nanotechnology-based-drug-delivery納米藥物遞送

NanotechnologyBasedDrugDelivery

Dr.BasavarajK.NanjwadeM.Pharm.,Ph.DAssociateProfessorDepartmentofPharmaceuticsJNMedicalCollegeKLEUniversityBelgaum-59001020/03/20191Dept.ofPharmaceuticsNanotechnologyBasedDrugDeliApplicationsofNanotechnology20/03/20192Dept.ofPharmaceuticsApplicationsofNanotechnologyTargetedDrugDelivery20/03/20193Dept.ofPharmaceuticsTargetedDrugDelivery20/03/20NanoparticlesforDrugDeliveryMetal-basednanoparticlesLipid-basednanoparticlesPolymer-basednanoparticlesBiologicalnanoparticles20/03/20194Dept.ofPharmaceuticsNanoparticlesforDrugDeliverNanobiopharmaceuticalsInbiopharmaceuticals,inadditiontothemaintechnologiescovered-liposomal,monoclonalantibody-based,andpolymer-basedtechnologieshostofnewertechnologiessuchasnanoparticlesincludingvariousnanodimensionalentitiessuchasmolecularimprintedpolymers,metallofullerenes,prodrugdelivery,oral,injectableandimplantable,pulmonary,andtransdermalandtransmucosaldeliveryhavecomeup.20/03/20195Dept.ofPharmaceuticsNanobiopharmaceuticalsInbiophDrugDeliveryTechnologyImportanttoPharmaIndustryDrugdeliveryformulationsinvolvelowcostresearchcomparedthatfordiscoveryofnewmolecule,Minimizingthedrugusewouldsignificantlyreducetheeffectivecostofdrugwhichwouldgivefinancialrelieftothepatients,20/03/20196Dept.ofPharmaceuticsDrugDeliveryTechnologyImporDeliverysystemsincreasecommercialopportunitybydistinguishingadrugfromcompetitivethreatsposedby“metoo”drugsandNovelmeansofdeliveryparticularlyusingnano-carriers,canallowbrandeddrugstoberescuedfromabyssofgenericcompetition(maybecalled“resurrectionofdrug”).DrugDeliveryTechnologyImportanttoPharmaIndustry20/03/20197Dept.ofPharmaceuticsDeliverysystemsincreasecommSOMESIGNIFICANTACHIEVEMENTSOFNANODEVICESDevelopmentofonedoseadayciprofloxacinusingnanotechnologyTumortargetedtaxoldeliveryusingnanoparticlesinPhase2clinicaltrialstageImprovedophthalmicdeliveryformulationusingsmarthydrogelnanoparticlesOralinsulinformulationusingnanoparticlescarriers.LiposomalbasedAmphotericinBformulation20/03/20198Dept.ofPharmaceuticsSOMESIGNIFICANTACHIEVEMENTSCHALLENGESPreventionofdrugfrombiologicaldegradationEffectiveTargetingPatientComplianceCosteffectivenessProductlifeextension20/03/20199Dept.ofPharmaceuticsCHALLENGES20/03/20199Dept.ofPRIORITYAREASCancerNanotechnology(i)DiagnosisusingQuantumDots (ii)TumorTargetedDelivery(iii)Imaging(iv)CancerGeneTherapy20/03/201910Dept.ofPharmaceuticsPRIORITYAREASCancerNanotechnPRIORITYAREASDNAVaccinesforparasitic,bacterialandviraldiseasesOralandpulmonaryroutesforsystemicdeliveryofproteinsandpeptidesNanotechnologyinTissueEngineering20/03/201911Dept.ofPharmaceuticsPRIORITYAREAS20/03/201911DeptDrugDeliveryCarriers20/03/201912Dept.ofPharmaceuticsDrugDeliveryCarriers20/03/20TargetingLigands20/03/201913Dept.ofPharmaceuticsTargetingLigands20/03/201913DLiposome's20/03/201914Dept.ofPharmaceuticsLiposome's20/03/201914Dept.oLiposome'sTheirexteriorlipidbilayerisverychemicallyreactive,therebyprovidingameanstoconvenientlycouple“tags”onacovalentbasis.

Such“tags”canbeantibodies,antigens,cellreceptors,nucleicacidprobes,etc.

Thisprovidessignificantversatilityinassayformats(i.e.,immunoassay,receptor-based,nucleicacidprobe,etc.)possible.

