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

Branched poly(L-lactide)-poly(ethylene glycol) (PLLA-PEG) block copolymers were synthesized from trifunctional PLLA and amine functionalized methoxy poly(ethylene glycol)s. The copolymers in water formed hydrogels that showed thermo-responsive behavior. The hydrogels underwent a gel to sol transition with increasing temperature as determined with the vial tilting method and oscillatory rheology. For all copolymers, the transition temperature increased with increasing copolymer concentration. The transition temperature of corresponding branched copolymers also increased with increasing PEG molecular weight, and surprisingly decreased with increasing molecular weight of the PLLA branches. In general, the gel-sol transition is explained by disruption of micellar or aggregate interactions because of partial dehydration and shrinkage of the PEG chains. An increase in the molecular weight of the PLLA branches led to the formation of micelles and aggregates as observed with DLS at low concentrations. It is speculated that the non-uniform size distribution and possible crystallization of longer PLLA blocks may have a negative effect on the formation of micellar packing upon gelation, allowing the disruption of micellar or aggregate interactions to occur at lower temperatures. The transition temperature of the gels could be tuned closely to body temperature by varying the concentration of the solution or the molecular weight of the PEG block and the PLLA blocks, which implies that these polymers may be used as injectable systems for in-situ gel formation.