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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. 浙江大学医学院附属第一医院药剂科,杭州,310003
纸质出版日期:2011-11-20,
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谭松巍, 韩超, 王红军, 柳定荣, 涂克华, 蒋宏亮, 张梅华, 王利群. 具有温敏性的混合胶束的制备与表征及药物体外释放[J]. 高分子学报, 2011,(11):1237-1243.
TAN Songwei, HAN Chao, WANG Hongjun, LIU Dingrong, TU Kehua, JIANG Hongliang, ZHANG Meihua, WANG Li-qun. PREPARATION AND CHARACTERIZATION OF THERMO-SENSITIVE MIXED MICELLES AND IN VITRO DRUG RELEASE[J]. Acta Polymerica Sinica, 2011,(11):1237-1243.
谭松巍, 韩超, 王红军, 柳定荣, 涂克华, 蒋宏亮, 张梅华, 王利群. 具有温敏性的混合胶束的制备与表征及药物体外释放[J]. 高分子学报, 2011,(11):1237-1243. DOI: 10.3724/SP.J.1105.2011.10301.
TAN Songwei, HAN Chao, WANG Hongjun, LIU Dingrong, TU Kehua, JIANG Hongliang, ZHANG Meihua, WANG Li-qun. PREPARATION AND CHARACTERIZATION OF THERMO-SENSITIVE MIXED MICELLES AND IN VITRO DRUG RELEASE[J]. Acta Polymerica Sinica, 2011,(11):1237-1243. DOI: 10.3724/SP.J.1105.2011.10301.
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 6.2310-3 g/L for the Chol/SA molar ratio of 0.2
and 1.0010-2 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.
混合胶束聚(N-异丙基丙烯酰胺)胆固醇聚乙二醇药物释放
Mixed micellePNIPAAmCholesterolPEGIn vitro release
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