多孔有机-无机纳米复合材料的制备及其药物缓释性能研究

上海交通大学硕士学位论文多孔有机-无机纳米复合材料的制备及其药物缓释性能研究姓名：周正阳申请学位级别：硕士专业：材料学指导教师：张荻;朱申敏20070101--1.SBA-15SBA-PNIPA-Fe2O3PNIPAFe2O32.FeCl2-SBA-15PNIPAIBU3.Fe(CO)5-Fe(CO)5-P1238.2nmSBA-15PNIPA4.SBA-156.5nm0.72cm3g-15.ATRPMCFPNIPA58wt%(IBU/Silica)SBA-15PNIPAATRPABSTRACTSynthesisandInvestigationofFunctionalInorganic-OrganicNanocompositeandItsApplicationasDrugDeliverySystemABSTRACTMesoporousmaterialshavemanypotentialapplicationsduetotheirlargespecificsurfacearea,largeporevolume,uniformporesize,controllablemorphology,easilyfunctionalizedsurfaceandhighlyorderedporestructure.Theresearchonmesoporousmaterialsiscurrentlychangingtotheexploitationoftheirapplications.Oneofthehottopicsistheapplicationofmesoporousmaterialsinthecontrolled-releasesystemsandbio/lifesciences.Inthisthesis,wefocusedonthesynthesisofmultifunctionalnanocompositesbasedonhighlyorderedmesoporoussilicaandtheirapplicationsincontrolleddrugdelivery,whichhavegreattheoreticalandpracticalsignifications.Theresearchrelatestoseveralhotfields,includinglifescience,nano-scienceandtechnologyandmesoporousmaterialsscience.Themaincontentsofourworkaresummarizedasfollows:1.SynthesizinganovelmultifunctionalnanocompositesbasedonmeosoporoussilicaSBA-15withthermoresponsivePNIPAandmagneticnanoparticlesFe2O3intheporechannelsthroughnanocastingmethodandultrasonication.Thehighsurfacearea,highlyorderedporestructureandmultifunctionalpropertiesprovideafire-newmethodtofabricateanewcontrolled-releasesystem.2.EmployinghydrophilicFeCl2asanadditionalprecursortofabricatepowderSBA-15withmagneticparticlesformedinsituviasurfactanttemplatesol-gelprocessandfurtherdevelopedthemethodtosynthesizenano-coatingPNIPAinsidetheSBA-15channels.TheinvitrotestofIBUloadingandreleaseillustratedthesystemhadagreatpotentialuseforthermo-responsivecontrolleddrug-release.ABSTRACT3.ChoosinghydrophobicFe(CO)5asthemagneticprecursorsourceviasurfactanttemplatesol-gel,andcontroloftransportthroughpolymerizationofPNIPAtoformthestimuli-responsivesystem.Interestingly,inadditiontoactasthesourcesoftheresultantmagneticparticles,Fe(CO)5canplayasaswellingagent,whichcanguaranteealargeporesize8.2nm.BasedontheinvitrotestofIBUloadingandrelease,wefoundthisnovelsystemcanactasconventionalreservoirfortargetandthermo-responsivecontrolleddrugrelease.4.FabricatinganoveldeliverycarriersystembasedontheorderedmesoporoussilicaSBA-15withhydrophobicpolyisoprenepolymerizedintheporesnetwork.Itisinterestingtofindtheresultsystemstillholdsarelativelylargeporesize(6.5nm)andporevolume(0.72cm3g-1),whichwillbenefitforthestorageofdrugswithrelativelylargemolecules.5.Adrugdeliverysystembasedonthermo-responsivePNIPAinsidemicrostructurecellularfoammaterialsMCFviaATRPwassynthesizedsuccessfully(MCF)withalargeporediameter.ItisinterestingtofindthedrugsystemofMCF-PNIPAdemonstratedahighibuprofen(IBU)storagecapacityof58wt%(IBU/silica).KEYWORDS:SBA-15,Controlleddrugrelease,Stimuli-responsive,Multi-functional,PNIPA,ATRP20072620072620072611.1(2-50nm)(IUPAC)(porousmaterial)[1]2nm(micropore)250nm(mesopore)50(macropore)0.7nm1mm1970[2]1992MobileMCM-41[3]SiO2SBA-151.2[4,5][6][7][8,9][10,11]-()(2)1)CmH2m+1(CH3)3N+BrCmH2m+1(CH3)3N+Cl2)CmH2m+1COONaCmH2m+1OPO3H2CmH2m+1OSO3HCmH2m+1OSO3Na3)CmH2m+1NH2-(PEO-PPO)4)()(I)S+I-(S+I)--S+XI+S+XClSO42,NO3I+S+XI+I+XS+SM+I(MNa+,K+)S0I0S0S0I0S0I0S0I0S-I(V)S-I/1992MobilM41SMCM-41MCM-48MCM-503a.FSM-161990Yanagiawa[12]NaHSi2O5·3H2O(ATMA)Inagaki[8,13]FSMb.HMSTanev[14,15]S0-I0HMSc.SBA-nStucky[16-18]CnH2n+1N+Me2(CH2)SN+Me2CmH2m+1(Cn-s-m)SBA-1(Pm3n)SBA-2(P63/mmc)SBA-3(P6m)--(PEO-PPO-PEO)4.6-30nmSBA-15[19,20]PEOSBA-16[20]17.6nmd.KIT-1Ryoo[21]MCM-41e.MSU-xS0-I0[22,23]1.24(LiquidCrystalTemplatingMechanismLCT)Beck[3,24]MCM-411-1MCM-41X-MCM-41()()LCTLCT1-1Fig.1-1LiquidCrystalTemplatingMechanism(TheCooperativeFormationMechanismCFM)MCM-41(mesophase)()5[17](5%)[25,26][18]Davise[27,28]Stucky[29]Davis23SiO2MCM-41(1-2)1-2Fig.1-2SilicateRodAssembleModel1-3Fig.1-3CooperativeFormationMechanismStucky[30]-6-(1-3)Stucky[16](eneralizedliquidcrystaltemplatingmechanism)(1)(cooperativechargematchedtemplating)(2)(ligand-assistedtemplating)(3)(neutraltemplating)Monnier[31]()Inagaki[32]AttardAntonietti[33,34]1.3Lin[35]2-2.3nm200nmMCM-41(MSN)1-4MSNCdSMSN[36]MSNCdSMSNLin[37]MSN1-5MSNMSN3--[38]Fe3O4MSN71-4MSNCdSFig.1-4Controlled-releasemechanismofCdSnanoparticle-cappedMSNsystems1-5MSNFe3O4Fig.1-5Controlled-releasemechanismofFe3O4nanoparticle-cappedMSNsystemsXiao[39]SBA-15PDDAPH1-6PDDASBA-15SBA-15SBA-1536wt%PHPH81-6SBA-15PHFig.1-6SchematicrepresentationofpH-responsivestorage-releasedrugdeliverysystem1.4199210SBA-15PNIPAFe2O3FeCl2-SBA-15PNIPAIBUFe(CO)5-Fe(CO)5-P1239PNIPASBA-15MCFPNIPA58wt%(IBU/Silica)10[1]IUPACManualofSymbolsandTerminology,PureAppl.Chem.1972,31:578.[2]F.DiRenzo,H.Cambon,R.Dutartre,MicroporousMater,1997,10:283-286.[3]C.T.Kresge,M.E.Leonowicz,W.J.Roth,J.C.Vartuli,J.S.Beck,Nature1992,359:710.[4]K.J.Edler,J.W.White,Chem.Commun.1995,155.[5]M.Chatterjee,T.Iwasaki,H.Hayashi,Y.Onodera,T.Ebina,T.Nagase,Catal.Lett.1998,52:21.[6]W.Lin,J.Chen,Y.SunW.Q.Pang,Chem.Commun.1995,2367.[7]Wu,C.G.