Thermo-sensitive and biodegradable hydrogels based on stereocomplexed Pluronic multi-block copolymers for controlled protein delivery

Injectable sol-gel transition hydrogels based on thermo-sensitive polymers are of great interest as potential biomaterials for sustained delivery of therapeutic molecules. A novel temperature-sensitive and in-situ forming hydrogel system based on Pluronic F127 was developed and evaluated. A series of multi-block Pluronic copolymers linked by d-lactide and l-lactide oligomers with different spacer lengths were synthesized. A pair of multi-block copolymers having the corresponding enantiomeric d- or l-lactide oligomer spacer was blended to form stereocomplexed hydrogels. The resultant physically crosslinked Pluronic hydrogels exhibited significantly altered sol-gel phase transition behaviors with much lower critical gelation concentrations and temperatures, compared to the uncomplexed multi-block or Pluronic homopolymer hydrogels. The stereocomplexed hydrogels also had far increased mechanical strength with high resistance to rapid dissolution in aqueous medium. When human growth hormone (hGH) was incorporated in the strereocomplexed multi-block Pluronic copolymers, hGH was released out in a sustained and zero-order fashion for 13 days by a diffusion/erosion coupled mechanism.