PEG Minocycline-Liposomes Ameliorate CNS Autoimmune Disease 英文参考文献.docVIP

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PEG Minocycline-Liposomes Ameliorate CNS Autoimmune Disease 英文参考文献.doc

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PEG Minocycline-Liposomes Ameliorate CNS Autoimmune Disease 英文参考文献

PEGMinocycline-LiposomesAmeliorateCNS AutoimmuneDisease WeiHu1.,JosbertMetselaar2.,Li-HongBen1,PetraD.Cravens1,MahendraP.Singh1,ElliotM. Frohman1,3,ToddN.Eagar1,4,MichaelK.Racke5,BerndC.Kieseier6*,OlafStu¨ve1,4,6,7* 1DepartmentofNeurology,UniversityofTexasSouthwesternMedicalCenteratDallas,Dallas,Texas,UnitedStatesofAmerica,2DepartmentofPharmaceutics,Utrecht InstituteforPharmaceuticalSciences,UtrechtUniversity,Utrecht,TheNetherlands,3DepartmentofOphthalmology,UniversityofTexasSouthwesternMedicalCenterat Dallas, Dallas, Texas, United States of America, 4Center for Immunology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America,5DepartmentofNeurology,OhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica,6DepartmentofNeurology,HeinrichHeineUniversity,Du¨sseldorf, Germany,7NeurologySection,VANorthTexasHealthCareSystem,MedicalService,Dallas,Texas,UnitedStatesofAmerica Abstract Background: Minocycline is anoral tetracycline derivative withgood bioavailability in the central nervous system (CNS). Minocycline, a potent inhibitor of matrix metalloproteinase (MMP)-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Potential adverse effects associated withlong-termdailyminocyclinetherapyinhumanpatientsareconcerning.Here,weinvestigatedwhetherlessfrequent treatmentwithlong-circulatingpolyethyleneglycol(PEG)minocyclineliposomesareeffectiveintreatingEAE. Findings:PerforminginvitrotimekineticstudiesofPEGminocycline-liposomesinhumanperipheralbloodmononuclear cells(PBMCs),wedeterminedthatPEGminocycline-liposomepreparationsstabilizedwithCaCl2areeffectiveindiminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantlyreducedthenumberofCNS-infiltratingleukocytes,andtheo