脂质体及纳米粒药物递送系统的研究进展

ACTAACADEMIAEMEDICINAESINICAEVol128No14583,#,(,100083):,:;;:R94:A:10002503X(2006)0420583207RecentAdvancesinLiposomesandNanoparticlesasDrugCarriersforDrugDeliveryLIUYang,LBWan2liang#,ZHANGQiang(DepartmentofPharmaceutics,SchoolofPharmaceuticalSciences,PekingUniversity,Beijing100083,China)ABSTRACT:Liposomesandnanoparticleshavebeenusedasdrugcarrierstoincreasesolubility,prolongdrugdurationinvivo,targetdrugdelivery,reducetoxicityandcombatmulti2drugresistance1Withmajorad2vancesinthepreparationtechniques,preparationmaterial,andsurfacemodifiersinrecentyears,liposomesandnanoparticlesdeliverysystemshaveachievedsuccessinfieldsincludingcancertherapy,overcomingbiolo2gicalbarriers,andbiologicaldrugsandvaccinecarriage1Keywords:liposomes;nanoparticles;drugdeliverysystemActaAcadMedSin,2006,28(4):583-589,,:(liposomes);,()pH;,10FDA(Doxil,Caelyx,)[1,2]Doxil,(nanoparticle)11000nm,(nanospheres);(nanocapsules)20051FDA(Abraxane),20[3]#CorrespondingauthorTel:010282802683,Fax:[phone],E2mail:luwl@bjmu1edu1cn584August,2006,,(),pH,,,pH,(Doxil)pH,:(1);(2);(3):(1),(2)(hydra2tion);,,,,,,,(1000),,:DOXNH3ClZDOXNH3++Cl-1ZDOXNH2+HCl,DOXNH3ClDOXNH3+Cl-1DOXNH2HClDOXNH2,[4],,,(NH3),,NH3(drivingforce);,,,;SO42-,(),,pH,Chiu[5]2,(iono2phore)A23187(calcimycin,CAL,)pH[5,6]A23187H+M+(Li+Na+K+Cs+)M2+(Ca2+Mg2+Mn2+),,A23187pH[7],,SPI277(SPI2077,),[8,9]1999Bandak[10],SPI2077,3,,,10%,SPI277,,(polylacticacid,PLA)(polyglycolicacid,PGA)2(polylactic2glycolicacidco2polymer,PLGA),PLAPL2Vol128No14585GAFDA,,,,,[11],(OH-CH3O-CH3COO-),,,(pH=110315),70/40/10188/184/237;20/40/80[11],PLAFDA,,,,PLA,,10000,,,[11],(polyethyleneglycol,PEG)(reticuloendothelialsystem,RES),RES(),PEGPEG,RES,,PEG,,(conformationalclouds)[12,13],,,RES[14]PEGpH,()Ishida[15]pH80%12h,pH61541590%PEG,,1987Felgner[16],,18%,,RNA,siRNA,siRNA[17]Zhang[18](R8)2RNA(humandoubleminutegene22siRNA,HDM22siRNA),,3MatsumuraMaeda[19](enhancedperme2586August,2006ationandretention,EPR),,EPR[20,21],,,,[22],,,(monoclonalantibodies,mAbs),mAbs[23,24],mAbs,mAbs,,mAbs,,mAbs,:CD219,,B[25](Fab)mAbs,,,[26],Fc,,,Xiong[27]22(arginine2glycine2asparticacidmimeticmodifiedstericallystabilizedliposomes,RGDm2SSL),,RGDm2SSL:[28];pH[29,30];,[31][32]10,,(multidrugre2sistance,MDR),Li[33,34]:,,,MDRHL260,MDRHL260;,P2(efflux),,Ca2+,,,,CTT(CTTHWGFTLC)992Tc,,[35]v32(magneticreso2nanceimaging,MRI),,[36,37],,,(bloodbrainbarri2er,BBB)BBB(centralnervoussystem,CNS),BBBDalargin80Dalargin,[38]80,80Vol128No14587[39],:[40][41][42][43]BBB,,(convection2enhanceddelivery,CED)[44],BBB:,,,,,,,,,Elaine[45],,70100min,34Ma[46]100U/kg11hGoto[47](fusogenicliposomes)(sendaivirus),,,,Singh[48]gp41[21(humanimmunodeficiencyvirus21,HIV21)],12130000Mishra[49](HBsAg),Balb/c,HBsAgHBsAgIgG(P01005),,,;,,,Doxil1200/,,,,,,RES1MarkmanM,GordonAN,McGuireWP,etal1Liposomalan2thracyclinetreatmentforovariancancer1SeminOncol,2004,31(6Suppl13):91210512KrownSE,NorthfeltDW,OsobaD,etal1Useofliposomalan2thracyclinesinKaposi’ssarcoma1SeminOncol,2004,31(6Suppl13):3625213FelnerovaD,ViretJF,GluckR1Liposomesandvirosomesasdeliverysystemsforantigens,nucleicacidsanddrugs1CurrOpinBiotech,2004,15:518252914BarenholzY1Liposomeapplication:problemsandprospects1CurrOpinColloInterfSci,2001,6(1):6627715ChiuGN,AbrahamSA,IckensteinLM,etal1Encapsulationofdoxorubicinintothermosensitiveliposomesviacomplexationwiththetransitionmetalmanganese1JControlRelease,2005,104(2):271228816AbrahamSA,EdwardsK,KarlssonG,etal1Anevaluationoftransmembraneiongradient2mediatedencapsulationoftopotecanwithinIiposomes1JControlRelease,2004,96(3):449246117PrabhanandaBS,KombrabailMH1Evidencefordimerpartici2pationandevidenceagainstchannelmechanisminA231872me2diatedmonovalentmetaliontransportacrossphospholipidvesic2ularmembrane1BiophysJ,1998,75:17492175818KimES,LuC,KhuriFR,etal1Aphasestudyofstealthcisplatin(SPI277)inpatientswithadvancednon2smallcelllungcancer1LungCancer,2001,34(3):427243219HarringtonKJ,LewanskiCR,NorthcoteAD,etal1Phase2studyofpegylatedliposomalcisplatin(SPI2077)inpatientswithinoperableheadandneckcancer1AnnOncol,2001,12(4):4932496110BandakS,GorenD,HorowitzA,etal1Pharmacologicalstudi2588August,2006esofcisplatinencapsulatedinlong2circulatingliposomesinmousetumormodels1AntiCancerDrugs,1999,10(10):9112920111SoppimathKS,AminabhaviTM,KulkarniAR,etal1Biode2gradablepolymericnanoparticlesasdrugdeliverydevices1JControlRelease,2001,70(122):1220112TorchilinVP1Polymer2coatedlong2circulatingmicroparticulatepharmaceuticals1JMicroencapsul,1998,15(1):1219113BelsitoS,BartucciR,MontesanoG,etal1Molecularandme2soscopicpropertiesofhydrophilicpolymer2graftedphospholipidsmixedwithphosphatidylcholineinaqueousdispersion:interac2tionofdipalmitoylN2poly(ethyleneglycol)phosphatidyletha2nolaminewithdipalmitoylphosphatidylcholinestudiedbyspec2trophotometryandspin2labelelectronspinresonance1BiophysJ,2000,78(3):142021430114PeracchiaMT,HarnischS,Pinto2AlphandaryH,etal1Visua2lizationofinvitroprotein2rejectingpropertiesofPEGylatedstealth(R)polycyanoacrylatenanoparticles1Biomaterials,1999,20(14):126921275115IshidaT,OkadaY,KobayashiT,etal1Developmento