具有温敏性的混合胶束的制备与表征及药物体外释放  

PREPARATION AND CHARACTERIZATION OF THERMO-SENSITIVE MIXED MICELLES AND IN VITRO DRUG RELEASE

作　　者：谭松巍[1,2] 韩超[1] 王红军[1] 柳定荣[1] 涂克华[1] 蒋宏亮[1] 张梅华[3] 王利群[1] 

机构地区：[1]浙江大学高分子科学与工程学系高分子合成与功能构造教育部重点实验室,杭州310027 [2]华中科技大学同济药学院国家纳米药物工程技术研究中心,武汉430030 [3]浙江大学医学院附属第一医院药剂科,杭州310003

出　　处：《高分子学报》2011年第11期1237-1243,共7页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号21074112);华中科技大学校自主创新基金(基金号2010QN030)资助项目

摘　　要：通过原子转移自由基聚合(ATRP)合成了以胆固醇为端基的两亲性聚(N-异丙基丙烯酰胺)(Chol-PNIPAAm),利用FTIR、1H-NMR和GPC等方法表征了聚合物的结构.将该两亲性温敏聚合物与聚乙二醇单甲醚硬脂酸酯(mPEG-SA)通过简单混合,即可得到稳定的Chol-PNIPAAm/mPEG-SA混合胶束体系.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,Chol-PNIPAAm的胆固醇和mPEG-SA的硬脂酸共同构成了复合胶束的疏水内核,使得混合胶束具有更低的临界胶束浓度(CMC).动态光散射(DLS)研究表明,混合胶束不仅更稳定,而且具有温度响应性,其粒径在33～35℃之间可逆转变.药物体外释放结果表面,温度的升高会导致药物释放加快,PNIPAAm含量越高,释放速度越大.Amphiphilic poly（N-isopropylacrylamide） with cholesterol as hydrophobic end group（Chol-PNIPAM） was synthesized through atom transfer radical polymerization（ATRP）.The resulted Chol-PNIPAM was characterized with FTIR,1H-NMR and GPC.Simply mixing Chol-PNIPAM with methoxy poly（ethylene glycol） monostearate（mPEG-SA）,a mixed micellar system was prepared.The lower critical micellization concentration（CMC） of the mixed micelles was 6.23×10-3 g/L for the Chol/SA molar ratio of 0.2,and 1.00×10-2 g/L for the Chol/SA molar ratio of 0.5,respectively,which were significantly lower than that of the virgin mPEG-SA or Chol-PNIPAM micelles.Dynamic light scattering（DLS） study showed the composited micelle core was formed by cholesterol of Chol-PNIPAM and the fatty chain of mPEG-SA.The result is similar to the phenomenon that the cell membrane was stabilized by embedding cholesterol into the bilayer phospholipid membrane.DLS study also showed that the thermo-sensitive phase transition temperature expressed in the size change of the mixed micelles was between 33℃ and 35℃.The particle size of Chol-PNIPAM/mPEG-SA micelles with the Chol/SA molar ratio of 0.2 was 13 nm.When temperature was above 35℃,the size increased to 65 nm.For Chol-PNIPAM/mPEG-SA with the Chol/SA molar ratio of 0.5,the particle size changed from 14 nm to 200 nm,and the change was revisable.In contrast,the mPEG-SA micelles did not exhibit any temperature responsiveness,and the Chol-PNIPAM micelle,though thermal responsive,was not stable and large aggregation formed because of the hydrophilic-hydrophobic transition of PNIPAM segment.The results show that the Chol-PNIPAM/mPEG-SA mixed micelles with the properties of higher stability and satisfactory thermo-responsiveness is worth to study further for the use as a drug delivery system.In vitro release study shows that the release behavior of IMC from the drug-loaded micelle was thermo-sensitive and the release rate increases with both the PNIPAM content and temperature.

关 键 词：混合胶束 聚(N-异丙基丙烯酰胺) 胆固醇 聚乙二醇 药物释放 

分 类 号：O631.3[理学—高分子化学]