肺部给药传递系统的研究进展

ChineseJournalofNewDrugs2009,18(8)6942009188[](863)(2007AA02Z171)[],,,:13512538411,E2mail:[e-mail][],,,:[phone],E2mail:[e-mail],,(,210009)[],,,,[];;;;;[]R944.9[]A[]1003-3734(2009)08-0694-05AdvancesinpulmonarydeliverysystemsWANGMian,ZHUJia2bi,TANGYue(InstituteofPharmaceutics,ChinaPharmaceuticalUniversity,Nanjing210009,China)[Abstract]Thelunghasthepropertiesofthinalveolarepithelium,hugesurfacearea,richbloodcapillaryandrelativelyfewmetabolicreactions,allofwhicharebenefittoabsorbandtransportthedrugs.Sothelungbe2comestheimportanttargetorganofsomedrugs,includingsomeproteindrugswhichcanbedegradedeasilybyen2zymeandsomedrugswhichcurelungdiseases.Withtherapiddevelopmentofmaterialscience,theresearchonthenewpulmonarydosageformshasbeenonehotpointofpharmaceuticalresearch.Incorporationwiththephysio2logicalbasisofthelungandthedrugstothelung,thisarticletakestheviewpointsofthecharacteristicsofdosageforms,modeldrugs,carriermaterialsandpreparationstoprovidethelatestadvancesonsomenewpulmonarydos2ageforms,includingnanoparticles,porousnanoparticle2aggregateparticles,microspheres,largeporousparticlesandliposome.[Keywords]pulmonarydelivery;nanoparticles;porousnanoparticle2aggregateparticles;microspheres;largeporousparticles;liposome,:,;,,2050,20,,,,,2,,,ChineseJournalofNewDrugs2009,18(8)69520091881,,[1],5060m,0.2m[2];2.5m2,43102m2[2-3],,,0.51m[1],2,[1],,,E,,,,,3,,,,,,,,,44.1(nanoparticles),,,Yamamoto[4],2/(PLGA)2PLGA1%(20mL)1%(150000,1mL)5min,2PLGA,,,24h,,,,Sharma[5],2PLGA,350400nm,54%66%PLGA,,67d,1314dPLGA,46d,89d,PLGA,PLGAVaughn[6]80407,,,10Zahoor[7],3,15d45d,,,,,,,,,,,4.2(porousnanoparticle2aggregateparticles,PNAPs)PNAPs[8],()PNAPs,ChineseJournalofNewDrugs2009,18(8)69620091881015m,13m,[9]/Grenha[10],,PNAPsPNAPs,23m,0145gcm-3,;,PNAPs,ZetaGrenha[11](Dipalmitoylphosphatidylcho2line,DPPC),/,PNAPsPNAPs23m,0.40.5gcm-3Hadinoto[12],,,PNAPs,PNAPsPNAPs1015m,3mCook[13]60,,DPPC,,PNAPs(3.930.12)m,(46.51.8)%4.3(microspheres),(polylacticacid,PLA)(polyglycolicacid,PGA)PLGA,Emami[14]/2PLGA,(responsesurfacemethodology),15mBlanco[15]52,(1.10.5)(1.70.9)mPLAPLGA,PLAPLGA(75/25)PLGA(50/50)Hitzman[16]52,PLA,PLGA,/,,,PLAPLGA,/Skiba[17]2,,2,5m,4.4(largeporousparticles,LPPs),(0.4gmL-1),(1020m)[18],,[19]12m,,,[20-21],,Rawat[22],PLGA,//2603,,,56Unqaro[18]//2PLGA,22(Hydroxypropyl22cyclodex2trin,HPCD),,,,HPCD,HPCD,,Kwon[23],,//2PLGA22.5m,2.9mPLGAGiovaqnoli[24],//2PLGA,,4.5(liposome)ChineseJournalofNewDrugs2009,18(8)6972009188,,,,,,,,Huang[25],40%1m,,[26],,1,,,,,23Bi[27]2,,,,38.38%,,5,,[][1]PATTONJS.Mechanismsofmacromoleculeabsorptionbythelungs[J].AdvDrugDelivRev,1996,19(1):3-36.[2]WEIBELER.Morphologicalbasisofalveolar2capillarygasex2change[J].PhysiolRev,1973,53(2):419-495.[3]STONEKC,MERCERRR,GEHRP,etal.Allometricrelation2shipsofcellnumbersandsizeinthemammalianlung[J].AmJRespirCellMolBiol,1992,6(2):235-243.[4]YAMAMOTOH,KUNOY,SUQIMOTOS,etal.Surface2modi2fiedPLGAnanospherewithchitosanimprovedpulmonarydeliveryofcalcitoninbymucoadhesionandopeningoftheintercellulartightjunctions[J].JControlRelease,2005,102(2):373-381.[5]SHARMAA,SHARMAS,KHULLERGK.Lectin2functional2izedpoly(lactide2co2glycolide)nanoparticlesasoral/aerosolizedantituberculardrugcarriersfortreatmentoftuberculosis[J].JAntimicrobChemother,2004,54(4):761-766.[6]VAUGHNJM,MCCONVILLEJT,BURGESSD,etal.Singledoseandmultipledosestudiesofitraconazolenanoparticles[J].EurJPharmBiopharm,2006,63(2):95-102.[7]ZAHOORA,SHARMAS,KHULLERGK,etal.Inhalablealg2inatenanoparticlesasantituber2culardrugcarriersagainstexperi2mentaltuberculosis[J].IntJAntimicrobAgents,2005,26(4):298-303.[8]TSAPISN,BENNETTD,JACKSONB,etal.Trojanparticles:largeporouscarriersofnanoparticlesfordrugdelivery[J].ProcNatlAcadSciUSA,2002,99(19):12001-12005.[9]HADINOTOK,ZHUK,TANRB.Drugreleasestudyoflargehollownanoparticulateaggregatescarrierparticlesforpulmonarydelivery[J].IntJPharm,2007,341(122):195-206.[10]GRENHAA,SEIJOB,REMUS#N2LdPEZC.Microencapsula2tedchitosannanoparticlesforlungproteindelivery[J].EurJPharmSci,2005,25(425):427-437.[11]GRENHAA,REMUS#N2LdPEZC,CARVALHOEL,etal.Microspherescontaininglipid/chitosannanoparticlescomplexesforpulmonarydeliveryoftherapeuticproteins[J].EurJPharmBiopharm,2008,69(1):83-93.[12]HADINOTOK,ZHUK,TANRB.Drugreleasestudyoflargehollownanoparticulateaggregatescarrierparticlesforpulmonarydelivery[J].IntJPharm,2007,341(122):195-206.[13]COOKRO,PANNURK,KELLAWAYIW.Novelsustainedre2leasemicrospheresforpulmonarydrugdelivery[J].JControlRe2lease,2005,104(1):79-90.[14]EMAMIJ,HAMISHEHKARH,NAJAFABADIAR,etal.Par2ticlesizedesignofPLGAmicrospheresforpotentialpulmonarydrugdeliveryusingresponsesurfacemethodology[J].JMicroen2capsul,2008,25(128):aheadofprint.[15]BLANCOMD,SASTRERL,TEIJdNC,etal.52Fluorouracil2loadedmicrospherespreparedbyspray2dryingpoly(D,L2lactide)andpoly(lactide2co2glycolide)polymers:characterizationanddrugrelease[J].JMicroencapsul,2005,22(6):671-682.[16]HITZMANCJ,ELMQUISTWF,WIEDMANNTS.Developmentofarespirable,sustainedreleasemicrocarrierfor52fluorouracilII:Invitroandinvivooptimizationoflipidcoate