With

diametersranginginsizefromapproximately50nmto800nm,theiraqueouscoreencapsulatesuptomillionsofmoleculesofsignalgenerating“markers”thatcanbedetectedinavarietyofdifferentway.

Avarietyofdifferentencapsulantsarepossibleincludingvisuallydetectabledyes(sincethelipidbilayeristransparent),opticallyandfluorometricallydetectabledyes,enzymes,andelectroactivecompounds.

Thisprovidessignificantversatilityinthedetectionschemespossible.20/03/201915Dept.ofPharmaceuticsLiposome's20/03/201915Dept.ofNiosomes20/03/201916Dept.ofPharmaceuticsNiosomes20/03/201916Dept.ofPNiosomesNiosomes,non-ionicsurfactantvesicles,arewidelystudiedasanalternativetoliposomesThesevesiclesappeartobesimilartoliposomesintermsoftheirphysicalpropertiesTheyarealsopreparedinthesamewayandunderavarietyofconditions,fromunilamellarormultilamellarstructures.Niosomesalleviatethedisadvantagesassociatedwithliposomes,suchaschemicalinstability,variablepurityofphospholipidsandhighcost.TheyhavethepotentialforcontrolledandtargateddrugdeliveryNiosomesenhancedthepenetrationofdrugs20/03/201917Dept.ofPharmaceuticsNiosomesNiosomes,non-ionicsuNanopowder20/03/201918Dept.ofPharmaceuticsNanopowder20/03/201918Dept.ofNanopowderNanopowdersarepowderscomposedofnanoparticles,thatisparticleshavinganaveragediameterbelow50nanometers(nm).Ajarofatruenanopowderwhenemptiedfromchestheighttotowardthefloorwilldisperseintotheairbeforereachingthefloor.Mostmanufacturersof“nanopowders”producemicropowderassembliesofnanoparticlesbutthepowderitselfisrarelyananopowder.Suchcompoundshavetwoormoredifferentcations(positivelychargedelements)intheirchemicalformula.Anexampleofacomplexcompoundiscalciumtitanate(CaTiO3).

20/03/201919Dept.ofPharmaceuticsNanopowderNanopowdersarepowdNanocluster20/03/201920Dept.ofPharmaceuticsNanocluster20/03/201920Dept.oNanoclusterOneofthecentralthemesinnanoscienceresearchistosynthesizehighqualitynanoparticleswithprecisecontroloverparticlesize,shape,structure,andcomposition.Forinorganicnanoparticles(e.g.metalandsemiconductor),tworegimesareofparticularinterest,thatis,nanoclustersinasizerangefromsubnanometerto~2nmandnanocrystals(typically2-100nm).20/03/201921Dept.ofPharmaceuticsNanoclusterOneofthecentralNanocrystals20/03/201922Dept.ofPharmaceuticsNanocrystals20/03/201922Dept.NanocrystalsWhenthesizeofthematerialisreducedtolessthan100nanometers,therealmofquantumphysicstakesoverandmaterialsbegintodemonstrateentirelynewproperties.Nano-designofdrugsbyvarioustechniqueslikemilling,highpressurehomogenization,controlledprecipitationetc.,areexploredtoproduce,drugnanocrystals,nanoparticles,nanoprecipitates,nanosuspensions(whichforeaseofunderstandingcommonlymentionedasnanocrystals).

Asdecreasedsizewillincreasethesolubilityofdrugshence,thistechnologyisexploredtoincreaseoralbioavailabilityofsparinglywatersolubledrugs.

20/03/201923Dept.ofPharmaceuticsNanocrystals20/03/201923Dept.Micelle

20/03/201924Dept.ofPharmaceuticsMicelle20/03/201924Dept.ofPMicelleMicelleisanaggregateofamphipathicmoleculesinwater,withthenonpolarportionsintheinteriorandthepolarportionsattheexteriorsurface,exposedtowater.Amphiphilicmoleculesformmicelleaboveaparticularconcentrationwhichiscalledascriticalmicellarconcentration(CMC).

Micellesareknowntohaveananisotropicwaterdistributionwithintheirstructure,means

waterconcentrationdecreasesfromthesurfacetowardsthecoreofthemicelle,withacompletelyhydrophobic(water-excluded)core.Hydrophobicdrugscanbeencapsulated/solubalized,intoinnercore.Thespatialpositionofasolubilizeddruginamicellewilldependonitspolarity,nonpolarmoleculeswillbesolubilizedinthemicellarcore,andsubstanceswithintermediatepolaritywillbedistributedalongthesurfactantmoleculesincertainintermediate

positions.

