透明质酸修饰的栀子苷传递体凝胶的制备及其对佐剂型关节炎药效学评价  

Preparation of hyaluronic acid-modified geniposide transfersomes gels and its pharmacodynamic evaluation for adjuvant arthritis

作　　者：颜红[1] 高司琪 骆慧婷 欧阳威 王旭易 李爽 YAN Hong;GAO Si-qi;LUO Hui-ting;OUYANG Wei;WANG Xu-yi;LI Shuang(Hunan University of Chinese Medicine,Changsha 410208,China;Affiliated Hospital of Hunan Academy of Chinese Medicine,Changsha 410006,China;The Fourth Hospital of Changsha,Changsha 410006,China)

机构地区：[1]湖南中医药大学,湖南长沙410208 [2]湖南省中医药研究院附属医院,湖南长沙410006 [3]长沙市第四医院,湖南长沙410006

出　　处：《中草药》2023年第18期5867-5879,共13页Chinese Traditional and Herbal Drugs

基　　金：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)。

摘　　要：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。HAGTFs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 reversephase 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,HAGTFs 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 theζpotential 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 HAGTFs 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 g

关 键 词：栀子苷 透明质酸 传递体凝胶 Box-Behnken设计-响应面法 佐剂型关节炎 药效学 逆向旋转蒸法 肿瘤坏死因子-α 白细胞介素-6 

分 类 号：R283.6[医药卫生—中药学]