基金项目:重大新药创制———“十二五”综合性新药开发大平台,药物新制剂技术平台(2012ZX09301003-001-009)作者简介:李明媛,女,硕士研究生研究方向:药物新技术与新剂型*通讯作者:梅兴国,男,教授,博士生导师研究方向:药物新技术与新剂型Tel/Fax:(010)66932644E-mail:newdds@126.com硫酸长春新碱热敏脂质体的制备和质量评价李明媛,张慧,杨臻博,李晗,梅乐,梅兴国*(军事医学科学院毒物药物研究所,北京100850)摘要:目的制备硫酸长春新碱(vincristine,VCR)热敏脂质体,测定其粒径及体外释药热敏特性,建立脂质体含量、包封率及有关物质的测定方法。方法pH梯度主动载药法制备长春新碱热敏脂质体,激光粒度分析仪测定脂质体粒径;以水为释放介质,分别考察脂质体在37和42℃的释放特性;超滤离心法测定脂质体包封率;HPLC测定脂质体中长春新碱的含量及有关物质。结果长春新碱热敏脂质体的平均粒径为(86±6)nm,37℃几乎不释放,42℃30min内释放约90%;3批样品包封率均高于95%;含量为1.92mg·mL-1,有关物质符合药典要求。结论长春新碱长循环热敏脂质体的制备工艺简单稳定,所制备的脂质体粒径均一,具有明显的热敏特性,包封率高,适于-20℃长期储存。脂质体含量、包封率及有关物质测定方法简便、快速、准确。关键词:硫酸长春新碱;热敏脂质体;粒径;热敏特性;包封率;超滤离心;含量;有关物质doi:10.11669/cpj.2014.18.009中图分类号:R944文献标志码:A文章编号:1001-2494(2014)18-1615-05PreperationandQualityEvaluationofVincristineSulfateThermosensitiveLiposomesLIMing-yuan,ZHANGHui,YANGZhen-bo,LIHan,MEILe,MEIXing-guo*(InstituteofPharmacologyandToxicology,AcademyofMilitaryMedicalSciences,Beijing100850,China)ABSTRACT:OBJECTIVETopreparevincristinesulfate(VCR)thermosensitiveliposomes,andevaluateitsparticlesizeandre-leasecharacteristicsinvitroandestablishthemethodsfordeterminationofcontent,entrapmentefficiencyandrelatedsubstances.METHODSpHgradientactivedrug-loadingwasusedtoprepareVCRliposomes;photoncorrelationspectroscopywasusedtodeterminetheparticlesize;theinvitroreleasepropertiesofVCRliposomesin37and42℃waterwerecompared;theentrapmentefficiencyoftheliposomeswasdeterminedbyusingcentrifugalultrafiltration;HPLCwasappliedforthedeterminationofcontentandrelatedsubstances.RESULTSTheaverageparticlesizeofVCRliposomeswas(86±6)nm,andtheliposomeshardlyreleasedat37℃andreleasedabout90%within30minat42℃,showingobviousthermosensitiveproperty;theentrapmentefficienciesfor3batcheswerehigherthan95%;thecontentwas1.92mg·mL-1,withtherelatedsubstanceinlinewiththepharmacopoeiarequirements.CONCLUSIONTheprepa-rationprocessforVCRliposomeissimpleandstable.Theliposomeshavenarrowparticlesizedistributionaswellasobviousthermosensi-tiveproperty,anditalsohashighdrugencapsulationefficiencyandisstableat-20℃inlong-termstorage.Thedeterminationmethodsforthecontent,encapsulationefficiencyandrelatedsubstancesofVCRliposomesaresimple,rapidandaccurate.KEYWORDS:vincristinesulfate;long-circulatingthermosensitiveliposomes;particlesize;thermosensitiveproperty;entrapmentef-ficiency;centrifugalultrafiltration;content;relatedsubstance长春新碱是夹竹桃科植物长春花中提取出的生物碱,通过抑制微管蛋白的聚合影响纺锤体微管的形成,使有丝分裂停止于中期,其抗肿瘤作用约为长春碱的10倍,是急性淋巴细胞性白血病的一线用药,对何杰金氏病、绒毛膜上皮癌、淋巴肉瘤、网状细胞肉瘤、乳腺癌、肾母细胞瘤、卵巢癌、睾丸癌、神经母细胞瘤和恶性黑色素瘤也有疗效[1-2]。美国食品药品监督管理局(FDA)于2012年8月9日已批准硫酸长春新碱脂质体注射液用于费城染色体阴性成人急性淋巴细胞白血病(ALL)的治疗[3]。热敏脂质体又称温度敏感型脂质体(thermos...