聚丙交酯乙交酯共聚物作为大分子药物载体

73Vol.7No320095ChineseJournalofPharmaceuticsMay2009p.205:20090112:(1985),(),,,[e-mail];(1962),(),,,Tel.[phone],[e-mail](2009)03020507(,110016)poly(lactide-co-glycolidePLGA)PLGAPLGAPLGAPLGAPLGA;R94ApolylacticacidPLApolyglycolicacidPGApoly(lactide-co-glycolide)PLGAPLGA[1]PLGAPLGA1PLGAL-PLAPGAPLGAD,L-PLAPGAPLGAPLAPLGA[2]PLGAPLGAPLAPGAPLAPGA1:1PLGAPLGAθg37PLGA2067PLGAθgPLA[3]PLGAPLGAPLGA3[4]:123PLGA2PLGA1250µm101000nmPLGA2.1W/O/WPLGAW/OW/O/WW/O/W2.2PLGAW/O[5]2.3PLGA3PLGAPLGA32073.1PLGAPLGAPLGApoly(ethyleneoxide)PEOpolyethyleneglycolPEGKwon[6]PLGAChoi[7]PLGA-PEG-PLGA1(glucagon-likepeptide-1GLP-1)2ABApolyvinylalcoholPVAW/O/WKissel[8]ABAPEOBPLGAAPLGAPLGAABAtetanustoxinTT150000u)ABA[9]TT72%92%ABAPLGAABA5%10%90%5%4453µm3.2PLGALathia[10]PLGAPLGABivas-Benita[11]DNAPLGA-PEI90PLGABreitenbach[12]PVAPLGAPVA-g-PLGA1PVAPLGAPVA-g-PLGAFig.1Structureofpolyvinylalcohol(PVA)-g-poly(lactide-co-glycolide)(PLGA)Jung[13]sulfobutylSBPVASB-PVA-g-PLGAGIgGAIgAPVA2087[14]DNADNA4PLGAFDAPLGAPLGAPLGA4.1PLGAJeong[15]PLGAPEG2PLGA-PEGPLGA-g-PEGFig.2Structureofpoly(lactide-co-glycolide)(PLGA)-g-polyethyleneglycol(PEG)Jiang[16](polymethylmethacrylatePMAA)PLGAPMAAPLGA71%78%PMAA-PLGAPLGAPMAA30uPMAA-PLGA3h4dPMAA-PLGACastellanos[17]solid-in-oil-inwater(S/O/W)PLGAS/O/WγPLGA30%PEG8%γO/WPVAPEGγ32094.2PLGAPLGAKumar[18]W/O/WPLGA1:1F68He[19]DNAPLGA72nm91%DNAPLGA1h80%DNADNADNADNA[20]PLGA[21]PLGAPLGAPLGA-g-PLGA(diethylaminopropylamine-PVA-g-PLGADEAPA-PVA-g-PLGA)[21]DEAPA-PVA-g-PLGAPLGADEAPA5PLGAPLGA,,,,2107[1]BILATIU,ALLEMANE,DOELKERE.Poly(D,L-lactide-co-glycolide)proteinloadednanoparticlespreparedbythedoubleemulsionmethod-processingandformulationissuesforenhancedentrapmentefficiency[J].Microencapsul,2005,22(2):205214.[2]WUXue-shen,WANGNuo.Synthesis,characterization,biodegradation,anddrugdeliveryapplicationofbiodegradablelactic/glycolicacidpolymers.PartII:Biodegradation[J].JBiomedMater,2002,12(1):2134.[3]JAMSHIDIK,HYONSH,IKADAY.Thermalcharacterizationofpolylactides[J].Polymer,1988,29(12):22292234.[4]RAGHUYANSHIRS,SINGHM,TALWARGP.Biodegradabledeliverysystemforsinglestepimmunizationwithtetanustoxoid[J].IntJPharm,1993,93(1):15.[5]RONEYC,KULKARMIP,ARORAV,etal.Targetednanoparticlesfordrugdeliverythroughtheblood-brainbarrierforAlzheimer'sdisease[J].JControlRelease,2005,108(2):193214.[6]KWONYM,KIMSW.Biodegradabletriblockcopolymermicrospheresbasedonthermosensitivesol-geltransition[J].PharmRes,2004,21(2):339343.