Biodegradable injectable polymer systems exhibiting a longer and controllable duration time of the gel state.

Here, we report biodegradable temperature-triggered covalent gelation systems exhibiting a longer and controllable duration time of the gel state by a "mixing strategy" utilizing a thiol-ene reaction. We synthesized a tri-block copolymer of poly(caprolactone-co-glycolic acid) and PEG (tri-PCG) as a temperature-responsive injectable polymer (IP) and attached acryloyl groups on both termini (tri-PCG-Acryl). A tri-PCG micelle solution containing hydrophobic hexa-functional polythiol (Solution-A) and a tri-PCG-Acryl micelle solution (Solution-B) were mixed together. After mixing, the solution was still in the sol state at r.t., but exhibited an irreversible sol-to-gel transition in response to temperature. The duration time of the gel state while soaking in PBS could be altered from 1 day to 93 days by changing the mixing ratio of Solution-A/B. The physical strengths of the hydrogels were also controllable by changing the mixing ratio. The IP system showed good biocompatibility and a long duration time of the gel state after subcutaneous implantation.

Injectable and biodegradable temperature-responsive mixed polymer systems providing variable gel-forming pH regions.

Aqueous solutions of biodegradable polymers exhibiting sol-to-gel transitions in response to external stimuli such as temperature and pH are expected to be used as injectable polymers (IPs) for biomedical applications. In this study, we prepared novel biodegradable temperature-responsive IP systems providing variable gel-forming pH regions. We synthesized PCGA-b-PEG-b-PCGA (tri-PCG) and attached carboxylic acid or primary amine groups on both termini, tri-PCG-COOH and tri-PCG-NH2, and investigated the temperature-responsive sol-to-gel transition behavior of the mixtures of these two copolymers at various pHs. We found that the gel-forming pH region of the mixed system could be easily controlled by simply changing the mixing ratios of these polymers.

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 °C. Once formed, the hydrogel did not revert to the sol state, even after cooling to 4 °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.