20/03/201925Dept.ofPharmaceuticsMicelle20/03/201925Dept.ofPhDendrimers20/03/201926Dept.ofPharmaceuticsDendrimers20/03/201926Dept.oDendrimersThesebranchedmacromoleculesareconstructedaroundasimplecoreunit.Dendrimershaveahighdegreeofmolecularuniformity,narrowmolecularweightdistribution,specificsizeandshapecharacteristics,andahighly-functionalized

terminalsurface.Themanufacturingprocessisaseriesofrepetitivesteps

startingwithacentralinitiatorcore.Eachsubsequentgrowthsteprepresentsanew"generation"ofpolymerwithalargermoleculardiameter,twicethenumberofreactivesurfacesites,andapproximatelydoublethemolecularweightoftheprecedinggeneration.

20/03/201927Dept.ofPharmaceuticsDendrimers20/03/201927Dept.ofPolymericNanoparticles20/03/201928Dept.ofPharmaceuticsPolymericNanoparticles20/03/PolymericNanoparticlesInrecentyears,biodegradablepolymericnanoparticleshaveattractedconsiderableattentionaspotentialdrugdeliverydevicesinviewoftheirapplicationsindrugtargetingtoparticularorgans/tissues,ascarriersofDNA

ingenetherapy,andintheirabilitytodeliverproteins,peptidesandgenes

throughaperoralrouteofadministration.20/03/201929Dept.ofPharmaceuticsPolymericNanoparticles20/03/2Carbon6020/03/201930Dept.ofPharmaceuticsCarbon6020/03/201930Dept.ofCarbon60C60aresphericalmoleculesabout1nmindiameter,comprising60carbonatoms

arrangedas20hexagonsand12pentagons:theconfigurationofafootball.HencetheyfindapplicationasNanoPharmaceuticalswithlargedrugpayloadintheircagelikestructure.OntheotherhandwithdevelopmentofvariouschemicalsubstitutesforC60,itispossibletodevelopfunctionalizedC60withbetterdrugtargetingproperties20/03/201931Dept.ofPharmaceuticsCarbon6020/03/201931Dept.ofCarbonNanotube20/03/201932Dept.ofPharmaceuticsCarbonNanotube20/03/201932DepCarbonNanotubeCarbonnanotubesareadeptatenteringthenucleiofcellsandmayonedaybeusedtodeliverdrugsandvaccines.Themodifiednanotubeshavesofaronlybeenusedtoferryasmallpeptideintothenucleioffibroblastcells.Buttheresearchersarehopefulthatthetechniquemayonedayformthebasisfornewanti-cancertreatments,genetherapiesandvaccines.

20/03/201933Dept.ofPharmaceuticsCarbonNanotube20/03/201933DepEquipmentsforNanoparticlesHomogenizerUltraSonicatorMillsSprayMillingSupercriticalFluidTechnologyElectrosprayUltracentrifugationNanofiltration20/03/201934Dept.ofPharmaceuticsEquipmentsforNanoparticlesHoHomogenizer&UltraSonicator

20/03/201935Dept.ofPharmaceuticsHomogenizer&UltraSonicatorMethodsofDrugDelivery20/03/201936Dept.ofPharmaceuticsMethodsofDrugDelivery20/03/THANKYOUE-mail:bknanjwadeyahoo.co.in20/03/201937Dept.ofPharmaceuticsTHANKYOUE-mail:bknanjwadeyaNanotechnologyBasedDrugDelivery

