Activity and Interactions of Liposomal Antibiotics in Presence of Polyanions and Sputum of Patients with Cystic Fibrosis 英文参考文献.docVIP

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Activity and Interactions of Liposomal Antibiotics in Presence of Polyanions and Sputum of Patients with Cystic Fibrosis 英文参考文献.doc

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Activity and Interactions of Liposomal Antibiotics in Presence of Polyanions and Sputum of Patients with Cystic Fibrosis 英文参考文献

ActivityandInteractionsofLiposomalAntibioticsin PresenceofPolyanionsandSputumofPatientswith CysticFibrosis MisaghAlipour1,ZachariasE.Suntres1,2,MajedHalwani1,AliO.Azghani3,AbdelwahabOmri1* 1TheNovelDrugVaccineDeliverySystemsFacility,DepartmentofChemistryandBiochemistry,LaurentianUniversity,Sudbury,Ontario,Canada,2MedicalSciences Division, NorthernOntarioSchoolofMedicine,LakeheadUniversity,ThunderBay,Ontario,Canada,3DepartmentofBiology,UniversityofTexasatTyler,Tyler,Texas, UnitedStatesofAmerica Abstract Background:TocomparetheeffectivenessofliposomaltobramycinorpolymyxinBagainstPseudomonasaeruginosainthe CysticFibrosis(CF)sputumanditsinhibitionbycommonpolyanioniccomponentssuchasDNA,F-actin,lipopolysaccharides (LPS),andlipoteichoicacid(LTA). Methodology: Liposomal formulations were prepared from a mixture of 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) or 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Cholesterol (Chol), respectively. Stability of the formulationsindifferentbiologicalmilieusandantibacterialactivitiescomparedtoconventionalformsinthepresenceof theaforementionedinhibitoryfactorsorCFsputumwereevaluated. Results: The formulations were stable in all conditions tested with no significant differences compared to the controls. Inhibition of antibiotic formulations by DNA/F-actin and LPS/LTA was concentration dependent. DNA/F-actin (125 to 1000mg/L) and LPS/LTA (1 to 1000mg/L) inhibited conventional tobramycin bioactivity, whereas, liposome-entrapped tobramycinwasinhibitedathigherconcentrations-DNA/F-actin(500to1000mg/L)andLPS/LTA(100to1000mg/L).Neither polymyxinBformulationwasinactivatedbyDNA/F-actin,butLPS/LTA(1to1000mg/L)inhibitedthedruginconventional form completely and higher concentrations of the inhibitors (100 to 1000mg/L) was required to inhibit the liposome- entrappedpolymyxinB.Co-incubationwithinhibitoryfactors(1000mg/L)increasedconventional(16-fold)andliposomal(4- fold)tobramycinminimumbactericidalconcentrations(MBCs),whilebothpolymy