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*71006925。。*E-mailhaohong@nwu.edu.cnSLZ2009011、131152007ZDKG－502010-03-292010-09-14、。、、、。。ResearchProgressofPolymericProdrugsWangJunlianHaoHong*WangYangShiMeiSchoolofChemicalEngineeringNorthwestUniversityXi'an710069AbstractPolymericprodrugshavebeendrawingattentionbecausetheycancontroldrugreleasereducesystemictoxicityoflowmolecularweightdrugsimprovetargetingandselectiveofantineoplasticdrugsandenhancestabilityandbioavailabilityofpeptidesproteinsandoligonucleotides.Therecentadvanceofpolymericprodrugsincludingtheeffectofpolymericcarriermaterialonthedrugloadingbiocompatibilityandrenalexcretionwerereviewed.Inadditionthemethodsabouttheterminalgroupmodificationofcarriersanddrugsreductionofsterichindrancespecifictargetingligandsinchemicalsynthesiswerediscussedtoo.Finallytheresearchprospectsandissuesfacedinthisfieldwerepointedout.KeywordsPolymerCarrierProdrugControlledrelease1975Ringsdorfpolymericprodrugs、、3。、、。、、。、1。。。、、。1Ringsdorf。·131·http//。Iyer3400nm4。。Krakovicǎová5DoxorubicinDOXN-2-HPMAHPMAHPMA10。、、、、、、。Huang6lactoferrinLf-PAMAMPEGPAMAM-PEG-Lf。PAMAM-PEG-LfPAMAM4。12Fig.1Mainstagesofreceptor-mediatedendocytosis22。、。2.1Hoste11、、、234。。2.1.1HPMAPEG。PEG、、7。-PEG-adenosinedeaminase、-PEG-asparaginase、-α2bLinearPEG-interferonα2b、-VEGFBranchedPEG-anti-VEGFaptamerPEG8～11。PEG、、12。PEG13。PEGPEG2PEG·231·2011742http//。1973HPMAHPMA。Duncan14HPMA-DOXHPMA-DOX1/4DOX。DOXSeymour15HPMA-DOX。、。。PaclitaxelTXL2′-αβ-N-2--DL-PHEAPHEA-TXL16TXL。PGANN-NN-DimethylsphingosineDMSPPGA-DMSP17DMSPDMSP18%。、、PGA。2.1.2CTSCTS18～20。21Tca8113、KBDOKTca8113、KBDOK1mg/mLTca8113KB。Li22stavudineD4TCTS-。6h6.84%D4T2～31/3～1/4。、、23。Dextran。Varshosaz24budesonideBSDBSD-10、BSD-70BSD-500。10%BSDBSD-70。、。ibuprofenBLF5400nmBLF。。2.2PEGCTS、PGA、PLA。、、25。Sehiavon26PEGPEG11。Marina27PEG。PEG6。CTS、、。CTSLu28CTS。N-。0.5N-。29L-PLLA·331·http//～32。PET-PLGAPETPET-PLGA。2PET-PLGA29Scheme2SyntheticrouteofStar-shapedPET-PLGA29。。、、30。11G0、G1、G2。Abhinav31EDAMichaelG5PPIPADPAD-PPIDOXPAD-PPIPAD-PPI-DOXDOX。Donald32。2.3、。2.3.1、pH。。Kato33SA。。SAbudesonideBSD2215hSA30%。。Cruz34N-NHSN-·431·2011742http//。NHS3。334Scheme3NHSestersreactwithnucleophilestoreleasetheNHSleavinggroupandformanacetylatedproduct342.3.2。PEG35。。、、。Shechter36insulin9-FmocPEGPEG40-Fmoc-insulinFmocPEGPEG40-Fmoc-insulint1/230h4～7。Tsubery37PYY3-36MAL-FMS-OSUPEGPEGPYY3-36t1/23h24hPYY3-36PYY3-367～8。2.3.3、EPR。、、、、、。methotrexateMTXCTS3833.8%CTS8%。MTX-LCH。MTX-CHCTS—NH2—NH+3。Pasut39FolatemPEG-gemcitabinedFdCmPEG5000-dFdC、Folate-mPEG4800-dFdC。HT-29、KB-3-12～3t1/2dFdC5～10。3、、。。me-too。、、。。、。“21”·531·http//。1KHosteKDWinneESchacht.Int.J.Pharm.20042776119～131.2JKhandareTMinko.Prog.Polym.Sci.20063110359～397.3AKIyerGKhaledJFangetal.Drug.Discov.Today200691117～18.4VTorchilin.Adv.DrugDeliv.Rev.2010DOI10.1016/j.addr.2010.03.011.5HKrakovicǎováTEtrychKUlbrich.Eur.J.Pharm.Sci.2009374405～412.6RQHuangWKeYLiuetal.Biomaterials2008298238～246.7GPasutFMVeronese.Prog.Polym.Sci.2007326933～961.8YLevyMSHershfieldMCFernandezetal.J.Pediatr.19881135312～317.9LMGraham.Adv.DrugDeliv.Rev.20031021293～302.10YSWangSYoungsterMGraceetal.Adv.DrugDeliv.Rev.2002546547～557.11DTShimaPCaliasJETCunninghametal.Nat.Rev.DrugDiscov.200659123～132.12RBGreenwald.J.Control.Release20017412159～171.13SSchreiberPRutgeertsRNFedoraketal.Gastroenterology200512910807～818.14RDuncanBBriefing.Pharm.Tech.20018178～184.15LWSeymourDRFerryDAndersonetal.J.Clin.Oncol.20022091668～1676.16GMlicciardi.Eur.J.Phar.Bio.2004584151～59.17CPZouMBrewerXYCao.Gynecologic.Oncol.20071079441～449.18HZQuanFZhuXYHan.Med.Hypoth.2009736205～06.19MGodardKDécordéEVentura.FoodChem.20091159176～180.20AMNeyrinckLBBindelsFDBackeretal.Int.Immuno.Pharm.200995767～73.21.20092511153～155.22LYangRZengCLi.Bio.Med.Chem.201018117～123.23.200812352～65.24JVarshosazJEmamiNTavakolietal.Int.J.Pharm.2009365269～76.25.200997511～513.26OSchiavonGPssutSMoro.Eur.J.Med.Chem.2004398123～13327ZMarinaDLGabriella.Eur.J.Pharm.2007306343～350.28SJLuXFSong.J.Appl.Poly.Sci.20049143497～3503.29.2008.30MFBranaGDominguezBSaez.Eur.J.Med.Chem.2002374541～551.31AAgarwalUGuptaAAsthanaetal.Biomaterials20093073588～3596.32ADonaldJMTomaliaa.Prog.Polym.Sci.2005309217～219.33YKatoHOnishiYMachida.Biomaterials2004256907～915.34LJCruzEIglesiasJCAguilaretal.J.Pept.Sci200175511～518.35DHKenneth.SWKim.Adv.DrugDeliv.Rev.2002546505～53036YShechterMMironchikSRubinraut.Eur.J.Pharm.Bio.200870419～28.37HTsuberyYShechteraMMironchiketal.FEBSLett.200557992439～2444.38.20072861092～1097.39GPasutFCanalLDViaetal.J.Control.Release20081278239～248.·631·2011742http//