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 (11):1237-1243(2011)
DOI:
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 (11):1237-1243(2011) DOI: 10.3724/SP.J.1105.2011.10301.
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 6.2310-3 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.