多西他赛ph敏感嵌段共聚物胶束的制备及其制剂学研究

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1、*通讯作者Tel：024-23986306，E-mail：chendawei@syphu.edu.cn多西他赛pH敏感嵌段共聚物胶束的制备及其制剂学研究陈大为*，鄢璐，乔明曦，胡海洋，赵秀丽，陈曦，邓意辉（沈阳药科大学药学院药剂系，沈阳110016）摘要：本文在合成pH敏感两亲性嵌段共聚物聚（2-乙基-2-噁唑啉）-聚乳酸（PEOz-PDLLA）的基础上，采用薄膜分散法制备了多西他赛pH敏感嵌段共聚物胶束，利用芘荧光探针技术测定胶束的临界胶束浓度（CMC）；通过高效液相色谱测定胶束的载药量及包封率；分别利用透射电镜、动态光散射法

2、和Zeta电位分析仪对胶束的形态、粒径和表面电位进行了表征；采用透析法考察了载药聚合物胶束的体外释放行为。结果表明，胶束的临界胶束浓度值为1.0×10-3g·L-1；载药量可达15.0%，包封率为91.1%；胶束具有很窄的粒度分布，平均粒径为28.7nm；胶束粒子为圆球形且分散良好，其表面Zeta电位值为（1.19±0.12）mV；在pH7.4释放介质中，多西他赛胶束具有缓释作用；而在pH5.0条件下，胶束释药明显加快，体现出PEOz-PDLLA胶束释药行为的pH敏感性。综合上述研究可见，PEOz-PDLLA嵌段共聚物胶束作为疏

3、水性抗肿瘤药物的给药系统具有很好的应用前景。关键词：多西他赛；pH敏感；嵌段共聚物；胶束；薄膜分散法PreparationStudyofdocetaxel-loadedpH-sensitiveblockcopolymermicellesCHENDa-wei，YANLu，QIAOMing-xi，HUHai-yang，ZHAOXiu-li，CHENXi，DENGYi-hui(DepartmentofPharmaceutics，SchoolofPharmaceuticalSciences，ShenyangPharmaceuticalU

4、niversity，Shenyang，110016，China)ABSTRACT:BasingonthesynthesisofpH-sensitiveamphiphilicblockcopolymerPoly(2-ethyl-2-oxazoline)-Poly(D,L-lactide)(PEOz-PDLLA),thispaperprepareddocetaxel-loadedpH-sensitiveblockcopolymermicellesusingfilmdispersionmethod.TheCriticalMicelle

5、Concentration(CMC)wasmeasuredbyPyreneFluorescentProbeTechnique.Theentrapmentefficiencyanddrug-load10amountweredeterminedbyHPLC.Themorphology,diameterandsurfacepotentialofthemicelleswerecharacterizedbyTransmissionElectronMicroscopy(TEM),DynamicLightScattering(DLS)andZ

6、etapotentialanalyzer,respectively.TheinvitroreleasebehaviorofDTXfrompolymericmicelleswasinvestigatedusingdialysismethod.TheresultsindicatedthattheCMC,drug-loadamountandentrapmentefficiencyofthemicelleswas1.0×10-3g·L-1,15.0%and91.1%,respectively.Themicelleshadanarrows

7、izedistribution,withameandiameterof28.7nm.Themicellewasglobular-shapedanditsZetapotentialwas1.19±0.12mV.InpH7.4PBS,docetaxelwasreleasedinasustainedmannerfromthemicelles;whileinPBSatpH5.0,drugwasreleasedmorerapidly,theseresultssuggestedthepH-sensitivedrugreleasebehavi

8、orofthePEOz-PDLLAmicelles.Accordingtoallthestudiesabove,itcanbeconcludedthatthePEOz-PDLLAblockcopolymermicellesmaybeappliedaspromis