三嵌段氧化还原/pH双重响应型载药胶束的制备及性能研究  

Preparation and Properties of Redox and pH Dual Responsive Triblock DOX-loaded Polymeric Micelles

作　　者：张丹[1] 苑莹芝 马敏[1] 袁建超[1] Zhang Dan Yuan Yingzhi Ma Min Yuan Jianchao(College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, Chin)

机构地区：[1]西北师范大学化学化工学院,甘肃兰州730070

出　　处：《广东化工》2016年第22期30-32,共3页Guangdong Chemical Industry

基　　金：国家自然科学基金资助项目(21364011;20964003)

摘　　要：以含有缩醛键的端羟基聚己内酯(HO-PCL-Acetal-OH)和含有二硫键的端羧基聚乙二醇(PEG-SS-COOH)反应形成两亲性三嵌段共聚物PEG-SS-PCL-Acetal-SS-PEG。该嵌段共聚物在水溶液中自组装,形成了具有核壳结构的胶束纳米粒子。采用核磁共振谱(1H NMR)来表征嵌段共聚物的结构,用动态光散射(DLS)和透射电子显微镜(TEM)表征纳米粒子的尺寸和形貌。此外,通过DLS分别检测胶束在二硫苏糖醇(DTT)/p H=5.0和p H=7.4溶液中粒径的变化,结果证明在含有DTT和弱酸性的条件下,由于三嵌段共聚物胶束的二硫键/缩醛键断裂,使其负载有抗癌药物阿霉素(DOX)的胶束溶胀,粒径变大,药物快速释放。药物体外释放模拟结果表明,在p H 5.0、DTT/p H 7.4和DTT/p H 5.0的情况下,DOX 24小时的累积释放率分别为:40.07%、92.05%和95.36%,但是在p H=7.4时释放率仅为25.17%。在37℃条件下,这些载药纳米粒子表现出具有氧化还原/p H双重响应性的药物释放行为。Amphiphilic triblock copolymer polyethylene glycol-SS-poly（ε-caprolactone）-Acetal-SS-polyethylene glycol （PEG-SS-PCL-Acetal-SS-PEG） was synthesized by the reaction of hydroxyl terminated PCL containing acetal bond （HO-PCL-AcetaI-OH） and carboxyl terminated PEG bearing disulfide bond （PEG-SS-COOH）. The block copolymer self-assembled into nanosized micelles in aqueous solution with core-shell structure. It was characterized by IHNMR. The size and morphology of the nanosized micelles were characterized by dynamic light scattering （DLS） and transmission electron microscopy （TEM）. The size changes of micelles were detected by DLS at dithiothreitol （DTT） and/or pH 5.0 solutions. The results showed that DOX-loaded micelles swelled, particle size became large and DOX was released fast due to disulfide/acetal bond of cleavage of ampbiphilic triblock copolymer micelles under conditions of containing weak acid and DTT. The in vitro release results （measured by UV/vis spectroscopy） indicated that 40.07 %, 92.05 % and 95.36 % of DOX released from DOX-loaded PEG-SS -PCL-Acetal-SS-PEG micelles at pH=5.0, DTT/pH=7.4 and DTT/pH=5.0 in 24 h, respectively; However, only 25.17 % of DOX were released from DOX-loaded PEG-SS-PCL-Acetal-SS-PEG micelles at pH=7.4 in 24 h. The DOX-loaded micelles showed redox and pH dual responsive drug release behavior at 37 ℃.

关 键 词：聚合物胶束 三嵌段共聚物 氧化还原响应 PH响应 二硫键 缩醛键 药物控制释放 

分 类 号：O62[理学—有机化学]