Biodegradable Injectable Polymer Systems Exhibiting Temperature-Responsive Irreversible Sol-to-Gel Transition by Covalent Bond Formation

Biodegradable injectable polymer (IP) systems exhibiting temperature-responsive sol-to-gel transitions between room temperature and body temperature have the potential for use in biomedical applications. However, gelation of such IP systems is a reversible process through physical cross-linking, and the hydrogels thus formed are likely to revert to the sol state under highly wet conditions after injection. In this study, a biodegradable IP system exhibiting temperature responsive irreversible sol-to-gel transition by covalent bond formation was developed by simple mixing of polymers. A triblock copolymer of poly(caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG) and tri-PCG with attached succinimide ester groups at both termini (tri-PCG-SA-OSu) were prepared and mixed together with a water-soluble polyamine (typically poly-L-lysine). The obtained IP formulation was in the sol state after mixing, but exhibited a rapid sol-to-gel transition within 30 s upon increasing the temperature to 37 degrees C. Once formed, the hydrogel did not revert to the sol state, even after cooling to 4 degrees C, because of the formation of covalent bonds upon transition. The obtained hydrogel soaked in phosphate buffered saline (PBS) exhibited a significantly longer duration time of the gel state. This IP system exhibiting a rapid and irreversible sol-to-gel transition is convenient for medical professionals and possesses great potential for use in biomedical devices for clinical applications such as drug delivery systems and antiadhesive materials.