In periodontal treatment, topical adjunctive therapy with antimicrobials or anti-inflammatory agents is frequently applied. However, currently available drug carrier biomaterials often exhibit poor perfusion into small crevices, such as the deep and irregular periodontal pockets, due to relatively high viscosity. Moreover, high polymer concentrations of the polymer can potentially be cytotoxic upon confined local administration. This study aimed to formulate an antimicrobial and anti-inflammatory treatment option, by incorporating doxycycline (DOX) and/or lipoxin A₄ (LXA₄) into 0.5 wt% thermo-reversible polyisocyanopeptide (PIC). PIC can form hydrogels upon low polymer concentration, and we hypothesized that the thermo-reversible nature of the material would allow for application into the periodontal pocket. The formulations were characterized in vitro and finally tested in dogs with naturally occurring periodontitis, which were not euthanized afterward. Results showed that PIC/DOX/LXA₄ hydrogel could be easily prepared and injected into periodontal pockets. The PIC hydrogel facilitated the release of DOX or LXA₄ for around 4 days in vitro. When applied in dogs, the hydrogel exerted no local or systemic adverse effects. Gels loaded with LXA₄ and/or DOX reduced the subgingival bacterial load and pro-inflammatory interleukin-8 level. In addition, PIC-DOX and PIC-DOX+LXA₄ improved gingival clinical attachment by 0.6 mm compared with conventional periodontal treatment alone (i.e. mechanical debridement). In conclusion, the thermo-reversible PIC hydrogel is a safe and effective vehicle for periodontal drug delivery.

在牙周治疗中，经常使用抗微生物剂或抗炎剂进行局部辅助治疗。然而，由于相对较高的粘度，当前可用的药物载体生物材料经常表现出对小缝隙的不良灌注，所述小缝隙例如深的和不规则的牙周袋。此外，在局限的局部给药时，聚合物的高聚合物浓度可能具有细胞毒性。本研究旨在制定的抗微生物和抗炎治疗选择，通过将多西环素（DOX）和/或脂氧素甲₄（LXA ₄）转化为0.5 wt％的热可逆聚异氰基肽（PIC）。PIC可以在低聚合物浓度下形成水凝胶，我们假设该材料的热可逆特性使其可以应用于牙周袋中。对该制剂进行了体外表征，并最终在患有自然发生的牙周炎的狗中进行了测试，之后未对其实施安乐死。结果表明，PIC / DOX / LXA ₄水凝胶可以轻松制备并注射到牙周袋中。PIC水凝胶促进体外4天左右DOX或LXA ₄的释放。当在狗身上使用时，水凝胶不会产生局部或全身性副作用。装有LXA _4的凝胶和/或DOX降低了龈下细菌负荷和促炎性白细胞介素8水平。此外，与单独的常规牙周治疗（即机械清创术）相比，PIC-DOX和PIC-DOX + LXA ₄改善了0.6 mm的牙龈临床附着。总之，热可逆PIC水凝胶是用于牙周药物输送的安全有效的载体。