口腔医学研究

口腔医学研究 ›› 2026, Vol. 42 ›› Issue (2): 134-140.DOI: 10.13701/j.cnki.kqyxyj.2026.02.009

• 牙周病学研究 • 上一篇    下一篇

基于载体分散技术的柚皮苷-盐酸小檗碱温敏凝胶对牙周炎治疗作用的体外研究

贾晔1, 宋继红1, 郑安祺1, 王艺斐1, 胡方方1, 刘若琳2, 卢闻1*   

  1. 1.西安交通大学医学部药学院 陕西 西安 710061;
    2.西安交通大学口腔医院,陕西省颅颌面精准医学研究重点实验室 陕西 西安 710061
  • 收稿日期:2025-06-23 发布日期:2026-02-28
  • 通讯作者: *卢闻,E-mail:lvlu2004@xjtu.edu.cn
  • 作者简介:贾晔(2001~ ),女,山西临汾人,硕士在读,研究方向:药剂学。
  • 基金资助:
    西安交通大学口腔医院“陕西省颅颌面精准医学研究重点实验室”开放课题资助项目(编号:2022LHM-KFKT003)

Therapeutic Potential of Naringin-berberine Hydrochloride Thermosensitive Gel Based on Carrier Dispersion Technology for Periodontitis in Vitro

JIA Ye1, SONG Jihong1, ZHENG Anqi1, WANG Yifei1, HU Fangfang1, LIU Ruolin2, LU Wen1*   

  1. 1. School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China;
    2. Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Hospital of Stomatology, Xi'an Jiaotong University. Xi'an 710061, China
  • Received:2025-06-23 Published:2026-02-28

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摘要： 目的: 探讨制备联合载药温敏凝胶用于牙周炎治疗的可行性。方法: 以载体分散技术制备柚皮苷的磷脂复合物、微球和微乳,在此基础上采用温敏原位凝胶技术联合盐酸小檗碱分别制备3种凝胶,对凝胶的外观、胶凝温度及时间、载药量、体外释药率、体外抑菌及细胞修复作用进行比较。结果: 3种温敏凝胶室温下均为黄色透明液体,可在37 ℃发生胶凝,其中微乳凝胶(naringin microemulsion-berberine gel, NM-BGel)的胶凝时间最短、载药量最高(每克凝胶载盐酸小檗碱和柚皮苷分别为0.98 mg和13.72 mg);体外释药考察中,两种试药呈分时段释放,盐酸小檗碱48 h释药率为80%,柚皮苷滞后释放,200 h可释药80%;NM-BGel对牙龈卟啉单胞菌(Porphyromonas gingivalis, P.gingivalis)具有抑制作用,可提高人牙周膜成纤维细胞(human periodontal ligament fibroblasts, hPDLFs)中碱性磷酸酶(alkaline phosphatase,ALP)活性,促进其增殖。结论: 基于微乳分散技术制备的联合载药温敏凝胶能够分时段释药,按时间序列依次发挥体外抗菌与促进细胞修复作用,为牙周炎的局部缓释给药系统进一步研究和牙周炎综合治疗提供了实验依据。

关键词: 柚皮苷, 盐酸小檗碱, 温敏凝胶, 牙周炎, 微乳

Abstract: Objective: To investigate the feasibility of thermosensitive gels with combined drug loading for the treatment of periodontitis. Methods: Phospholipid complexes, microspheres, and microemulsions of naringin were prepared using carrier dispersion technique. Subsequently, three thermosensitive in situ gels of naringin combined with berberine hydrochloride were prepared. The appearance, gelation temperature and time, drug loading capacity, in vitro drug release rate, antibacterial activity, and cell repair effects were compared. Results: All three thermosensitive gels were yellow transparent liquids at room temperature and gelled at approximately 37 ℃. The naringin microemulsion-berberine gel (NM-BGel) was demonstrated the shortest gelation time (57 s) and the highest drug loading capacity (0.98 mg for berberine hydrochloride and 13.72 mg for naringin). The drug release rate of berberine hydrochloride was 80% at 48 h, naringin was delayed and 80% at 200 h, which showed a time-segmented release mode. NM-BGel exhibited inhibitory effects on P. gingivalis and increased ALP activity in hPDLFs promoting their proliferation. Conclusion: The combined drug-loaded thermosensitive gel prepared based on microemulsion dispersion technology can achieve a time-segmented drug release and play antibacterial and cell repair functions in vitro over time. This provides experimental evidence for further research on local sustained drug delivery systems for periodontitis and comprehensive treatment of periodontitis.

Key words: naringin, berberine hydrochloride, thermosensitive gel, periodontitis, microemulsion