长循环脂质化策略增强达托霉素抗耐甲氧西林金葡菌全身感染.pdf

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1、药学学报ActaPharmaceuticaSinica2014，49(5)：701—710·70l·Long—circulatingliposomaldaptomycinenhancesprotectionagainstsystemicmethicillin—resistantStaphylococcusaureusinfectionwithimprovedtherapeuticpotentialHUANGXing—liang，WUJin，SUTing—ting，LIYan—hong，CHENZ

2、hang—bao，LIChong(CollegeofPharmaceuticalSciences，SouthwestUniversity,Chongqing400716,China)Abstract：Inthefaceofescalatingproblemswithpathogencontrol，thedevelopmentofproperformulationsofexistingantibioticsisasimportantasthedevelopmentofnovelantibiotic

3、s．DaptomycinisalipopeptideantibioticwithpotentactivityagainstGram—positivebacteria．Currently,onlyinjectablesolutionofdaptomycinhasbeenapprovedforclinicaluse．Inthepresentstudy,theformulationofPEGylatedliposomaldaptomycin(PLD)waspreparedandoptimized，an

4、ditseficacyagainstmethicillin-resistantStaph~lococcusaureus(MRSA252)strainswasinvestigated．TheobtainedPLDhadameanvesiclediameterof(111．54-15．4)amandameanpercentdrugloadingoff5．814-0．19)％withhighstoragestability．PotentactivityofPLDagainstMRSAwasdemons

5、tratedinvitrowithamoresustainedeffectthanthatofconventionalliposomaldaptomycinanddaptomycinsolution．Inaddition，intravenousadministrationofasingledose(equaltohumanuse)ofPLDsignificantlyincreasedthesurvivalofmiceinaMRSA252systemicinfectionmodelcompared

6、withotherformulations．DrugdistributioninthelungwassignificantlyenhancedfollowingadministrationofPLD，andnomeasurabletissuelesionsorpathologicalchangesweredetectedduringPLDtreatment．Takentogether,PEGylatedliposomesloadedwithdaptomycinmayrepresentapromi

7、singapproachtoreduceMRSA252infections，especiallythoseinvolvingbloodstreamdissemination，suchashematogenouspulmonaryinfection．Keywords：daptomycin；long—circulatingliposome；methicillin—resistantst印hylococcusaureus；systemicinfe：ctionCLCnumber：R917Document

8、code：AArticleID：0513—4870(2014)05-0701-10长循环脂质化策略增强达托霉素抗耐甲氧西林金葡菌全身感染兽／x宣rth吴瑾，苏婷婷，李艳红，陈章宝，李种,~，(西南大学药学院，重庆400716)摘要：随着病原体耐药的控制难度持续增大，除不断研发新型抗生素之外，对已有抗生素进行递送研究与新制剂创制具有同等重要性。达托霉素是近年来上市的一种新型脂肽类抗生素，目前仅有其普通溶液型注射剂用于临床。本文采用聚乙二醇修饰的脂质体作为载体，考察并系统评价经优化制备的长循环达托霉