Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids 英文参考文献.docVIP

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Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids 英文参考文献.doc

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Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids 英文参考文献

FabricationPrinciplesandTheirContributiontothe SuperiorInVivoTherapeuticEfficacyofNano-Liposomes RemoteLoadedwithGlucocorticoids YuvalAvnir1,KerenTurjeman1,DeborahTulchinsky1,AlexSigal1,PabloKizelsztein1,DinaTzemach2, AlbertoGabizon2,YechezkelBarenholz1* 1Laboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University-Hadassah Medical School, Jerusalem, Israel, 2Laboratory of ExperimentalOncology,ShaareZedekMedicalCenter,Jerusalem,Israel Abstract We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (.90%) and stable GC encapsulation was obtained based on a transmembrane calciumacetategradientdrivingtheactiveaccumulationofanamphipathicweakacidGCpro-drugintotheintraliposome aqueouscompartment,whereitformsaGC-calciumprecipitate.Wedemonstratefabricationprinciplesthatderivefromthe physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. Theseprinciplesallowfabricationofformulationsthatexhibiteitherafast,second-order(t ,1h),oraslow,zero-order 1/2 releaserate(t1/2 ,50h)kinetics.Ahightherapeuticefficacywasfoundinmurinemodelsofexperimentalautoimmune encephalomyelitis(EAE)andhematologicalmalignancies. Citation:AvnirY,TurjemanK,TulchinskyD,SigalA,KizelszteinP,etal.(2011)FabricationPrinciplesandTheirContributiontotheSuperiorInVivoTherapeutic EfficacyofNano-LiposomesRemoteLoadedwithGlucocorticoids.PLoSONE6(10):e25721.doi:10.1371/journal.pone.0025721 Editor:DimitrisFatouros,AristotleUniversityofThessaloniki,Greece ReceivedApril16,2011;AcceptedSeptember9,2011;PublishedOctober6,2011 Copyright: ? 2011 Avnir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This study was supported inpart bythe Barenh