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.
出处
《高分子学报》
SCIE
CAS
CSCD
北大核心
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
