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Enhanced effect of liposomeencapsulated amikacin on Mycobacterium aviumM. intracellulare complex infection in beige mice. PubMed.cn
DüzgüneşN,PerumalVK,KesavaluL,GoldsteinJA,DebsRJ,GangadharamPR.
Abstract
Weexaminedthetherapeuticeffectsoffreeandliposome-encapsulatedamikacinonMycobacteriumavium-M.intracellularecomplexinfectionbyusingthebeige-mousemodelofthedisease.Inthefirstseriesofstudies,intravenousadministrationoffourweeklydosesof5mgofamikacinperkgencapsulatedinlarge(approximately0.4-microndiameter),unilamellarliposomesarrestedthegrowthofM.avium-M.intracellularecomplexorganismsintheliver,asmeasuredbyCFUcounts.M.avium-M.intracellularecomplexlevelsinuntreatedanimalsandinthosetreatedwiththesamedoseoffreeamikacinincreasedbyseveralordersofmagnitudeover8weeks.Liposome-encapsulatedamikacinwasalsoeffectiveagainstM.avium-M.intracellularecomplexorganismsinthespleenandkidneys,reducingtheCFUcountsbyabout1,000-foldcomparedwiththoseofbothuntreatedcontrolsandfree-drug-treatedmice.Inthelungs,aslightreductioninCFUwasobservedintheliposome-encapsulated-amikacin-treatedgroup,butonlyatthe8-weekpoint.Neitherfreenorliposome-encapsulatedamikacinreducedthecolonycountsinthelymphnodescomparedwiththoseofcontrolanimals.ReductionsinCFUinallorgansgreaterthanthosecausedbytheliposomepreparationcouldbeachievedbyintramuscularadministrationoffreeamikacin,butonlyata10-fold-higherdosegiven6daysaweekfor8weeks.Inthesecondseriesofstudies,weinvestigatedtheeffectsof(i)doublingthedoseofliposome-encapsulatedamikacinand(ii)increasingthesizeoftheliposomesandprolongingthetreatmenttofiveinjections.Administrationof10mgofamikacinperkginliposomes2to3micrometerindiameterwasmoreeffectiveintheliverthan5or10mgofamikacinperkginliposomes0.2micrometerindiameter.AslightreductionintheCFUlevelsinthelungswasobservedwiththehigherdose,irrespectiveofliposomesize.Ourresultsindicatethatliposome-baseddeliveryofamikacinenhancesitsanti-M.intracellularecomplexactivity,particularlyintheliver,spleen,andkidney,andmaythereforeimprovethetherapyofthisdisease.
PMID:3196002[Pubmed-MEDLINE]
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