Novel fast degradable thermosensitive polymeric micelles based on PEG-block-poly(N-(2-hydroxyethyl)methacrylamide-oligolactates).
The aim of this study was to design a thermosensitive polymeric micelle system with a relatively fast degradation time of around 1 day. These micelles are of interest for the (targeted) delivery of biologically active molecules. Therefore, N-(2-hydroxyethyl)methacrylamide-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))) self-assembled 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.
Rijcken
Cristianne J F
CJ
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80.082, 3508TB, Utrecht, The Netherlands.
Veldhuis
Theo F J
TF
Ramzi
Aissa
A
Meeldijk
Johannes D
JD
van Nostrum
Cornelus F
CF
Hennink
Wim E
WE
D002850:Chromatography, Gel; D006868:Hydrolysis; D007700:Kinetics; D007773:Lactates / Q000737:chemistry*; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*
D007773:Lactates; D008823:Micelles; D011108:Polymers; D011109:Polymethacrylic Acids; D011092:Polyethylene Glycols; C011533:Duxon