ChineseJournalofPharmaceuticals2015,4666391*250012R944.9A1001-8255201506-0639-08DOI10.16522/j.cnki.cjph.2015.06.0222014-08-141990Tel015098770113E-mailduanyuwei1027@163.com1967Tel0531-88382015E-mailprofessorgxzhai@126.comProgressofPreparationMethodsofHollowMicrospheresDUANYuwei,YUAihua,ZHAIGuangxi*Dept.ofPharmaceutics,CollegeofPharmacy,ShandongUniversity,Jinan250012ABSTRACT:Duetolargefractionofvoidsininnerspace,hollowmicrospherespossessspecialphysicochemicalpropertiesoflargesurfaceareaandgoodthermalstabilityetc.Hollowmicrospherescanloaddrugsthroughphysicalencapsulationorchemicalbonding.Thepurposeofthispaperistoreviewthepreparationtechnologiesofhollowmicrospheres,suchasspraydryingmethod,templatemethod,self-assemblymethodandhydrothermalroute.Differentwaysofloadingdrugsarealsointroduced.Trendsandprospectsofdevelopmentsandapplicationsofhollowmicrospheresarediscussedintheend.KeyWords:hollowmicrosphere;drugdelivery;preparationtechnology;templatemethod;self-assemblymethod;review2-6SiO2PS7,8910-124ChineseJournalofPharmaceuticals2015,46664011.1213BotGIgG7mIgG1485612800L/h2.5ml/minIgG0.7mm180100151267.4±115.3nm+34.11±2.69mV1.216-18134-1.2.119SiO2PSKraskiewiczPS1PEGTHFPSnervegrowthfactorNGFNGFNGF20PC12NGFYangFe3O4Stöber-TEOSSiO2Fe3O4SiO221-YBO3:Eu3+SiO2DOXDOXSiO2@YBO3:Eu3+DOXSiO2DOX1.2.2ChineseJournalofPharmaceuticals2015,4666419WuTEOSSiO2SiO2KH550NH3+HAuCl4AuDOX238.47±39.08nmDOX/SiO2/Au22/SiO2/AuDOXDOX13FujiwaraTween-80Span-80w/oSiO2NH4HCO3NH4Cl2hTween-80Span-80SiO223NH4HCO3NH4ClSiO2SiO2NH4HCO3SiO2SiO2NH4ClSiO2NH4HCO31.2.3124-26EDTA2728Zhang22921Fig.1Layer-by-layerSelf-assemblyProceduresforPreparingHollowMicrospheresChineseJournalofPharmaceuticals2015,46664222Fig.2SchematicIllustrationofHollowMicrospheresBasedonTwoSchemes1EDTADOXDOX/30DOXTiwari/3924h954724h84312Usov/321.2.4---pHLvLaOHCO3pHNaBF4LaF3LaCO3503hDOXDOXLaF3LaCO33321LaOHCO3NaBF4H+OHCO322LaF3LaCO3pH3H+OHCO32H2OCO2La3+FLaF3pH6.2H+CO32La3+FCO32LaCO3FDOXLaCO3FpH4LaF3DOXGdF3GdOHCO3NaBF4pH34pHpHpHH+FGdOHCO3NaBF4100nmpHFH+GdOHCO3NaBF41.335311,36,37ChineseJournalofPharmaceuticals2015,4666432381.3.1ChiangAAC2-MEAPNIPAAmmPEGAAAC/MEA/PNIPAAm3000BAAC/MEA/PNIPAAm3000/mPEG2000ABMEADOXpH114pH7.4DOXAACPNIPAAm37pH5.0AACAACDOXLi36/PNIPAAmPNIPAAm/PNIPAAm16.31.3.2DaimPEGPAspMEAPAspDIPPAspMEADOX10.5pH537Ting381.43Fig.3SchematicIllustrationforFabricationofHollowMicrospheresviaSelf-assemblyProcessChineseJournalofPharmaceuticals2015,46664439,40ZhuFe3+200nm10DaiCaF2DOX41SKOV3-LiSiO225012hSiO2/42230SiO226025068hSiO21012h14hKangGdOHCO