1 Department of Biomaterials, Radboud University Medical Centre, Nijmegen, the Netherlands.
J Dent Res. 2019 Mar;98(3):355-362. doi: 10.1177/0022034518810213. Epub 2018 Nov 7.
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 A (LXA), a proresolving drug, was suspended into the gel solutions. The systems were evaluated regarding dynamic mechanical properties, injectability and stability, release and bioactivity of LXA, 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. LXA was chemically stable in both neutral and alkaline medium for over 1 mo. The release of LXA 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. LXA 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.
本研究旨在评估一种新型温敏聚异氰酸酯肽（PIC）基水凝胶作为局部给药的可注射载体，用于牙周应用。制备了三种 PIC 凝胶配方，即 0.2%、0.5%和 1%w/w。作为对照，使用了市售的 20%和 26%w/w的泊洛沙姆 407（P407）凝胶。将脂氧素 A（LXA），一种促解决药物，混悬于凝胶溶液中。对系统的动态力学性能、可注射性和稳定性、LXA 的释放和生物活性以及细胞相容性进行了评价。结果表明，PIC 和 P407 凝胶的胶凝温度约为 13°C 至 23°C。由于聚合物浓度较低，PIC 凝胶的粘度和机械强度均低于 P407 凝胶。然而，当 PIC 凝胶在磷酸盐缓冲液中孵育时，其凝胶完整性至少可维持 2 周，而 P407 凝胶在 1 周内完全崩解。LXA 在中性和碱性介质中化学稳定超过 1 个月。LXA 从 1%PIC 或 26%P407 凝胶中的释放呈现出初始突释，随后持续释放约 4 天。突释程度与聚合物浓度呈负相关。LXA 从 PIC 凝胶释放后仍保持生物活性。1%PIC 凝胶无细胞毒性。然而，26%P407 抑制牙周韧带细胞和牙龈上皮细胞的生长。总之，温敏 PIC 凝胶是一种有潜力的牙周给药载体。
