均质Microfluidizer和应用

NanoNano--encapsulationusingencapsulationusingMicrofluidizerMicrofluidizerTMTMTechnologyPlatformTechnologyPlatformT.Panagiotou*¥,S.V.Mesite*,J.G.Auer*andR.J.Fisher***Microfluidics,33OssipeeRd.,Newton,MA02464,USA¥[e-mail]**MassachusettsInstituteofTechnology,ChemicalEngineering,Cambridge,MA02139-USA30OssipeeRoadNewton,MA02464•Internationalcompany-HeadquartersinNewton,Mass.–USA-OfficesinMinnesota,CaliforniaandGermany-DistributorsandrepsinAsia,Europe,AustraliaandTheAmericas•Publiccompany(mfic.ob)•TechnologyacquiredfromArthurD.LittleMicrofluidicsmanufactureshighshearfluidprocessorsthatareusedto:•Reducetheparticlesizeofsuspensionsoremulsionstonanometerlevels–TOPDOWN•Disruptcells•Enableorexpediteratesofchemicalreactionsorphysicalprocessestoproducenanoparticles(MRTtechnology)-BOTTOMUPMicrofluidicsservesavarietyofindustries:PharmaceuticalInjectables,inhalables,parenteralsBiotechCelldisruption,vaccinesChemicalInks,ceramics,polymers,carbonnanotubesCosmeticNutraceuticalomega-3,plantsterols,vitaminsFoodSoymilk,foodcolorings,flavoringsNano-emulsionsandnano-suspensionswithparticlesize50-500nmaretypicalresults.•Microfluidicsoffersthreeplatformsforencapsulationandcontroldeliveryofactives,Nano-emulsions-Liposomes–Polymers•andtwowaystoproducenanoparticles.Bottomup-TopDownTechnologyI.InteractionChamber:TheheartofMicrofluidizer®technologyThematerialisprocessed/mixedasitflowsinsidethemicrochannelsoftheinteractionchamber.•Actualchanneldimensionsproprietary;typicallyintherangeof50-400microns•Materialofthechannelsisaluminaorpoly-crystallinediamond•Chamberstypesare“Z”and“Y”•“Y”–typechambersusedforencapsulationapplicationsHighPressureInletP1HighPressureInletP1LowPressureOutletP2HighShearZoneHighEnergyImpactZoneHighShearZoneP1P1InteractionChamberYTypeSingleSlotInteractionChamberYTypeSingleSlotInteractionChamberYTypeMulti-Slotted™(forscaleup)InteractionChamberYTypeMultiInteractionChamberYTypeMulti--SlottedSlotted™™(for(forscaleupscaleup))HighPressureInletP1HighShearZonesHighPressureInletP1LowPressureOutletP2HighShearZonesHighEnergyImpactZoneP1P1P1P1PrimaryForcesPrimaryForcesShear:Thedeformationoffluidscausedbyinducingadifferentialvelocity.Impact:Theforceofacollision.•Averagevelocitiesinmicrochannelsmayreach500m/s•Changeofvelocitymagnitudeordirectionexposesthefluidtoafairlyuniformhighshearfield.•Highturbulenceinsideamicrolitervolumeisresponsibleformixinginthenanometerlevel.II.Microfluidizer®ProcessorsInletReservoirProductIntensifierPumpPressuresto40,000psiPressureGaugePatentedInteractionChamberCoolingJacketOutletA.StandardMicrofluidizerProcessor“TopDown”ParticleSizeReduction•Applicationsincludenano-emulsions,liposomesanddispersionsB.MicrofluidicsReactionTechnology(MRT)“BottomUp”NanoparticleGenerationThefeedpumpingsystempreciselycontrolstheratioofthereactants•AspectsofMicrofluidizerTechnologyinclude:-Fixedgeometryinteractionchambersfornarrowparticlesizedistributionandguaranteedscale-up-Mixingscalelessthan50nm-Energydissipationexceeding107W/kg•AspectsofMRTInclude:-Uniformstreamsofreactantsatthenanometerlevel-Precisecontrolofmixinglocation-Limitationofsidereactions-MinimizationofmixingpriortoreactionchamberApplications1.PolymersPoly(Epsilon-Caprolactone)NanoparticlesforDrugDelivery•CreatedusingMRTViaSolvent/AntisolventPrecipitation•Medianparticlesize:239nm•Solvent/AntisolventPrecipitation:averagesizeof141nm•Nano-emulsionevaporationaverageparticlesizeof108nm05101520101001000Particlesize(nm)Frequency(intensity%)Nano-emulsionevaporationSolvent/AntisolventCrystallizationPoly(Lactide-co-Glycolide)(PLGA)forDrugDeliveryPrecipitation2.Liposomes•5passesat18,000psiwiththeF20Y(75μm)ChamberBEFOREAFTERParticleSizeDistributionDrugEncapsulationinaLiposome02468101001000Intensity(%)UnloadedLoaded–10mg/mL58nm84nmIntensity(%)10100100086420Diameter(nm)01002003004005000123#ofpassesparticlesize(nm)18,000psi5,000psiDNAEncapsulationinaLiposome•0.1%DNAplasmidswereencapsulatedinsideaPalmitoyloleoylphosphatidylcholineliposome•DNAintactafterprocessing3.Emulsions•AverageparticlesizeAFTER:76nm•31.3vol.%PFOBBEFOREAFTERBEFORE/AFTERPerfluorocarbonEmulsionBEFOREAFTER15passes0p1p2p3p4p5p7p10p15pProcesspressure:18,000psi(1241bar)Chamber:F20Y(75microns)•FinalproductistranslucentCancerDrugNano-EmulsionFishOilEncapsulationFishoilcontainsOmega3fattyacid,whichisanessentialnutrient.Byencapsulatingthefishoil,theundesirabletastecanbereducedsubstanciallyandtheoilisprotectedfromoxidation.•Medianparticlesizeof12%fishoilemulsionafterprocessing:0.163μm•Medianparticlesizeof14%fishoilemulsionafterprocessing:0.119μmUnprocessedAfterprocessing05101520250.011100Particlesize(microns)Frequency(vol.%)Unprocessed12%oil14%oilVegetableOilEncapsulationOnemethodofaddingoilstofoodformulationsistoencapsulatetheoilinamicelle,usingaoilinwateremulsion,andthenremovethewater.Thegoalofthisprocesswastoreducetheamountoffreeoiltolessthan2.45%afterwaterremoval.•Afterprocessing,theamountoffreeoilwas1.94%•Themedi