pH-敏感型纳米制剂概述

72Vol.7No.220093ChineseJournalofPharmaceuticsMar.2009p.72:200807041985,,,,Tel.[phone],[e-mail];1962,(),,,Tel.[phone],[e-mail](2009)02007205pHpHpHpHpHpHpHR94ApH37pH6.5pH7.4[1]pHpHpHpHpHpH[2]60hpH7.46.5pHpHATPpH6.5pH7.5pHpHpHipHpHepHpH[1]pHpKapHpHmRNApHpH4.58.0pHpKa5.0~8.0pHpH273pHpH1HydrophobicdrugPEG/PEOchainsHydrophilictailAttacheddrugHydrophilicdrugHydrophobictailEncapsulateddrugPhospholipidgroupsLiposomePolymericnanoparticleMicelleDendrimerFig.1DifferenttypesofpH-sensitivenanocarrierspHpH-sensitivepolymericnanoparticlepHpHpHβpoly(β-aminoester)PbAEpH6.5PbAEPbAEpolycaprolactam,PCLpH[3]Fan[4]N[poly(N-isopropylacrylamide),NIPAAm]/pHNIPAAm4:1pHTBpHpH(pH-sensitiveliposome)1920pHpHpHpH7.4~6.5pHpHpH[5]Cho[6]pHpH6pH5pH5pHphosphatidylethanolamine,PE747[7]pH[8]polyethyleneglycolPEGreticuloendothelialsystemRESPEGpHPEGpHNIPAAm[9]oleicacid,OA)cholesterolhemisuccinate,CHEMSN-palmitoylhemocysteine,PHCN-succinyl-dioleoy-phosphatidyl-ethanolamine,SOPE[10]pHpHLee[11]pKapH35(6)pHpHpH,pHpH-sensitivemicelle)20~100nm[12]RES[13]pH[14]pH5.07.4[15]pHpH5.06.0pH4.05.0BaepHpH[16]pHLL[17][18]LL/PEGL/PEGpHpH-sensitivedendrimer275Tomalia[19]2,2[20]pHPEO-dendrimer[21]PEO-dendrimer,pHpHpH[1]VAUPELP,KALLIOWSKIF,OKUNIEFFP.Bloodflow,oxygenandnutrientsupply,andmetabolicmicroenvironmentofhumantumors:areview[J].CancerRes,1989,49(23):64496465.[2]HUNTCA,MACGREGORRD,SIEGALRA.EngineeringtargetedinvivodrugdeliveryI.Thephysiological&physicochemicalprinciplesgoverningopportunities&limitations[J].PharmRes,1986,3(12):333344.[3]DEVALAPALLYH,SHENOYD,LITTLES,etal.Poly(ethyleneoxide)-modifiedpoly(beta-aminoester)nanoparticlesasapH-sensitivesystemfortumor-targeteddeliveryofhydrophobicdrugs:part3.Therapeuticefficacyandsafetystudiesinovariancancerxenograftmodel[J].CancerChemotherPharmacol,2007,59(4):477484.[4]FANli,WUhong,ZHANGhui,etal.NovelsuperpH-sensitivenanoparticlesresponsivetotumorextracellularpH[J].CarbohydrPolym,2008,73(3):390400.[5]PAPANICOLAOUI,BRIGGSS,ALPARHO.IncreasedresistanceofDNAlipoplexestoproteinbindinginvitrobysurface-modificationwithamultivalenthydrophilicpolymer[J].DrugTarget,2004,12(8):541547.[6]CHOEC,LIMHJ,KIMHJ,etal.RoleofpH-sensitivepolymerliposomecomplexinenhancingcellularuptakeofbiologicallyactivedrugs[J].MaterSciEng,2008,28(7):10311036.[7]FATTALE,COUVREURP,DUBERNETC.“Smart”deliveryofantisenseoligonucleotidesbyanionicpH-sensitiveliposomes[J].AdvDrugDelivRev,2004,56(7):931946.[8]KAKUDOT,CHAKIS,FUTAKII,atel.Transferrin-modifiedliposomesequippedwithapH-sensitivefusogenicpeptide:anartificialviral-likedeliverysystem[J].Biochemistry,2004,43(19):56185628.[9]ROUXE,PASSIRANIC,SCHEFFOLDS,etal.Serum-stableandlong-circulating,PEGylated,pH-sensitiveliposomes[J].ControlRelease,2004,94(2):447451.[10]COUFFINAC,LEROUXJC.Reportontheuseofpoly(organophosphazenes)forthedesignofstimuli-responsive767vesicles[J].Biomacromolecules,2004,5(6):20822087.[11]LEERJ,WANGS,TURKP,etal.TheeffectsofpHandintraliposomalbufferstrengthontherateofliposomecontentreleaseandintracellulardrugdelivery[J].BiosciRep,1998,18(2):6978.[12]KATAOKAK,HARADAA,NAGASAKIY.Blockcopolymermicellesfordrugdelivery:design,characterizationandbiologicalsignificance[J].AdvDrugDelivRev,2001,47(1):113131.[13]KWONGS,OKANOT.Polymericmicellesasnewdrugcarriers[J].AdvDrugDelivRev,1996,21(2):107116.[14]GILLIESER,FRECHETJMJ.Developmentofacidsensitivecopolymermicellesfordrugdelivery[J].PureApplChem,2004,76(7):12951308.[15]BAEY,NISHIYAMAN,FUKUSHIMAS,etal.PreparationandbiologicalcharacterizationofpolymericmicelledrugcarrierswithintracellularpH-triggereddrugreleaseproperty:tumorpermeability,controlledsubcellulardrugdistribution,andenhancedinvivoantitumorefficacy[J].BioconjugChem,2005,16(2):122130.[16]NAK,LEEES,BEAYH.Adriamycinloadedpullulanacetate/sulfonamideconjugatenanoparticlesrespondingtotumorpH:pHdependentcellinteraction,internalizationandcytotoxicityinvitro[J].ControlRelease,2003,87(13):313.[17]LEEES,SHINHJ,NAK,etal.Poly(L-histidine)-PEGblockcopolymermicellesandpH-induceddestabilization[J].ControlRelease,2003,90(3):363374.[18]LOWPS,LEERJ.Folate-mediatedtumorcelltargetingofliposomeentrappeddoxorubicininvitro[J].BiochemBiophysActa,1995,1233(2):134144.[19]TOMALIADA,BAKERH,DEWALDJR,etal.Anewclassofpolymers:starburst-dendriticmacromolecules[J].PolymJ,1985,17(1):117132.[20]IHREHR,PADILLAOL,JESUD,etal.Polyesterdendriticsystemsfordrugdeliveryapplications:design,synthesis,andcharacterization[J].BioconjuChem,2002,13(3):443452.[21]GILIESER,JONSSONTB,FRECHETJMJ.Stimuli-responsivesupramolecularassembliesoflinear-dendriticcopolymers[J].AmChemSoc,2004,126(38):1193611943.AreviewonpH-sensitivenanocarriersfordrugdeliveryWANGYu,WANGDong-kai,SUNNian(SchoolofPharmacy,ShenyangPharmaceuticalUniversity,Shenyang110016,China)AbstractObjectiveTointroducepH-responsivenanocarriersfordrugdeliveryandtheircurrentdevelopment.MethodsPertinentliteratureswereanalyzed,comparedandsummarized.ResultsNanotechnologyhasshowntremendouspromiseintarget-specificdeliveryofdrugsinvivo.BasedonthepHdifferencebetwe