Dr.BasavarajK.NanjwadeM.Pharm.,Ph.DAssociateProfessorDepartmentofPharmaceuticsJNMedicalCollegeKLEUniversityBelgaum-59001020/03/201938Dept.ofPharmaceuticsNanotechnologyBasedDrugDeliApplicationsofNanotechnology20/03/201939Dept.ofPharmaceuticsApplicationsofNanotechnologyTargetedDrugDelivery20/03/201940Dept.ofPharmaceuticsTargetedDrugDelivery20/03/20NanoparticlesforDrugDeliveryMetal-basednanoparticlesLipid-basednanoparticlesPolymer-basednanoparticlesBiologicalnanoparticles20/03/201941Dept.ofPharmaceuticsNanoparticlesforDrugDeliverNanobiopharmaceuticalsInbiopharmaceuticals,inadditiontothemaintechnologiescovered-liposomal,monoclonalantibody-based,andpolymer-basedtechnologieshostofnewertechnologiessuchasnanoparticlesincludingvariousnanodimensionalentitiessuchasmolecularimprintedpolymers,metallofullerenes,prodrugdelivery,oral,injectableandimplantable,pulmonary,andtransdermalandtransmucosaldeliveryhavecomeup.20/03/201942Dept.ofPharmaceuticsNanobiopharmaceuticalsInbiophDrugDeliveryTechnologyImportanttoPharmaIndustryDrugdeliveryformulationsinvolvelowcostresearchcomparedthatfordiscoveryofnewmolecule,Minimizingthedrugusewouldsignificantlyreducetheeffectivecostofdrugwhichwouldgivefinancialrelieftothepatients,20/03/201943Dept.ofPharmaceuticsDrugDeliveryTechnologyImporDeliverysystemsincreasecommercialopportunitybydistinguishingadrugfromcompetitivethreatsposedby“metoo”drugsandNovelmeansofdeliveryparticularlyusingnano-carriers,canallowbrandeddrugstoberescuedfromabyssofgenericcompetition(maybecalled“resurrectionofdrug”).DrugDeliveryTechnologyImportanttoPharmaIndustry20/03/201944Dept.ofPharmaceuticsDeliverysystemsincreasecommSOMESIGNIFICANTACHIEVEMENTSOFNANODEVICESDevelopmentofonedoseadayciprofloxacinusingnanotechnologyTumortargetedtaxoldeliveryusingnanoparticlesinPhase2clinicaltrialstageImprovedophthalmicdeliveryformulationusingsmarthydrogelnanoparticlesOralinsulinformulationusingnanoparticlescarriers.LiposomalbasedAmphotericinBformulation20/03/201945Dept.ofPharmaceuticsSOMESIGNIFICANTACHIEVEMENTSCHALLENGESPreventionofdrugfrombiologicaldegradationEffectiveTargetingPatientComplianceCosteffectivenessProductlifeextension20/03/201946Dept.ofPharmaceuticsCHALLENGES20/03/20199Dept.ofPRIORITYAREASCancerNanotechnology(i)DiagnosisusingQuantumDots (ii)TumorTargetedDelivery(iii)Imaging(iv)CancerGeneTherapy20/03/201947Dept.ofPharmaceuticsPRIORITYAREASCancerNanotechnPRIORITYAREASDNAVaccinesforparasitic,bacterialandviraldiseasesOralandpulmonaryroutesforsystemicdeliveryofproteinsandpeptidesNanotechnologyinTissueEngineering20/03/201948Dept.ofPharmaceuticsPRIORITYAREAS20/03/201911DeptDrugDeliveryCarriers20/03/201949Dept.ofPharmaceuticsDrugDeliveryCarriers20/03/20TargetingLigands20/03/201950Dept.ofPharmaceuticsTargetingLigands20/03/201913DLiposome's20/03/201951Dept.ofPharmaceuticsLiposome's20/03/201914Dept.oLiposome'sTheirexteriorlipidbilayerisverychemicallyreactive,therebyprovidingameanstoconvenientlycouple“tags”onacovalentbasis.

Such“tags”canbeantibodies,antigens,cellreceptors,nucleicacidprobes,etc.

Thisprovidessignificantversatilityinassayformats(i.e.,immunoassay,receptor-based,nucleicacidprobe,etc.)possible.

With

diametersranginginsizefromapproximately50nmto800nm,theiraqueouscoreencapsulatesuptomillionsofmoleculesofsignalgenerating“markers”thatcanbedetectedinavarietyofdifferentway.

Avarietyofdifferentencapsulantsarepossibleincludingvisuallydetectabledyes(sincethelipidbilayeristransparent),opticallyandfluorometricallydetectabledyes,enzymes,andelectroactivecompounds.

