新型聚乙二醇单酯复合胶束的制备及性能研究  

Novel MePEG-chol and MePEG-st Mixed Micellar Systems for Drug Delivery:Preparation and Characterization

作　　者：钱晓倩[1] 赖俊英[1,2] 詹树林[1] 张洁[2] 王利群[2] 涂克华[2] 

机构地区：[1]浙江大学建筑工程学院,浙江杭州310027 [2]浙江大学高分子科学研究所,浙江杭州310027

出　　处：《稀有金属材料与工程》2008年第A02期655-658,共4页Rare Metal Materials and Engineering

基　　金：国家自然科学基金资助(20474055)

摘　　要：以二环己基碳酰亚胺/N,N-二甲基氨基吡啶为偶联剂,酯化缩合了聚乙二醇单胆固醇酯(MePEG-chol)和聚乙二醇单硬脂酸酯(MePEG-st),并利用红外和核磁对产物结构进行了表征。采用表面张力法研究了MePEG-chol和MePEG-st溶液的胶束化行为。结果表明在MePEG-st的水溶液中加入MePEG-chol可以显著地降低MePEG-st溶液的临界胶束浓度(CMC)。当MePEG-chol和MePEG-st以0.2摩尔比混合时,形成的复合胶束体系的CMC最小,表明胶束体系最稳定。动态光散射及透射电子显微镜测试表明复合体系形成粒径在10nm左右,分布狭窄,形貌呈球形的微胶束粒子。与细胞膜中胆固醇通过嵌入磷脂疏水层达到稳定细胞膜的现象类似,本文中制备的MePEG-Chol中的胆固醇嵌入到MePEG-St的疏水脂肪层,构成了胶束中疏水的复合内核,从而提高了复合胶束的稳定性。By ester coupling reaction with dicyclohexyl carbodiimide/N, N＇-dimethyl amino pyridine as the active carboxyl group reagents, novel biomimetic micelles based on Methoxy poly（ethylene glycol）-cholesterol （MePEG-chol） and Methoxy poly（ethylene glycol）-stearic acid （MePEG-st） as amphiphilic polymer conjugates were prepared. Synthesized MePEG-chol and MePEG-st were confirmed by Fourier transform-infrared and nuclear magnetic resonance spectroscopy. Mixed miceUes with different molar ratio of the two conjugates were produced by a precipitation method. Critical micellization behavior was studied by surface tension measurement. The results showed that after introducing of MePEG-chol into MePEG-st aqueous solution, the CMC value of the system decreased remarkably comparing to MePEG-st aqueous solution. When the molar ratio of MePEG-chol and MePEG-st was 0.2, the micellar system was the most stable. The results of dynamic light scattering measurement and TEM observation indicated that the mixed systems form micelles in the size of 10 nm with a spherical morphology. The results showed that the mixed micelle was formed and the structure of the mixed miceUe was considered to be similar to cell membrane. This constructed biomimetic mixed micelle can be as a good candidate for the delivery of hydrophobic drugs.

关 键 词：聚合物胶束 胆固醇 硬脂酸 药物控释 

分 类 号：TQ460.1[化学工程—制药化工]