Novel fast degradable thermosensitive polymeric micelles based on PEG-block-poly(N-(2-hydroxyethyl)methacrylamide-oligolactates)

被引:72
作者
Rijcken, CJF
Veldhuis, TFJ
Ramzi, A
Meeldijk, JD
van Nostrum, CF
Hennink, WE
机构
[1] Univ Utrecht, UIPS, Dept Pharmaceut, NL-3508 TB Utrecht, Netherlands
[2] Univ Utrecht, EMU, Dept Cell Biol, NL-3584 CH Utrecht, Netherlands
关键词
D O I
10.1021/bm0502720
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aim of this study was to design a thermosensitive polymeric micelle system with a relatively fast degradation time of around I day. These micelles are of interest for the (targeted) delivery of biologically active molecules. Therefore, N-(2-hydroxyethyl)methaci-ylamide-oligolactates (HEMAm-Lac(n)) were synthesized and used as building blocks for biodegradable (block co) polymers. p(HEMAm-Lac(2)) is a thermosensitive polymer with a cloud point (CP) of 22 degrees C which could be lowered by copolymerization with HEMAm-Lac(4). The block copolymer PEG-b-((80%HEMAm-Lac(2))-(20%HEMAm-Lac(4))) selfassembled into compact spherical micelles with an average size of 80 nm above the CP of the thermosensitive block (6 degrees C). Under physiological conditions (pH 7.4; 37 degrees C), the micelles started to swell after 4 h and were fully destabilized within 8 h due to hydrolysis of the lactate side chains. Rapidly degrading thermosensitive polymeric micelles based on PEG-b-((80%HEMAm-Lac(2))-(20%HEMAm-Lac(4))) have attractive features as a (targeted) drug carrier system for therapeutic applications.
引用
收藏
页码:2343 / 2351
页数:9
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