Thisprovidessignificantversatilityinthedetectionschemespossible.20/03/201952Dept.ofPharmaceuticsLiposome's20/03/201915Dept.ofNiosomes20/03/201953Dept.ofPharmaceuticsNiosomes20/03/201916Dept.ofPNiosomesNiosomes,non-ionicsurfactantvesicles,arewidelystudiedasanalternativetoliposomesThesevesiclesappeartobesimilartoliposomesintermsoftheirphysicalpropertiesTheyarealsopreparedinthesamewayandunderavarietyofconditions,fromunilamellarormultilamellarstructures.Niosomesalleviatethedisadvantagesassociatedwithliposomes,suchaschemicalinstability,variablepurityofphospholipidsandhighcost.TheyhavethepotentialforcontrolledandtargateddrugdeliveryNiosomesenhancedthepenetrationofdrugs20/03/201954Dept.ofPharmaceuticsNiosomesNiosomes,non-ionicsuNanopowder20/03/201955Dept.ofPharmaceuticsNanopowder20/03/201918Dept.ofNanopowderNanopowdersarepowderscomposedofnanoparticles,thatisparticleshavinganaveragediameterbelow50nanometers(nm).Ajarofatruenanopowderwhenemptiedfromchestheighttotowardthefloorwilldisperseintotheairbeforereachingthefloor.Mostmanufacturersof“nanopowders”producemicropowderassembliesofnanoparticlesbutthepowderitselfisrarelyananopowder.Suchcompoundshavetwoormoredifferentcations(positivelychargedelements)intheirchemicalformula.Anexampleofacomplexcompoundiscalciumtitanate(CaTiO3).

20/03/201956Dept.ofPharmaceuticsNanopowderNanopowdersarepowdNanocluster20/03/201957Dept.ofPharmaceuticsNanocluster20/03/201920Dept.oNanoclusterOneofthecentralthemesinnanoscienceresearchistosynthesizehighqualitynanoparticleswithprecisecontroloverparticlesize,shape,structure,andcomposition.Forinorganicnanoparticles(e.g.metalandsemiconductor),tworegimesareofparticularinterest,thatis,nanoclustersinasizerangefromsubnanometerto~2nmandnanocrystals(typically2-100nm).20/03/201958Dept.ofPharmaceuticsNanoclusterOneofthecentralNanocrystals20/03/201959Dept.ofPharmaceuticsNanocrystals20/03/201922Dept.NanocrystalsWhenthesizeofthematerialisreducedtolessthan100nanometers,therealmofquantumphysicstakesoverandmaterialsbegintodemonstrateentirelynewproperties.Nano-designofdrugsbyvarioustechniqueslikemilling,highpressurehomogenization,controlledprecipitationetc.,areexploredtoproduce,drugnanocrystals,nanoparticles,nanoprecipitates,nanosuspensions(whichforeaseofunderstandingcommonlymentionedasnanocrystals).

Asdecreasedsizewillincreasethesolubilityofdrugshence,thistechnologyisexploredtoincreaseoralbioavailabilityofsparinglywatersolubledrugs.

20/03/201960Dept.ofPharmaceuticsNanocrystals20/03/201923Dept.Micelle

20/03/201961Dept.ofPharmaceuticsMicelle20/03/201924Dept.ofPMicelleMicelleisanaggregateofamphipathicmoleculesinwater,withthenonpolarportionsintheinteriorandthepolarportionsattheexteriorsurface,exposedtowater.Amphiphilicmoleculesformmicelleaboveaparticularconcentrationwhichiscalledascriticalmicellarconcentration(CMC).

Micellesareknowntohaveananisotropicwaterdistributionwithintheirstructure,means

waterconcentrationdecreasesfromthesurfacetowardsthecoreofthemicelle,withacompletelyhydrophobic(water-excluded)core.Hydrophobicdrugscanbeencapsulated/solubalized,intoinnercore.Thespatialpositionofasolubilizeddruginamicellewilldependonitspolarity,nonpolarmoleculeswillbesolubilizedinthemicellarcore,andsubstanceswithintermediatepolaritywillbedistributedalongthesurfactantmoleculesincertainintermediate

positions.

20/03/201962Dept.ofPharmaceuticsMicelle20/03/201925Dept.ofPhDendrimers20/03/201963Dept.ofPharmaceuticsDendrimers20/03/201926Dept.oDendrimersThesebranchedmacromoleculesareconstructedaroundasimplecoreunit.Dendrimershaveahighdegreeofmolecularuniformity,narrowmolecularweightdistribution,specificsizeandshapecharacteristics,andahighly-functionalized

terminalsurface.Themanufacturingprocessisaseriesofrepetitivesteps

startingwithacentralinitiatorcore.Eachsubsequentgrowthsteprepresentsanew"generation"ofpolymerwithalargermoleculardiameter,twicethenumberofreactivesurfacesites,andapproximatelydoublethemolecularweightoftheprecedinggeneration.

20/03/201964Dept.ofPharmaceuticsDendrimers20/03/201927Dept.ofPolymericNanoparticles20/03/201965Dept.ofPharmaceuticsPolymericNanoparticles20/03/Polymeric