设计新型纳米乳-离子敏感型原位凝胶(nanoemulsion-in situ gel,NE-ISG),以氟比洛芬酯(flurbiprofen axetil,FBA)为模型药物,研究药物在家兔眼部的房水药动学特征,并对其流变学特征、微观形态、角膜损伤效果和角膜滞留特性等进行了评价。采用剪切均质工艺制备氟比洛芬酯纳米乳(flurbiprofen axetil nanoemulsion,FBA/NE),与离子敏感型凝胶材料(结冷胶)混合后制得氟比洛芬酯纳米乳-原位凝胶(flurbiprofen axetil nanoemulsion-in situ gel,FBA/NE-ISG)。流变学结果显示,FBA/NE-ISG发生胶凝后,黏度和弹性模量分别增加2Pa·s和5Pa,胶凝能力强。透射电镜结果表明,FBA/NE-ISG中乳滴粒度分布均匀,胶凝前后无明显变化。角膜损伤评价显示,FBA/NE-ISG无角膜刺激性。角膜滞留特性评价结果显示,NE-ISG角膜滞留时间显著延长,NE-ISG和溶液组的消除速率常数分别为0.0085min-1和0.1052min-1。房水药动学结果显示,FBA/NE-ISG组AUC0→12h(126.8μg·min·mL-1)和MRT(12.3h)分别是氟比洛芬钠滴眼液组(flurbiprofen sodium eye drop,FB-Na)的2.9倍和2.7倍,眼部生物利用度显著提高。FBA/NE-ISG能够显著延长药物的眼表滞留时间,发挥缓释作用,提高药物的眼部生物利用度,并有效降低原形药物氟比洛芬(flurbiprofen,FB)的眼部刺激性。 A novel nanoemulsion-in situ gel (NE-ISG) was designed and flurbiprofen axetil (FBA) was used as a model drug to study the aqueous humor Pharmacokinetic characteristics, and rheological characteristics, microscopic morphology, corneal damage and corneal retention characteristics were evaluated. The flurbiprofen axetil nanoemulsion (FBA / NE) was prepared by shear homogenization, and the flurbiprofen ester nanoemulsion was prepared by mixing with ion-sensitive gel material (gellan gum) Flurbiprofen axetil nanoemulsion-in situ gel (FBA / NE-ISG). Rheological results showed that the viscosity and elastic modulus of FBA / NE-ISG increased by 2 Pa · s and 5 Pa, respectively, with strong gelation ability. The results of TEM showed that the size distribution of emulsion droplets in FBA / NE-ISG was uniform and there was no obvious change before and after gelation. Corneal damage assessment showed no corneal irritation of FBA / NE-ISG. Corneal retention characteristics evaluation showed that the corneal retention time of NE-ISG was significantly prolonged, and the elimination rate constants of NE-ISG and solution group were 0.0085min-1 and 0.1052min-1, respectively. Aqueous humor pharmacokinetic results showed that the FAB / NE-ISG group AUC0 → 12h (126.8μg · min · mL-1) and MRT (12.3h) were flurbiprofen sodium eye drop group (flurbiprofen sodium eye drop, FB-Na) 2.9 times and 2.7 times, eye bioavailability significantly increased. FBA / NE-ISG can significantly prolong the ocular surface retention time, exert sustained release, improve the ocular bioavailability of drugs, and effectively reduce ocular irritation of the original drug flurbiprofen (FB).