目的 制备基于氨基酸的低共熔凝胶敷料，对其体外性能及体内治疗口腔溃疡药效作用进行研究。方法 以赖氨酸、脯氨酸、精氨酸、甘氨酸为氢键供体，乳酸、柠檬酸、甘油、甘露醇、苹果酸为氢键受体，制备筛选低共熔溶剂（deep eutectic solvent，DES），以姜黄素溶解度为指标确定最优体系。基于甲基丙烯酰化明胶/甲基丙烯酰化壳聚糖（gelatin methacryloyl/chitosan methacryloyl，GelMA/CSMA）复合基质，结合3D打印技术优化处方工艺制备凝胶敷料，评价其机械性能、黏附性、溶胀特性和生物相容性，并构建SD大鼠口腔溃疡模型验证体内疗效。结果 最优DES体系（脯氨酸-乳酸1∶12）对姜黄素的增溶能力达0.789 mg/mL，较水中溶解度提升700余倍。最优打印处方和工艺参数分别为1% CSMA-5% GelMA，0.1%苯基-2,4,6-三甲基苯甲酰基膦酸锂（lithium phenyl-2,4,6-trimethylbenzoylphosphinate，LAP），0.02%柠檬黄，20% DES添加量，100 μm打印层高，25 s逐层曝光时间。所得氨基酸基凝胶敷料机械性能优异，黏附力25 min达2.5 N，6 h溶胀率约500%。体外生物相容性显示，L929细胞存活率均＞90%，DES体系无显著细胞毒性；SD大鼠口腔溃疡模型中，该凝胶可局部缓释姜黄素，使溃疡面积较对照组减少40%，并有效降低中性粒细胞密度及炎症浸润程度。结论 成功制备负载姜黄素的氨基酸基DES凝胶敷料，具有良好的伤口适配性与精准药物释放行为，为口腔溃疡提供了高效、安全的治疗策略。

Objective To prepare an amino acid-based deep eutectic gel dressing and study in vitro performance and the in vivo therapeutic effect on oral ulcer. Methods Deep eutectic solvents (DESs) were screened using lysine, proline, arginine, and glycine as hydrogen bond donors, and lactic acid, citric acid, glycerol, mannitol, and malic acid as acceptors, with curcumin solubility identifying the optimal system. Gel dressings were prepared by optimizing the formulation process based on the composite matrix of gelatin methacryloyl/chitosan methacryloyl (GelMA/CSMA) in combination with 3D printing technology. Its mechanical properties, adhesiveness, swelling, and biocompatibility were evaluated, and in vivo efficacy was verified in an SD rat oral ulcer model. Results The optimal DES system (proline-lactic acid, 1:12) increased curcumin solubility over 700-fold (0.789 mg/mL) compared to its solubility in water. The optimal printing formulation and process parameters were as follows: 1% CSMA, 5% GelMA, 0.1% lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), 0.02% tartrazine, 20% DES content, 100 μm layer height, and a layer-by-layer exposure time of 25 s. The obtained amino acid-based gel dressing had excellent mechanical properties, with a 2.5 N adhesion force at 25 min and an approximately 500% swelling ratio at 6 h. In vitro biocompatibility showed that the survival rate of L929 cells was all above 90%, and the DES system had no significant cytotoxicity. It also showed high in vitro biocompatibility (L929 viability > 90%, non-cytotoxic). In vivo, the gel achieved localized, sustained curcumin release in SD oral ulcer model rats, reducing ulcer area by 40% with decreased neutrophil density and inflammatory infiltration. Conclusion Successfully prepared an amino acid-based DES gel dressing loaded with curcumin, which exhibits excellent wound adaptability and precise drug release behavior, offering an efficient and safe therapeutic strategy for oral ulcers.

R283.6

湖州市科技局公益研究项目—人口健康类（2025GY121）；浙江省中医药科技计划项目资助（2025ZL027）