环醚侧基修饰的pclpeg嵌段共聚物可注射温敏凝胶及肿瘤局部给药的研究-study on injection of pcl peg block copolymer modified by cyclic ether pendant groups into thermosensitive gel and local administration of tumor.docx

下载文档 降价啦

5
0
约13.79万字
约 137页
2018-05-26 发布于上海
举报
版权申诉
保障服务

环醚侧基修饰的pclpeg嵌段共聚物可注射温敏凝胶及肿瘤局部给药的研究-study on injection of pcl peg block copolymer modified by cyclic ether pendant groups into thermosensitive gel and local administration of tumor.docx

1、本文档共137页，可阅读全部内容。
2、有哪些信誉好的足球投注网站（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。

环醚侧基修饰的pclpeg嵌段共聚物可注射温敏凝胶及肿瘤局部给药的研究-study on injection of pcl peg block copolymer modified by cyclic ether pendant groups into thermosensitive gel and local administration of tumor

ABSTRACTLoco-regionalchemotherapyofthermosensitiveinsituhydrogelcomposedofPEGandbiodegradablepolyesterscanprovidephysiologicaltargetforanticancerdrugs,improvetheantitumorefficiencyaswellasreducethesystemicexposureandtissuedistribution.PCL-PEG-PCLcopolymersarebiocompatible,however,toprepareofPCL-PEG-PCLhydrogel,onemustdissolvePCL-PEG-PCLinwateratahightemperatureandthenquenchthesolutionat0oC.AndtheinstabilityofPCL-PEG-PCLsol,thetooslowdegradationanddrugreleasepropertiesofPCL-PEG-PCLrestrictthebiomedicalapplicationsofPCL-PEG-PCLgel.Inthisstudy,pendentcycleetherswereintroducedintoPCLtoobtainPECTtoovercomethesesdisadvantages.Thegeltransiton,degradationandpaclitaxelrelease,antitumoreffectofpaclitaxelloadedPECThydrogel(PTX/PECTGel)andpaclitaxelpharmacokineticswereinvestigated.ThebiocompatibilityofPECTwasalsostudied.PECTwassynthesizedbyring-openingcopolymerizationofε-caprolactoneand1,4,8-trioxa[4.6]spiro-9-undecanonewithPEGastheinitiatorandcatalyst.ThermodynamicanalysisdemonstratedthatcycleetherscouldweakenthecrystallinityofPCLaswellasimparthydrophilitytoPCL.Thus,PECToritsfree-driedpowderscouldbequicklydissolvledinwateratroomtemperature,formingstablecore-shellstructurePECTnanoparticlesaqueoussolution.Atbodytemperature,PECTnanoparticlesaggregatedintogeldrivenbyhydrophobicinteractionandthecrystallinityofhydrophobicmicrodomains.Theconvenientfabricationofdrugformulation,satisfactorydegradabilityandwell-controlleddrugreleaseprofilearecrucialfactorsforinjectablehydrogelformulationsinclinicalapplications.Bydissolvingfreeze-driedpowdersofpaclitaxel(PTX)-loadedPECTnanoparticlesinwateratambienttemperaturecouldprovidemuchconvenienceforclinicalPTXencapsulatedPECThydrogelformulation(PTX/PECTGel).Furthermore,thepaclitaxeldistributioninPTX/PECTGelwasmoreamorphousandhomogeneous.AsmallamountofpendantcyclicethergroupsinPCLcouldtunetheinvitroandinvivoretentiontimeofPECTgelandtheincorporatedpaclitaxelreleasefromafewweekstomonths.Significantly,paclitaxel-loadedPECTnanoparticlescoulddissociatefr