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
相关论文
共 34 条
[21]   Thermosensitive and biodegradable polymeric micelles for paclitaxel delivery [J].
Soga, O ;
van Nostrum, CF ;
Fens, M ;
Rijcken, CJF ;
Schiffelers, RM ;
Storm, G ;
Hennink, WE .
JOURNAL OF CONTROLLED RELEASE, 2005, 103 (02) :341-353
[22]   Physicochemical characterization of degradable thermosensitive polymeric micelles [J].
Soga, O ;
van Nostrum, CF ;
Ramzi, A ;
Visser, T ;
Soulimani, F ;
Frederik, PM ;
Bomans, PHH ;
Hennink, WE .
LANGMUIR, 2004, 20 (21) :9388-9395
[23]   Poly(N-(2-hydroxypropyl) methacrylamide mono/di lactate):: A new class of biodegradable polymers with tuneable thermosensitivity [J].
Soga, O ;
van Nostrum, CF ;
Hennink, WE .
BIOMACROMOLECULES, 2004, 5 (03) :818-821
[24]   A new approach to mineralization of biocompatible hydrogel scaffolds: An efficient process toward 3-dimensional bonelike composites [J].
Song, J ;
Saiz, E ;
Bertozzi, CR .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (05) :1236-1243
[25]   Biodegradable polymeric nanoparticles as drug delivery devices [J].
Soppimath, KS ;
Aminabhavi, TM ;
Kulkarni, AR ;
Rudzinski, WE .
JOURNAL OF CONTROLLED RELEASE, 2001, 70 (1-2) :1-20
[26]   SURFACE MODIFICATION OF NANOPARTICLES TO OPPOSE UPTAKE BY THE MONONUCLEAR PHAGOCYTE SYSTEM [J].
STORM, G ;
BELLIOT, SO ;
DAEMEN, T ;
LASIC, DD .
ADVANCED DRUG DELIVERY REVIEWS, 1995, 17 (01) :31-48
[27]  
Taillefer J, 2000, J PHARM SCI, V89, P52, DOI 10.1002/(SICI)1520-6017(200001)89:1<52::AID-JPS6>3.0.CO
[28]  
2-D
[29]   Thermosensitive micelle-forming block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) [J].
Topp, MDC ;
Dijkstra, PJ ;
Talsma, H ;
Feijen, J .
MACROMOLECULES, 1997, 30 (26) :8518-8520
[30]   Structure and design of polymeric surfactant-based drug delivery systems [J].
Torchilin, VP .
JOURNAL OF CONTROLLED RELEASE, 2001, 73 (2-3) :137-172