具有温敏性的混合胶束的制备与表征及药物体外释放

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....

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

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.