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1、Biomacromolecules2010,11,191519201915ThermosensitiveLiposomesModifiedwithPoly(N-isopropylacrylamide-co-propylacrylicacid)CopolymersforTriggeredReleaseofDoxorubicinTerenceTa,*AnthonyJ.Convertine,ChristopherR.Reyes,PatrickS.Stayton,andTyroneM.PorterDepar
2、tmentofBiomedicalEngineering,BostonUniversity,Boston,Massachusetts02215,DepartmentofBioengineering,UniversityofWashington,Seattle,Washington98195ReceivedMay6,2010;RevisedManuscriptReceivedJune25,2010Anovelpolymer-modifiedthermosensitiveliposome(pTSL)wa
3、sdevelopedforthedeliveryofDoxorubicin(DOX)forcancertherapy.Copolymerscontainingtemperature-responsiveN-isopropylacrylamide(NIPAAm)andpH-responsivepropylacrylicacid(PAA)weresynthesizedviareversibleaddition-fragmentationchaintransfer(RAFT)polymerization
4、,yieldingcopolymerswithdualpH/temperature-dependentphasetransitionproperties.Whenattachedtoliposomes,thesecopolymersweremembrane-disruptiveinapH/temperature-dependentmanner.pTSLdemonstratedenhancedreleaseprofileandsignificantlylowerthermaldosethresholdw
5、hencomparedtotraditionalthermosensitiveformulationsandwerestableinserumwithminimaldrugleakageovertime.Theseliposomesthushavethepotentialtodramaticallyreducetheriskofdamagetohealthytissuesthatisnormallyassociatedwithliposomalcancertherapy.1,2Introducti
6、oncontainingthermosensitiveliposomes(LTSL).Lysolipidsfa-cilitatetheformationofdefectsandmembraneopeningsduringThermosensitiveliposomes(TSL)areapromisingandthephasetransition,increasingbilayerpermeabilityandcausingextensivelystudiedclassofliposomeswith
7、tunabledrugrelease3,4rapiddrugrelease.However,lysolipidshavebeenshowntoproperties.TSLarecomposedoflipidbilayersthatundergo4rapidlydesorbfromthebilayer,likelyresultinginlossoftemperature-dependentphasetransitionsfromgeltoliquidphasetemperature-sensitiv
8、ityandinstabilityinvivo.Indeed,prematureandarepermeableatelevatedtemperatures,resultinginrapid1,2leakageofdruginvivo(50%ofencapsulateddrugat37°Creleaseofencapsulateddruguponheating.TSLsystems56within5min,∼70%within1h)hasbeenobserved.designedfo
