LiposomeExtruders
Instrument:GenizerLiposomeExtruders
AKA:ExosomesExtruders,ArtificialCellMembraneExtruders;Liposomes
Preparationdevicesbyextrusion
Advantages:Liposomeextrudersaremainlyusedfortheliposome formulationandachievinguniformsizedistributions.Itisanideal instrumenttogeneratenanoscaleliposomeformulations,andtoprepare exosomesandartificialcellmembranes.Byutilizingthetracked-etched filtermembranes,theliposomeextrudersarecapableofcapturinglarge particles,precipitationandachievingsterilefiltration.
Application:ResearchandDevelopmentfortheliposomaldrugdelivery system,vaccine,genedelivery,andcosmetics
WorkingPrinciples:Aliposomeisaspherical-shapedvesiclecomposedof phospholipidbilayers.Phospholipidbilayersarecriticalcomponentsofcell membranes,withhydrophilicandhydrophobicproperties.Inanaqueous solution,thehydrophobicendstendtobindtoeachother,andspontaneously formsmallsphericalliposomes.Theliposomeextruderisdesignedforthe preparationofliposomes.Itiseasytouse,andhashighprecisionparticle sizecontrolabilitywithnarrowdistributionsandsatisfactoryrepeatability. Sofarithasbeenwidelyusedinthepreparationsofcomplexinjectable liposomeproducts.
Liposomeextrusiontechnologyisemployingthestructuralandperformance characteristicsofliposomalphospholipidbilayers.Whentheoperational temperatureisslightlyabovethephasetransitiontemperatureof phospholipids,thelargevesiclesofliposomeswillpassthrough
Figure1Genedeliveryliposomewithphospholipidbilayers
polycarbonatemembraneswithspecificporesizesbyacertainexternal extrusionforce.Thelargeparticlesizeliposomeormultiplecompartments liposomesarerapidlyrepolymerizedintosmaller-sizeliposomesafterbeing rupturedbytheshearofmembranepores.Sincetheporesizeof polycarbonatemembraneisfixed(e.g.,50nm,100nm,200nm,400nm,1um, etc.),andthepolycarbonateextrusionmembranefeaturesverticaland uniformnanoporedistributionsonthemembranesurface,whenthelarge vesiclespassthroughthemembranewithaspecificnanoporesizeseveral times,thesampleisextrudedtotheuniformsizedecidedbythepore.
1.CommonTypesofLiposomeExtruders
Liposomeextruderscanbeclassifiedintothreecategories:hand drivenliposomeextruders,jacketedliposomeextruders,andonlineliposome extruders.Eachcategoryisbasedonitsdifferentpowersources.
1.1HandDrivenLiposomeExtruders
Thehanddrivenliposomeextrudersarecapableofprocessingthesample volumefrom0.25mLto2.5mL,whichissuitableforminisamplevolume applicationsduringtheexperimentalphase.Itisoperatedbysimplypushing theplungermanually.Therearetwotypesofhanddrivenextruders: extrudersunderambienttemperature,andextruderswithjacketedoption. Thehanddrivenliposomeextruderswithcoolingjacketaredesignedfor thoseextrusionconditionstocontrolthesampletemperature.
Figure2SchematicdiagramdepictingtheliposomeextrusionThejacketedliposomeextrudershaveawiderangeofprocessingcapacities, fromsamplevolume2mLto3Ldependingonthemodels.Itissuitablefor labscaleandpilotscaleapplications.Itisdrivenbycompressednitrogen cylinder.Mostofthejacketedliposomeextrudersaredesignedwithjacketed barreltoachievethetemperaturecontrolofthesample.
Onlineliposomeextrudersareavailablefortheprocessingcapacityfrom 2mLto20Ldependingonthedifferentmodels.Theseextrudersaremore suitableforpilotscaleapplications.Itispoweredbyahigh-pressurepump unitorotherproductionequipment.
Figure3HandDrivenLiposomeExtruders
1.2JacketedLiposomeExtruders
Figure4JacketedLiposomeExtruders
1.3OnlineLiposomeExtruders
Themultipleliposomeextruderssystemisabletoprocessthevolumefrom 1Lto200L.Itfeaturesboththetemperatureandpressuresensorsinthe productline,andacontrolpaneltocontroltheproductionforliposomes.
Theoperationsofliposomeextrudershavehighrequirementsforthe extrusionmembranes.Thenucleustrack-etchedpolycarbonatemembranes shouldhaveuniformdistributionsoffilterpores.Inanidealmembrane,all nanoporesshouldbeofthesamesize.Furthermore,theextrusion membranewithverticalporedistributionismoreconducivetothe preparationofliposomeextrusion.
Figure5OnlineLiposomeExtruders
1.4MultipleLiposomeExtrudersSystem
Figure6MultipleLiposomeExtruderssystemswithliposomeextrudingcontrolpanel
2.Track-EtchedPolycarbonateExtrusionMembranes
Figure7MicroscopicRepresentationforTrack-EtchedPolycarbonateMembranes
Ingeneral,selectingrightsizeofthepolycarbonatemembraneswillensure successfulextrusion.Itisstronglyrecommendedtoknowtheinitialparticle sizeoftheprocessingsamplebeforetheextrusion.Anotherfactorto considerforselectingthemembraneisthedesiredparticlesizeforyourend product.Forexample,iftheinitialparticlesizeofthesampleis1μm,and thetargetistoachievetheparticlesizebelow100nm,herearetwooptions available:
1)ExtrusionMultipleTimesviatheTargetPoreSizeMembranes
Forexample,theusercanextrudethesamplethrougha100nm polycarbonatemembraneusingaliposomeextruderseveraltimes.Butthe problemsthatmayariseare:
1)Thedifficultiesinextrusionprocess;
2)Thelargevesiclesmayblockthesurfaceofthepolycarbonate membrane,andrequestareplacementofanewmembrane,etc.
2)ExtrusionviatheDifferentPoreSizeMembranes
Thisprocedureistousedifferentporesizemembranestoextrudestepby step.Forexample,thesampleisextrudedthrougha400nmpolycarbonate membranefirst,andobservetheextrusionprocess.Ifitishardtoextrudethe samplethroughthe400nmmembranes,thenreplaceanewmembranewitha largerporesize,suchas800nmforextrusion3~5times.Itcanbeoptimized duringtheprocess.Afterthefirst-roundextrusion,selectasmallerporesize polycarbonatemembrane,suchas100nmor80nmtoextrudeagain.200 nmpolycarbonatemembranescanbeusedasatransitioniftheextrusionis difficulttogothroughthe100nmmembranes.
3)HighPressureHomogenization-ExtrusionMethod
Thesamplecanbehighpressurehomogenizedfirst,andextrudedthrougha 100nmor80nmpolycarbonatemembraneafterhomogenization.(Figure8)
Figure8HighPressureHomogenizercombineswithonlineliposomeextruder