表阿霉素脂质体的制备与质量评价

[]2007-11-23[](1979-),,,,E2mail:[e-mail],Tel:[phone],,,,,Tel/Fax:[phone],2,3,13(1.,100850;2.,100088;3.,133000)[]:,HPLC:2pH;HPLC;3:;396.1%,98.4%,92.9%;:2pH,[]pH;;;[]R979.1[]A[]100025501(2008)0220165203PreparationandqualitycontrolofepirubicinhydrochlorideliposomesWUYan1,WUCheng2,KANGYan2Min3,MEIXing2Guo13(1.InstituteofPharmacologyandToxicology,AcademyofMilitaryMedicalSciences,Beijing100850,China;2.TheSec2ondArtilleryGeneralHospital,Beijing100088,China;3.CollegeofPharmacy,YanbianUniversity,Yanji,Jilin133000,China)[Abstract]Objectives:Toprepareepirubicinhydrochlorideliposomes(Epi2lip),establishanHPLCmethodforthedeterminationofEPIandtooptimizethemethodfordeterminationofentrapmentefficiency(EE%).Methods:Epi2lipwaspreparedbythinfilm2pHgradientmethod.Sephadex2G50chromatography,theultrafiltrationmethodanddialysismethodwereusedtodetermineEE%ofliposomes.Results:TheEPI2liphadasmallparticlesizeandnarrowsizedistribution.TheEE%ofliposomeswas96.1%,98.4%and92.9%determinedbySephadex2G50chromatography,ultrafiltrationanddial2ysisrespectively.Conclusion:ThethinfilmpHgradientmethodissuitableforpreparationofEpi2lip.TheHPLCmethodissensitiveandaccurate.TheultrafiltrationmethodcandetermineEE%ofliposomesaccuratelyandquickly.[Keywords]pHgradientmethod;epirubicinhydrochloride;liposome;entrapmentefficiency(,epirubicin,EPI),25%,[1]EPI,,,,,,[2],,,,11.1L22130HPLC();RE5299();AvestinC23();(SympatecGmbH);JEM21230();Cintra10e2(GBC);2132(LKBBromma);Z2160M(Herm2lego);WaterProPS(Labconco);MD34(14103,Solarbio);(30103,Minipore);1.2();(56120084322BullAcadMilMedSci,Apr2008;Vol32No298%,Lipoid);();mPEG20002DSPE(Genzyme);DSPG(Lipoid);G250(100300m,Biochemika);,22.1,/,50,pH4.0,15000psi35150nm,pH7.8,40,,,20min,2.22.2.1:VenusilMPC18(4.6mm250mm,5m);(363232,pH2.5);UV227nm;1.0ml/min;20l4.3min,,11HPLC1.;2.2.2.260g/ml,,,2.2.2.11mlEPI1ml1mol/LHCl,5030min,5ml,EPI222.2.2.2EPI1ml,0.05mol/LNaOH5min,5ml,EPI32.2.2.3EPI1ml,752h,5ml,EPI42.2.2.4EPI1ml,4500lx24h,5ml,EPI552.2.3(100g/ml)2.5,2.0,1.0,0.5,0.25,0.05,0.01ml10ml,,,,AC,A=216300C-34525,r2=0.9996;0.125g/ml2.2.42.2.4.120.0,5.0,0.5g/ml(),5,;5d,RSD2%,45d2.2.4.20.2ml,10ml,6.0,1.5,0.15ml,,99.1%,100.9%,100.5%,RSD2%(n=3),2.32.3.150,2%,,,(6)2.3.27,X50149.87nm,X10=111.18nm,X90=661200843226(200000)190.00nm,0.53:(X90-X10)/X5072.3.3,(differentialscanningcalorimetry,DSC),Epi2lipDSC88DSC2.3.43,=/100%[3]2.3.4.1:Sephadex2G50(20cm1.5cm);;1.0ml/min1ml48ml,25ml,HPLC,EE%96.1%(n=3)2.3.4.20.2ml13000r/min5min,HPLC,98.4%(n=3)2.3.4.3[4]2.0ml,50ml,37,6h,HPLC,,EE%92.9%(n=3)3,40%2pH,,2,,,[4]90%pHEpi,pHEPI(pKa8.3)[5],pH,EPI,[6],C18,;,5min,;,[][1]BirtleAJ.Anthracyclinesandcardiotoxicity[J].ClinOncol,2000,12(3):146-152.[2],,,.2[J].,2006,23(10):1191.[3].(2005)E[M].:,2005.[4],,,.[J].,2004,39(12):1018-1022.[5]ArnoldRD,SlackJE,StraubingerRM,etal.Quantificationofbox2orubicinandmetabolitesinratplasmaandsmallvolumetissuesamplesbyliquidchromatography/electrospraytandemmassspec2troscopy[J].JChromatogrBAnalytTechnolBiomedLifeSci,2004,808(2):141-152.[6],,,.[J].,1994,19(2):79-81.()7612,1