3-DOXGdVO443pHDOXGdVO44422.1Bot14,15Fujiwara232.22711,30,332.3DaiCa2+SiO2Ag+45MohapatraCoFe2O4463ChineseJournalofPharmaceuticals2015,4666452013030321,,,.SiO2J.,2012,2619:250-253.2KhanWS,CaoC,ButtFK,etal.HydrogenstorageandPLpropertiesofnovelCd/CdOshelledhollowmicrospherespreparedunderNH3gasenvironmentJ.IntJHydrogenEnerg,2013,385:2332-2336.3PatilLA,ShindeMD,BariAR,etal.SynthesisofSnO2hollowmicrospheresfromultrasonicatomizationandtheirroleinhydrogensensingJ.MaterSciEngB,2011,1767:579-587.4WangS,WangL,YangT,etal.Porous-Fe2O3hollowmicrospheresandtheirapplicationforacetonesensorJ.JSolidStateChem,2010,18312:2869-2876.5SunYY,LiuYQ,ZhaoGZ,etal.AssemblyofsilvernanoparticlesintohollowspheresusingEuCompoundbasedontrifluorothenoyl-acetoneJ.NanoscaleResLett,2008,32:82-86.6XuJ,DongY,CaoJ,etal.Microwave-incorporatedhydrothermalsynthesisofurchin-likeNiOH2CoOH2hollowmicrospheresandtheirsupercapacitorapplicationsJ.ElectrochimActa,2013,114:76-82.7MetaxaAF,EfthimiadouEK,BoukosN,etal.Hollowmicrospheresbasedon-folicacidmodified-hydroxypropylcelluloseandsyntheticmulti-responsivebio-copolymerfortargetedcancertherapy:controlledreleaseofdaunorubicin,invitroandinvivostudiesJ.JColloidInterfaceSci,2014,435:171-181.8DongF,GuoW,ChuSW,etal.Novelfluorinatedpoly-silsesquioxanehollowspheres:synthesisandapplicationindrugreleaseJ.ChemCommunCamb,2010,4640:7498-7500.9,,.SiO2J.,2014,115:25-30.10ZhuY,LeiJ,TianY.Uniformironoxidehollowspheresforhigh-performancedeliveryofinsolubleanticancerdrugsJ.DaltonTrans,2014,4319:7275-7281.11ChiangWH,HoVT,HuangWC,etal.Dualstimuli-responsivepolymerichollownanogelsdesignedascarriersforintracellulartriggereddrugreleaseJ.Langmuir,2012,2842:15056-15064.12LiuC,YaoW,ZhangL,etal.Cell-penetratinghollowspheresbasedonmilkproteinJ.ChemCommunCamb,2010,4640:7566-7568.13,,.J.,2005,1910:19-22.14BotAI,TararaTE,SmithDJ,etal.Novellipid-basedhollow-porousmicroparticlesasaplatformforimmunoglobulindeliverytotherespiratorytractJ.PharmRes,2000,173:275-283.15,,,./J.,2012,1616:2917-2921.16HuangJ,SongYH,ShengY,etal.Gd2O2S:Eu3+andGd2O2S:Eu3+/Gd2O2Shollowmicrospheres:SolvothermalpreparationandluminescencepropertiesJ.JAlloyCompd,2012,532:34-40.17SawantSY,PawarRR,SomaniRS,etal.FacilehardtemplateapproachforsynthetichectoritehollowmicrospheresJ.MaterLett,2014,128:121-124.18WangH,PengL,HuangZX,etal.Well-dispersedhollowsilicamicrospheressynthesiswithsilicasolasprecursorbytemplatemethodJ.JMolStruct,2014,1059:15-19.19,,.—··M.:,2007:260-261.20KraskiewiczH,BreenB,SargeantT,etal.Assemblyofprotein-bas