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DrugDeliverySystem藥物投遞系統生科系04級黃玫璇891672生科系04級許哲源891659生科系04級蕭宏展891631生科系04級楊淳竣891625藥物投遞系統(DrugDeliverySystem)【必要時將必要限度藥物對必要部位之供應】2.市場分析3.公司簡介1.原理目標導向(Target)傳輸(Transport)控釋(ControlledRelease)藥物釋控系統黃玫璇891672藥物釋控系統1.何謂藥物釋控2.發展釋控的優點3.藥物釋控的種類A.DiffusioncontrolledB.ChemicallycontrolledC.Solvent-activatedcontrolled藥物釋控系統1.何謂藥物釋控2.發展釋控的優點3.藥物釋控的種類A.DiffusioncontrolledB.ChemicallycontrolledC.Solvent-activatedcontrolled【藥物釋控】：DrugControlledReleaseSystem將藥物以特殊的化學包覆，讓藥物在某一種狀態(如PH值改變)下適時(ex:延長)適量釋出。這種控釋劑型的技術發展，目前廣泛地應用於一般的製藥化學工業中。藥物釋控系統1.何謂藥物釋控2.發展釋控的優點3.藥物釋控的種類A.DiffusioncontrolledB.ChemicallycontrolledC.Solvent-activatedcontrolledPotentialAdvantagesofControlledReleaseSystems1.maintenanceofdrugsattherapeuticallydesirablelevels2.theabilitytolocalizedrugstotargetorganstominimizesystemiceffects3.improvedpatientcompliance4.protectionfromdegradationfordrugswithshortinvivolifetimes.ControlledReleasevs.SingleDoseTimeConcentrationSingleDosagesControlledReleaseSideEffectsTherapeuticDoseDesiredRange藥物釋控系統1.何謂藥物釋控2.發展釋控的優點3.藥物釋控的種類A.DiffusioncontrolledB.ChemicallycontrolledC.Solvent-activatedcontrolledTypesofControlledReleaseDevices【Diffusioncontrolled】Diffusionthroughmembraneorbulkpolymer【Chemicallycontrolled】˙polymererosion：surfaceerosion,bulkerosion(combinationoferosionanddiffusion)˙pendentchain【Solvent-activatedcontrolled】˙osmotictransportofwaterthroughsemipermeablemembrane˙waterpenetrationintoglassypolymer1.Diffusioncontrolled【Stomach/Intestine–Liquid】【Capsuleedge–Gel】•Biocompatiblepolymer【Capsulecenter–Dry】•Allowsfordelayedrelease△releaseratesaredeterminedbypolymerpropertyandpartitioncoefficientofthedrugtobereleased.△advantage˙drugdiffusesoutofmatrixatdefinedrate△disadvantage˙efficiencyofdiffusionoflargemolecules˙dangerof‘dosedumping’inbarriersystems2.Chemicallycontrolled˙erosion：Surfaceerosion,Bulkerosion△capsuleiserodedbytheacidsinthestomach△advantage˙injectable(microspheres)˙biodegradable(neednotberemovedsurgically)△disadvantage˙difficulttostoponceinjected2.Chemicallycontrolled˙pendentchain△drugiscovalentlyboundtothepolymerandisreleasedbybondscissionowingtowaterorenzymes3.Solvent-activatedcontrolled△theactiveagentisdissolvedordispersedwithinapolymericmatrixandisnotabletodiffusethroughthatmatrix.△advantage˙complexcontrol△disadvantage˙generallymorebulkydevicesandrequireimplantationBiodegradablePolymersApplicationTargetingmoietyforcell891659許哲源Introduction•Forthepastseveraldecades,researchersandclinicianshavebeenusingdrugsandradiationtokilltumorcells.•Thechemotherapyandradiotherapyareonlysemiselectiveformalignantcells.•Incontrast,targetingdrugtherapyhasthepotentialforgreaterspecificity.•Withtheadventofmonoclonalantibody(MoAb)technology,researcherhavebeenabletotargetdifferentagentstotargetcellsmoreeffectively.Pharmacol.Ther.1994,64:127–54EPReffect•TheEnhancedPermeabilityandRetentioneffectintumortissue•Tumorcellsshowahigherdegreeofuptakeofmacromoleculesbyendocytosisthannormalcell.Microvasc.Res.1996,51:327-346Introduction•Immunotoxins(Its)containatargetingmoietyfordeliveryandatoxicmoietyforcytotoxicity.•Thetoxins(plantorbacterialtoxin)arecatalytic,fewerthan10moleculesinthecytosolofatargetcellenoughtobelethal.Pharmacol.Ther.1994,63(3):209–234Schematicpresentationofligand-containing,shieldedDNAcomplexesfortumor-targetedgenetransferJournalofControlledRelease2003,91:173-181TargetingMoiety•ThetargetingagentscurrentlyusedtoconstructITsareMoAbs,growthfactors/cytokines,andsolublereceptors.•MoAbsarethemostfrequentlyused.J.Clin.Immunol.1992,12:391–405TargetingMoietyTargetingMoiety•BispecificantibodiesarenoveltargetingagentsconstructedbylinkingeitherchemicallyorgeneticallytwodifferentFabfragment,onearmofwhichisdirectedagainstatargetcellandtheotheragainsteffectorTcellsorNKcells(e.g.anti-CD22/anti-CD3-RTA).Blood1993,82:2224–34ToxinMoiety•Themostcommonlyusedtoxicmoietiesarederivedfromeitherbacteria[e.g.Pseudomonasexotoxin(PE)ordiptheriatoxin(DT)],orplants(e.g.abrinorricin).ToxinMoiety•Bothtypesoftoxinskillcellsbyinhibitingproteinsynthesis.–Planttoxinsdamage28SrRNA,–BacterialtoxinsinactivateEF-2Ann.Rev.Immunol.1996.14:49–71Linkers•Forinvivotherapy,thetoxicmoietyoftheITmustbecoupledtothetargetingligandsothatitremainsstableinthebloodandtissuesbutisseparatedfromthetargetingdomainforeffectivetranslocationintothecytoplasm.FactorsaffectingthepotencyofanIT•Bindingaffinityofthetargetingmoiety•ThedensityofthetargetAgonthecell•Naturallyinternalizedorinducedtodoso.•Intracellularrouting•MaypromoteproliferationoftargetcellpopulationClinicaltrials•Thefieldofimmnotoxintherapyisinitsinfancy.TodatemostITsarejustenteringPhaseII/IIItrials.•Anti-ITantibodiesweregeneratedinmosttrialsConclusions•Forthetherapyofcancer,ITshaveyieldedhigherresponseratesinPhaseI/IItrialsthansomeofthedrugsusedtoday.•Thegenerationofnewconstructs,combinatorialtherapy,andinthecaseofcancertherapy,treatmentoftumorsthatareamenabletoIT-mediatedkillingwilleventuallyresultineffectivetreatmentprotocols.References•ThrushGR.,LarkLR.,ClinchyBC.,andVitettaES.Immunotoxins:Anupdate.Ann.Rev.Immunol.1