Thermo-responsive hydrogels based on highly branched poly(ethylene glycol)-poly(L-lactide) copolymers

Highly branched poly(ethylene glycol)-poly(L-lactide) (PEG-PLLA) copolymers were synthesized by a coupling reaction of eight-arm amine-functionalized PEG and macromonomers having 2 PLLA arms and a N-hydroxysuccinimide activated ester group at the branching point. A coupling efficiency of approximately 50% was achieved. Copolymer solutions in water (>= 4 wt.%) showed a phase transition from gel to sol upon increasing the temperature. The critical gelation concentration at 20 degrees C decreased with increasing PLLA block length. The gel-sol transition of a 12 wt.% aqueous copolymer solution increased from 4 degrees C for a copolymer with PLLA blocks with 3 repeating lactide units per arm to 38 degrees C for a copolymer with PLLA blocks with 5 repeating lactide units per arm. Furthermore, the gel-sol transition temperature increased with increasing copolymer concentration, and could be tuned closely to body temperature, which makes these hydrogels interesting as injectable systems for in situ gel formation. (C) 2010 Elsevier Ltd. All rights reserved.