尼非韦罗阴道温敏原位凝胶的流变学研究

Rheological characteristics of nifeviroc vaginal thermosensitive in situ gels

目的:应用动态流变实验测定温度敏感型原位凝胶的流变性质,以预测其在体胶凝(相变)行为。方法:通过处方筛选,确定以泊洛沙姆407和188作为基质,制备尼非韦罗阴道温敏原位凝胶(NFVR-TISG)。通过差示扫描热量法(DSC)测定NFVR-TISG胶凝温度。采用动态流变学实验测定NFVR-TISG在不同温度下相变过程中的流变参数,及NFVR-TISG经模拟阴道夜稀释(5∶1)后的流变参数。结果:NFVR-TISG在室温条件下为黏弹性较低的牛顿流体,温度升至29℃时形成凝胶状态;相变行为表现为黏弹性呈指数增长,相角降低;流变学结果显示的胶凝温度与DSC结果(30.4℃)基本一致;模拟阴道液稀释后NFVR-TISG约在35℃发生相转变。结论:体外流变学特点显示NFVR-TISG符合临床阴道局部用药物要求。用于体外评价的动态流变学实验可反映温敏凝胶的黏弹性流体力学特点。

Objective ： To characterize the rheological properties of thermosensitive in situ gels for predicting the behaviors of thermal gelation, nethods：Nifeviroc vaginal thermosensitive in situ gel （NFVR-TISG） was pre- pared using poloxamer407 and poloxamer188 as the gel matrix. Rheological parameters of NFVR-TISG and the NFVR-TISG diluted by stimulant vaginal fluid （SVF） were measured during phase transition at different tempera- tures,and gelation temperature was estimated by differential scanning calorimeter （DSC）. Results： NFVR-TISG was Newtonian fluid with low viscoelasticity under room temperature and was converted to gel at 29 ℃. With the in- crease of temperature,the sol-gel transition process showed exponential increase and the phase angle showed de- crease. The gelation temperature of NFVR-TISG detected by DSC was 30.4 ℃ , similar to that measured by dynamic rheological studies. Conclusion ：The rheological properties of NFVR-TISG meet the requirements for vaginal topical use. Dynamic rheological experiment may provide useful information for further in vitro evaluation of viscoelastic hy- drodynamic properties of thermosensitive in situ gel.