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ID:1231686
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时间:2017-11-09
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1、乳铁蛋白-聚合物泡囊载S14G-Humanin肽对Amyloid-β25-35诱导的阿尔茨海默病模型大鼠的神经保护作用俞媛1,冯亮2,高会乐2,蒋新国2*(1第二军医大学药学院药剂学教研室上海200433,2复旦大学药学院药剂学教研室上海200032)摘要:目的构建以乳铁蛋白作为靶向功能基、可生物降解聚合物泡囊为载体的脑靶向递药系统,并对其脑部递药特性作出药效学评价。方法制备载神经肽S14G-Humanin的乳铁蛋白-聚合物泡囊并对其进行表征,建立大鼠阿尔茨海默病模型,采用Morris水迷宫试验
2、评价载药系统对大鼠记忆认知障碍的改善。结果聚合物泡囊粒径约126nm,zeta电位-2.54mV,包封率21.78%,药效学实验表明,载S14G-Humanin的聚合物泡囊能够显著改善大鼠的记忆缺陷,同时对Amyloid-β25-35诱导的Bax蛋白的过量表达具有抑制作用。结论乳铁蛋白连接聚合物泡囊载药系统能够对多肽药物起到保护作用,提高药物的治疗效果,本递药系统具有较好的脑内递药特性。关键词:聚合物泡囊乳铁蛋白阿尔茨海默病中图分类号: 文献标识码: 文章编号:LactoferrinCon
3、jugatedself-assembledPolymervesiclesloadedS14G-Humanin,preventsAmyloid-β25-35inducedmemoryimpairmentinratsYUYuan1,FENGLiang2,GAOHui-le2,JIANGXin-guo2*(1DepartmentofPharmaceutics,SchoolofPharmacy,SecondMilitaryMedicalUniversity,Shanghai200433;2Departm
4、entofPharmaceutics,SchoolofPharmacy,FudanUniversity,Shanghai200032)ABSTRACT:OBJECTIVE Toprepareanovelbraintargetingsystem,lactoferrinconjugatedself-assembledpolymervesicles(Lf-PVs),whichthebraindeliverypropertyhadbeenevaluatedinvivo.METHODSS14G-Human
5、in(S14G-HN)asaneuroprotectivepeptidewasentrappedwithinLactoferrinconjugatedself-assembledpolymervesiclesbyanammoniumsulphategradientsmethod.TheLf-PVswerecharacterizedforshape,size,electricalchargeandentrapmentefficiency.Thevivoeffect12ofLf-PVscontain
6、edS14G-HNwasexaminedonamnesiainducedbyAmyloid-β25-35inrats.RESULTS TheLf-PVshadaroundandvesicle-likeshapewithameandiameteraround126nmbydirectcryogenictemperaturetransmissionelectronmicrograph(Cryo-TEM)andanegativeelectricalcharge(-2.54mV).CouplingofL
7、fwithPVswasconfirmedbyimmuno-goldlabelingofLfvisualizedundertheTEM.Thedrugentrapmentefficiencyis21.78%.S14G-HNencapsulatedintoLf-PVscouldprotectlatentlearningaswellasspatialworkingmemoryandinhibittheover-expressionofBaxproteininAmyloid-β25-35treatedr
8、ats.CONCLUSIONTheLf-PVsmayprovideapromisingcarriertodeliverpeptideacrosstheBBBforthetreatmentofbraininfection.KEYWORDS:polymervesicles;lactoferrin;Alzheimer'sdisease中枢神经系统疾病是危害人类健康的一大类疾病,而血脑屏障(blood-brainbarrieer,BBB)限制了大多数化学药物、多肽药物和基因药物的脑内转运,使药物无法自主
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