A Novel Thermoresponsive Gel as a Potential Delivery System for Lipoxin

The objective of this study was to evaluate a novel thermoresponsive polyisocyanopeptide (PIC)-based hydrogel as an injectable carrier for local drug delivery for periodontal applications. Three formulations of PIC gels, 0.2%, 0.5%, and 1% w/w, were prepared. As controls, commercially available poloxamer 407 (P407) gels of 20% and 26% w/w were used. Lipoxin A₄ (LXA₄), a proresolving drug, was suspended into the gel solutions. The systems were evaluated regarding dynamic mechanical properties, injectability and stability, release and bioactivity of LXA₄, and cytocompatibility. Results showed that the gelation temperatures of PIC and P407 gels were around 13°C to 23°C. PIC gels were less viscous and mechanically weaker than P407 gels due to the low polymer concentrations. However, PIC gels kept gel integrity for at least 2 wk when incubated with phosphate-buffered saline, whereas P407 gels were disintegrated totally within 1 wk. LXA₄ was chemically stable in both neutral and alkaline medium for over 1 mo. The release of LXA₄ from either 1% PIC or 26% P407 gels depicted an initial burst release followed by a sustained release for around 4 d. The extent of burst release was negatively correlated to the polymer concentration. LXA₄ remained bioactive after release from PIC gels. No cytotoxicity was observed for 1% PIC gel. However, 26% P407 inhibited periodontal ligament cell and gingival epithelial cell growth. In conclusion, the thermoresponsive PIC gel is a potential candidate for periodontal drug delivery.