筛选..........................72.3.3不同的制备温度与转速的筛选.......................72.3.4不同聚合物溶剂和螯合剂的筛选.....................72.3.5不同的钙离子浓度的筛选以及理论载药量的筛选.......72.3.6透析与过柱方法的筛选.............................8第三章结果与讨论.........................................93.1培美曲塞纳米囊泡药物制备条件筛选....................93.1.1不同Hepes缓冲溶液的影响.........................93.1.2不同的缓冲液pH值的影响.........................93.1.3不同的制备温度与转速的影响.....................103.1.4不同聚合物溶剂和螯合剂的影响...................103.1.5不同的钙离子浓度的筛选以及理论载药量的影响......113.1.6透析与过柱的影响...............................11参考文献.................................................15致谢.....................................................16培美曲塞囊泡纳米药物的制备中文摘要培美曲塞（PEM）是一种叶酸拮抗剂，是多靶点抗肿瘤药物，在许多实体瘤包括恶性胸膜间皮瘤中具有良好的临床抗肿瘤活性。然而，PEM在单独使用时体内抗肿瘤活性低，这可能是其细胞穿透能力差、生物利用度低，或是剂量限制性副作用。为了克服这些问题并获得有效的抗肿瘤活性，本论文研究了聚合物囊泡作为纳米药物载体来制备PEM囊泡纳米药物。聚合物囊泡作为纳米药物载体面临着许多挑战，如囊泡粒径不合适、囊泡载药量不理想或制备繁琐等。本论文主要对PEM囊泡纳米药物的主动装载药物进行了探索，优化了不同制备条件。利用动态光散射粒度仪和紫外-可见分光光度计分别测定在不同条件下制备的囊泡纳米药物的粒径大小和载药量，探究不同的条件对囊泡的粒径和载药量的影响，并且优化制备条件使得囊泡纳米药物的粒径和载药量能同时较为理想。关键词：培美曲塞，囊泡，主动装载，抗肿瘤作者：邓礼良指导教师：钟志远教授AbstractPemetrexed(PEM)isamulti-targetedantifolatedrugwithgoodanti-tumoractivityinmanysolidtumorsincludingmalignantpleuralmesothelioma(MPM).However,PEMdoesnotshowsufficientanti-tumoractivityinvivowhenusedalone,possiblyduetoinsufficientcellpenetrationleadingtolowbioavailabilityordose-limitingside-effects.Toovercometheseproblemsandobtaineffectiveanti-tumoractivity,inthisthesiswepreparedPEMpolymersomalnanomedicinesbyapplyingpolymersomesasnanocarrierstoencapsulatePEM.Asdrugnanocarriers,polymersomesfacemanychallenges,suchasimpropersize,unsatisfactorydrugloadingcontentorcomplicatedpreparationprocedure.ThisthesismainlyexploredandoptimizedthepreparationconditionsofPEMpolymersomalnanomedicinesusingactiveloadingmethod.DynamiclightscatteringparticlesizeanalyzerandUV-visiblespectrophotometerwereusedrespectivelyforthedeterminationofpolymersomesizeanddrugloadingcontentofthepreparedpolymersomalnanomedicines.Theeffectsofdifferentpreparationconditionsonthesizeanddrugloadingcontentswereinvestigatedandpreparationconditionsforobtainingidealpolymersomesizeanddrugloadingcontentatthesametimewerescreened.KEYWORDS:pemetrexed,vesicles,activeloading,anti-tumorWrittenby:LiliangDengSupervisedby:Prof.ZhiyuanZhong第一章前言聚合物囊泡自从上个世纪后期开始，很多人投入了...