[7]CHOIS,BAUDYSM,KIMSW.ControlofbloodglucosebynovelGLP-1deliveryusingbiodegradabletriblockcopolymerofPLGA-PEG-PLGAintypediabeticrats[J].PharmRes,2004,21(1):827831.[8]KISSELT,LEEYX,VOLLANDC,etal.ParenteralproteindeliverysystemsusingbiodegradablepolyestersofABAblockstructurecontaininghydrophobicpoly(lactide-co-glycolide)Ablocksandhydrophilicpoly(ethyleneoxide)Bblocks[J].JControlRelease,1996,39(2):315326.[9]KONEBERGR,HIBERTA,KISSELT.Parametersinfluencingthestabilityoftetanoustoxoid[J].EurJPharmBiopharm,1994,40(1):5461.[10]LATHIAJD,LEODONEL,WHEATLEYMA.Polymericcontrastagentwithtargetingpotential[J].Ultrasonics,2004,42(1):763768.[11]BIVASM,ROMEIJNS,JUNGINGERHE,etal.PLGA-PEInanoparticlesforgenedeliverytopulmonaryepithelium[J].EurJPharmBiopharm,2004,58(1):16.[12]BREITENBACHA,KISSELT.Biodegradablecombpolyesters:PartI.Synthesis,characterizationandstructuralanalysisofpoly(lactide)andpoly(lactide-co-glycolide)graftedontowater-solublepoly(vinylalcohol)asbackbone[J].Polymer,1998,39(1):32613271.[13]JUNGT,BREITENBACHA,KISSELT.Sulfobutylatedpoly(vinylalcohol)-graft-poly(lactide-co-glycolide)facilitatethepreparationofsmallnegativelychargedbiodegradablenanospheres[J].JControlRelease,2000,67(1):157169.[14]JUNGT,KAMMW,BREITENBACHA,etal.Loadingoftetanustoxoidtobiodegradablenanoparticlesfrom3211branchedpoly[sulfobutyl-poly(vinylalcohol)-g-(lactide-co-glycolide)]nanoparticlesbyproteinadsorption:Amechanisticstudy[J].PharmRes,2002,19(8):11051113.[15]JEONGB,LEEKM,GUTOWSKAA,etal.Anthermogellingbiodegradablecopolymeraqueoussolutionsforinjectableproteindeliveryandtissueengineering[J].Biomacromolecules,2002,3(4):865868.[16]JIANGHong-liang.Improvementofproteinloadingandmodulationofproteinreleasefrompoly(lactide-co-glycolide)microspheresbycomplexationofproteinswithpolyanions[J].JMicroencapsul,2004,21(6):615624.[17]CASTELLANOSIJ,CRESPOR,GRIEBENOWK.Poly(ethyleneglycol)asstabilizerandemulsifyingagent:Anovelstabilizationapproachpreventingaggregationandinactivationofproteinsuponencapsulationinbioerodiblepolyestermicrospheres[J].JControlRelease,2003,88(1):135145.[18]SATHEESHP,RAMAKRISHNAS,RAMSAINIT,etal.Influenceofmicroencapsulationmethodandpeptideloadingonformulationofpoly(lactide-co-glycolide)insulinnanoparticles[J].Pharmazie,2006,61(7):613617.[19]HEQin,LIUJi,SUNXun,etal.PreparationandcharacteristicsofDNA-nanoparticlestargetingtohepatocarcinomacells[J].WorldJGastroenterol,2004,10(5):660663.[20]CHENGJ,BENJAMINA,TEPLYSY,etal.Magneticallyresponsivepolymericmicroparticlesfororaldeliveryofproteindrugs[J].PharmRes,2006,23(3):18.[21]DAILEYLA,JEKELN,FINKL,etal.Inv