目的 制备透明质酸修饰的栀子苷传递体（hyaluronic acid modified geniposide transfersomes，HA-GTFs）凝胶，对其进行质量评价，并考察其治疗大鼠佐剂型关节炎的疗效。方法 采用逆向旋转蒸法制备HA-GTFs，通过单因素与Box-Behnken设计-响应面法筛选处方及制备工艺，并比较了其与透明质酸修饰的栀子苷脂质体（hyaluronic acid modified geniposide lipsomes，HA-GLIPs）的变形性。在此基础上，制备了HA-GTFs凝胶，考察了其黏度、稳定性、体外释放及体外透皮性能，并进行佐剂型关节炎的初步药效学评价。结果 透射电子显微镜下，HA-GTFs呈规则的球形，结构完整，分散均匀。HA-GTFs包封率为57.38%，平均粒径为（117.53±0.83）nm，ζ电位为（−8.53±0.76）mV，且其变形性优于HA-GLIPs。体外释放试验结果表明，普通栀子苷凝胶在12 h时释放完全，HA-GLIPs凝胶与HA-GTFs凝胶表现出缓释的效果，48 h累积释放率分别为92%、89%。体外透皮试验结果显示，HA-GTFs凝胶在24 h内的累积透皮率高于HA-GLIPs凝胶与普通栀子苷凝胶，表明传递体凝胶具有良好的透皮性能。初步药效学实验显示，与模型组相比，HA-GTFs凝胶组能减轻大鼠炎症反应，病理切片未见大量炎症细胞浸润，且能降低血清炎症因子肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）与白细胞介素-6（interleukin-6，IL-6）水平。其中HA-GTFs凝胶高剂量组的治疗效果显著优于其他组。结论 HA-GTFs凝胶的处方工艺简单、稳定，具有良好的缓释与透皮性能，对佐剂型关节炎具有一定的治疗效果。

Objective To prepare the hyaluronic acid modified geniposide transfersomes (HA-GTFs) gels, evaluate the quality of the gels, and investigate its therapeutic effects on adjuvant arthritis in rats. Methods The HA-GTFs formulation was prepared by reverse-phase evaporation and screened by single-factor and Box-Behnken design-response surface method to acquire the best prescription. The elasticity comparison of HA-GTFs and hyaluronic acid modified geniposide liposomes (HA-GLIPs) was done. On this basis, HA-GTFs gels were prepared. The viscosity, stability, release properties and percutaneous permeability in vitro of HA-GTFS gels were measured, and the preliminary pharmacodynamic evaluation of HA-GTFS gels was conducted. Results Under the transmission electron microscope, the HA-GTFs was in a regular spherical shape with complete structure and uniform dispersion. The HA-GTFs were successfully prepared with an encapsulation efficiency of 57.38%. The average particle size was (117.53 ± 0.83) nm, and the ζ potential was (−8.53 ± 0.76) mV, and the deformability of HA-GTFS was better than that of HA-GLIPs. In vitro release test showed that common geniposide gels released completely at 12 h, and HA-GLIPs and HA-GTFs gels showed sustained release effects, with cumulative release rates of 92% and 89% at 48 h, respectively. In vitro transdermal test showed that the cumulative transdermal rate of HA-GTFs gels was higher than those of HA-GLIPs gels and common geniposide gels within 24 h, indicating that the transdermal properties of the HA-GTFs gels were good. In vivo pharmacodynamic studies showed that compared with the model group, the HA-GTFs gels groups could reduce the inflammatory response of rats, and reduce the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), without large number of inflammatory cell infiltration in pathological sections. Among them, the therapeutic effects of high-dose HA-GTFs gels group were significantly better than others. Conclusion The formulation process of HA-GTFs gels is simple and stable. The HA-GTFs gels have good sustained release and transdermal performance, with a certain therapeutic effect on adjuvant arthritis.

R283.6

湖南省自然科学基金面上项目（2022JJ30444）；湖南中医药大学重点学科中药学科（校行发规字［2023］2号）；湖南省中医药科研计划项目（2021223）